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\n \n 2024\n \n \n (47)\n \n \n

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\n \n\n \n \n \n \n \n \n Genetic Variability in Parkinson's Disease: A2M Gene Mutations Examined in a Cohort of 179 Patients with Familial and Early-Onset Forms.\n \n \n \n \n\n\n \n Scanni, M. D.; Janes, F.; Bernardini, A.; Ermanis, G.; and Valente, M.\n\n\n \n\n\n\n Parkinsonism & Related Disorders, 122. May 2024.\n Publisher: Elsevier\n\n\n\n
\n\n\n\n \n \n $\"Genetic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{scanni_genetic_2024,\n\ttitle = {Genetic {Variability} in {Parkinson}'s {Disease}: {A2M} {Gene} {Mutations} {Examined} in a {Cohort} of 179 {Patients} with {Familial} and {Early}-{Onset} {Forms}},\n\tvolume = {122},\n\tissn = {1353-8020, 1873-5126},\n\tshorttitle = {Genetic {Variability} in {Parkinson}'s {Disease}},\n\turl = {https://www.prd-journal.com/article/S1353-8020(24)00123-8/abstract},\n\tdoi = {10.1016/j.parkreldis.2024.106111},\n\tlanguage = {English},\n\turldate = {2024-05-06},\n\tjournal = {Parkinsonism \\& Related Disorders},\n\tauthor = {Scanni, M. D. and Janes, F. and Bernardini, A. and Ermanis, G. and Valente, M.},\n\tmonth = may,\n\tyear = {2024},\n\tnote = {Publisher: Elsevier},\n\tkeywords = {CES, Clinical Exome, Cohort, Neurodegenerative Diseases, Parkinson’s disease, clinical exome sequencing (CES)},\n}\n\n

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\n \n\n \n \n \n \n \n \n The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression.\n \n \n \n \n\n\n \n Medina-Herrera, A.; Vazquez, I.; Cuenca, I.; Rosa-Rosa, J. M.; Ariceta, B.; Jimenez, C.; Fernandez-Mercado, M.; Larrayoz, M. J.; Gutierrez, N. C.; Fernandez-Guijarro, M.; Gonzalez-Calle, V.; Rodriguez-Otero, P.; Oriol, A.; Rosiñol, L.; Alegre, A.; Escalante, F.; De La Rubia, J.; Teruel, A. I.; De Arriba, F.; Hernandez, M. T.; Lopez-Jimenez, J.; Ocio, E. M.; Puig, N.; Paiva, B.; Lahuerta, J. J.; Bladé, J.; San Miguel, J. F.; Mateos, M. V.; Martinez-Lopez, J.; Calasanz, M. J.; and Garcia-Sanz, R.\n\n\n \n\n\n\n Blood Cancer Journal, 14(1): 1–11. April 2024.\n Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"The$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{medina-herrera_genomic_2024,\n\ttitle = {The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression},\n\tvolume = {14},\n\tcopyright = {2024 The Author(s)},\n\tissn = {2044-5385},\n\turl = {https://www.nature.com/articles/s41408-024-01053-3},\n\tdoi = {10.1038/s41408-024-01053-3},\n\tabstract = {Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2024-05-01},\n\tjournal = {Blood Cancer Journal},\n\tauthor = {Medina-Herrera, A. and Vazquez, I. and Cuenca, I. and Rosa-Rosa, J. M. and Ariceta, B. and Jimenez, C. and Fernandez-Mercado, M. and Larrayoz, M. J. and Gutierrez, N. C. and Fernandez-Guijarro, M. and Gonzalez-Calle, V. and Rodriguez-Otero, P. and Oriol, A. and Rosiñol, L. and Alegre, A. and Escalante, F. and De La Rubia, J. and Teruel, A. I. and De Arriba, F. and Hernandez, M. T. and Lopez-Jimenez, J. and Ocio, E. M. and Puig, N. and Paiva, B. and Lahuerta, J. J. and Bladé, J. and San Miguel, J. F. and Mateos, M. V. and Martinez-Lopez, J. and Calasanz, M. J. and Garcia-Sanz, R.},\n\tmonth = apr,\n\tyear = {2024},\n\tnote = {Publisher: Nature Publishing Group},\n\tkeywords = {Clinical genetics, Custom, Custom Cancer Panel, Custom Panel, DDM, Risk factors},\n\tpages = {1--11},\n}\n\n

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\n \n\n \n \n \n \n \n \n Alzheimer Disease Associated Loci: APOE Single Nucleotide Polymorphisms in Marmara Region.\n \n \n \n \n\n\n \n Ismail, A. B.; Dundar, M. S.; Erguzeloglu, C. O.; Ergoren, M. C.; Alemdar, A.; Ozemri Sag, S.; and Temel, S. G.\n\n\n \n\n\n\n Biomedicines, 12(5): 968. April 2024.\n Number: 5 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Alzheimer$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{ismail_alzheimer_2024,\n\ttitle = {Alzheimer {Disease} {Associated} {Loci}: {APOE} {Single} {Nucleotide} {Polymorphisms} in {Marmara} {Region}},\n\tvolume = {12},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2227-9059},\n\tshorttitle = {Alzheimer {Disease} {Associated} {Loci}},\n\turl = {https://www.mdpi.com/2227-9059/12/5/968},\n\tdoi = {10.3390/biomedicines12050968},\n\tabstract = {Alzheimer’s disease (AD) is a major global health challenge, especially among individuals aged 65 or older. According to population health studies, Turkey has the highest AD prevalence in the Middle East and Europe. To accurately determine the frequencies of common and rare APOE single nucleotide polymorphisms (SNPs) in the Turkish population residing in the Marmara Region, we conducted a retrospective study analyzing APOE variants in 588 individuals referred to the Bursa Uludag University Genetic Diseases Evaluation Center. Molecular genotyping, clinical exome sequencing, bioinformatics analysis, and statistical evaluation were employed to identify APOE polymorphisms and assess their distribution. The study revealed the frequencies of APOE alleles as follows: ε4 at 9.94\\%, ε2 at 9.18\\%, and ε3 at 80.68\\%. The gender-based analysis in our study uncovered a tendency for females to exhibit a higher prevalence of mutant genotypes across various SNPs. The most prevalent haplotype observed was ε3/ε3, while rare APOE SNPs were also identified. These findings align with global observations, underscoring the significance of genetic diversity and gender-specific characteristics in comprehending health disparities and formulating preventive strategies.},\n\tlanguage = {en},\n\tnumber = {5},\n\turldate = {2024-04-29},\n\tjournal = {Biomedicines},\n\tauthor = {Ismail, Aya Badeea and Dundar, Mehmet Sait and Erguzeloglu, Cemre Ornek and Ergoren, Mahmut Cerkez and Alemdar, Adem and Ozemri Sag, Sebnem and Temel, Sehime Gulsun},\n\tmonth = apr,\n\tyear = {2024},\n\tnote = {Number: 5\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {APOE gene, Alzheimer’s disease, CES, Clinical Exome Solution, DDM, Turkish population, clinical exome sequencing, variant frequency},\n\tpages = {968},\n}\n\n

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\n \n\n \n \n \n \n \n Evaluation of an Updated Gene Panel as a Diagnostic Tool for Both Male and Female Infertility.\n \n \n \n\n\n \n Okutman, Ö.; Gürbüz, A. S.; Salvarci, A.; Büyük, U.; Ruso, H.; Gürgan, T.; Tarabeux, J.; Leuvrey, A.; Nourisson, E.; Lang, C.; Muller, J.; and Viville, S.\n\n\n \n\n\n\n Reproductive Sciences (Thousand Oaks, Calif.). April 2024.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{okutman_evaluation_2024,\n\ttitle = {Evaluation of an {Updated} {Gene} {Panel} as a {Diagnostic} {Tool} for {Both} {Male} and {Female} {Infertility}},\n\tissn = {1933-7205},\n\tdoi = {10.1007/s43032-024-01553-4},\n\tabstract = {In recent years, an increasing number of genes associated with male and female infertility have been identified. The genetics of infertility is no longer limited to the analysis of karyotypes or specific genes, and it is now possible to analyse several dozen infertility genes simultaneously. Here, we present the diagnostic activity over the past two years including 140 patients (63 women and 77 men). Targeted sequencing revealed causative variants in 17 patients, representing an overall diagnostic rate of 12.1\\%, with prevalence rates in females and males of 11\\% and 13\\%, respectively. The gene-disease relationship (GDR) was re-evaluated for genes due to the addition of new patients and/or variants in the actual study. Five genes changed categories: two female genes (MEIOB and TBPL2) moved from limited to moderate; two male genes (SOHLH1 and GALNTL5) moved from no evidence to strong and from limited to moderate; and SEPTIN12, which was unable to classify male infertility, was reclassified as limited. Many infertility genes have yet to be identified. With the increasing integration of genetics in reproductive medicine, the scope of intervention extends to include other family members, in addition to individual patients or couples. Genetic counselling consultations and appropriate staffing will need to be established in fertility centres. Trial registration number: Not applicable.},\n\tlanguage = {eng},\n\tjournal = {Reproductive Sciences (Thousand Oaks, Calif.)},\n\tauthor = {Okutman, Özlem and Gürbüz, Ali Sami and Salvarci, Ahmet and Büyük, Umut and Ruso, Halil and Gürgan, Timur and Tarabeux, Julien and Leuvrey, Anne-Sophie and Nourisson, Elsa and Lang, Cécile and Muller, Jean and Viville, Stephane},\n\tmonth = apr,\n\tyear = {2024},\n\tpmid = {38664359},\n\tkeywords = {Alamut, Alamut Batch, Alamut Batch v1.11, Female infertility, Gene panel, Male infertility, Reproductive genetics},\n}\n\n

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\n\n\n

\n \n\n \n \n \n \n \n \n A Recurrent c.416C-T Variant in the B3GAT3 Gene in the Turkish Population: Report of Two Siblings and Expanding the Clinical Spectrum.\n \n \n \n \n\n\n \n Daşar, T.; Kolkıran, A.; Sezer, A.; Bal, E.; and Kılıç, E.\n\n\n \n\n\n\n Molecular Syndromology,1–12. April 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{dasar_recurrent_2024,\n\ttitle = {A {Recurrent} c.{416C}-{T} {Variant} in the {B3GAT3} {Gene} in the {Turkish} {Population}: {Report} of {Two} {Siblings} and {Expanding} the {Clinical} {Spectrum}},\n\tissn = {1661-8769},\n\tshorttitle = {A {Recurrent} c.{416C}{\\textgreater}{T} {Variant} in the {B3GAT3} {Gene} in the {Turkish} {Population}},\n\turl = {https://doi.org/10.1159/000537869},\n\tdoi = {10.1159/000537869},\n\tabstract = {Introduction: Linkeropathies are a group of rare multi-systemic genetic disorders primarily affecting the skeletal and cardiac systems due to defects in the enzymes responsible for proteoglycan synthesis. Case Presentation: We present a case of two siblings with the B3GAT3 variant. The 14-year-old boy exhibited short stature, severe kyphoscoliosis, splenomegaly, and aortic root dilatation, along with several physical abnormalities including bifid uvula, blue sclera, limited elbow extension, and pectus carinatum. His 6-year-old sister also exhibited comparable yet less pronounced physical features. Clinical exome sequencing analysis revealed a homozygous c.416C\\&gt;T variant in the B3GAT3 gene for the sister; the same variant was also present in the boy patient. The boy underwent preoperative halo-gravity traction for severe kyphoscoliosis, followed by posterior instrumentation and fusion surgery without complications. Discussion/Conclusion: B3GAT3-related linkeropathy syndrome is a rare disorder and we further expand the clinical spectrum with novel findings.},\n\turldate = {2024-04-24},\n\tjournal = {Molecular Syndromology},\n\tauthor = {Daşar, Tuğba and Kolkıran, Abdulkerim and Sezer, Abdullah and Bal, Ercan and Kılıç, Esra},\n\tmonth = apr,\n\tyear = {2024},\n\tkeywords = {Aortic root dilatation, B3GAT3, CES v3, DDM, Kyphoscoliosis, Linkeropathy, Radio-ulnar synostosis, clinical exome sequencing (CES)},\n\tpages = {1--12},\n}\n\n

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\n \n\n \n \n \n \n \n \n A 37-kb Deletion in Region 16p13.3 in an Infant with Osteopetrosis and Congenital Diarrhea Including the CLCN7 and PERCC1 Genes.\n \n \n \n \n\n\n \n Sandal, S.; Kayhan, G.; Kahvecioglu, D.; Vezir, E.; Kilic, A.; Köse, A.; Tas Ersun, M.; Derme, T.; Bahap, Y.; Dereci, S.; and Hizli, S.\n\n\n \n\n\n\n Molecular Syndromology,1–5. April 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{sandal_37-kb_2024,\n\ttitle = {A 37-kb {Deletion} in {Region} 16p13.3 in an {Infant} with {Osteopetrosis} and {Congenital} {Diarrhea} {Including} the {CLCN7} and {PERCC1} {Genes}},\n\tissn = {1661-8769},\n\turl = {https://doi.org/10.1159/000538395},\n\tdoi = {10.1159/000538395},\n\tabstract = {Introduction: Congenital diarrhea presents a diagnostic challenge in cases where standard assessments are inconclusive. Case Presentation: We report a female infant with thrombocytopenia, increased bone density, and pale optic disc symptoms, suggestive of osteopetrosis. However, she also exhibited noninfectious, blood- and mucus-free diarrhea, not accounted for by osteopetrosis. Genetic testing, including clinical exome sequencing and chromosomal microarray analysis, revealed a homozygous 39-kb deletion on chromosome 16p13.3. This deletion spanned the CLCN7 gene associated with osteopetrosis and the PERCC1 gene implicated in congenital diarrhea. Conclusion: This case illustrates the importance of considering 16p13.3 deletions when confronted with the dual presentation of congenital diarrhea and osteopetrosis, expanding the diagnostic considerations for similar clinical presentations.},\n\turldate = {2024-04-22},\n\tjournal = {Molecular Syndromology},\n\tauthor = {Sandal, Semih and Kayhan, Gulsum and Kahvecioglu, Dilek and Vezir, Emine and Kilic, Ayse and Köse, Aslihan and Tas Ersun, Melda and Derme, Turan and Bahap, Yusuf and Dereci, Selim and Hizli, Samil},\n\tmonth = apr,\n\tyear = {2024},\n\tkeywords = {16p13.3 deletion, CES v2, CLCN7, Congenital diarrhea, DDM, Osteopetrosis, PERCC1, clinical exome sequencing (CES)},\n\tpages = {1--5},\n}\n\n

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\n \n\n \n \n \n \n \n \n Genome-wide analysis identifies MYH11 compound heterozygous variants leading to visceral myopathy corresponding to late-onset form of megacystis-microcolon-intestinal hypoperistalsis syndrome.\n \n \n \n \n\n\n \n Billon, C.; Piccoli, G. B.; de Sainte Agathe, J.; Stoeva, R.; Derive, N.; Heidet, L.; Berrebi, D.; Bruneval, P.; Jeunemaitre, X.; and Hureaux, M.\n\n\n \n\n\n\n Molecular Genetics and Genomics, 299(1): 44. April 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"Genome-wide$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{billon_genome-wide_2024,\n\ttitle = {Genome-wide analysis identifies {MYH11} compound heterozygous variants leading to visceral myopathy corresponding to late-onset form of megacystis-microcolon-intestinal hypoperistalsis syndrome},\n\tvolume = {299},\n\tissn = {1617-4623},\n\turl = {https://doi.org/10.1007/s00438-024-02136-3},\n\tdoi = {10.1007/s00438-024-02136-3},\n\tabstract = {Megacystis-microcolon-hypoperistalsis-syndrome (MMIHS) is a rare and early-onset congenital disease characterized by massive abdominal distension due to a large non-obstructive bladder, a microcolon and decreased or absent intestinal peristalsis. While in most cases inheritance is autosomal dominant and associated with heterozygous variant in ACTG2 gene, an autosomal recessive transmission has also been described including pathogenic bialellic loss-of-function variants in MYH11. We report here a novel family with visceral myopathy related to MYH11 gene, confirmed by whole genome sequencing (WGS). WGS was performed in two siblings with unusual presentation of MMIHS and their two healthy parents. The 38 years-old brother had severe bladder dysfunction and intestinal obstruction, whereas the 30 years-old sister suffered from end-stage kidney disease with neurogenic bladder and recurrent sigmoid volvulus. WGS was completed by retrospective digestive pathological analyses. Compound heterozygous variants of MYH11 gene were identified, associating a deletion of 1.2 Mb encompassing MYH11 inherited from the father and an in-frame variant c.2578\\_2580del, p.Glu860del inherited from the mother. Pathology analyses of the colon and the rectum revealed structural changes which significance of which is discussed. Cardiac and vascular assessment of the mother was normal. This is the second report of a visceral myopathy corresponding to late-onset form of MMIHS related to compound heterozygosity in MYH11; with complete gene deletion and a hypomorphic allele in trans. The hypomorphic allele harbored by the mother raised the question of the risk of aortic disease in adults. This case shows the interest of WGS in deciphering complex phenotypes, allowing adapted diagnosis and genetic counselling.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2024-04-19},\n\tjournal = {Molecular Genetics and Genomics},\n\tauthor = {Billon, Clarisse and Piccoli, Giorgina Barbara and de Sainte Agathe, Jean-Madeleine and Stoeva, Radka and Derive, Nicolas and Heidet, Laurence and Berrebi, Dominique and Bruneval, Patrick and Jeunemaitre, Xavier and Hureaux, Marguerite},\n\tmonth = apr,\n\tyear = {2024},\n\tkeywords = {Alamut, Alamut v.2.10, Genome, Kidney failure, MYH11, Megacystis-microcolon, Vesicoureteral reflux},\n\tpages = {44},\n}\n\n

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\n \n\n \n \n \n \n \n \n Hong Kong Journal of Paediatrics [HK J Paediatr (New Series) 2024;29:97-99].\n \n \n \n \n\n\n \n Ma, J.; Chan, L.; and Cheung, H.\n\n\n \n\n\n\n April 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"Hong$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@misc{ma_hong_2024,\n\ttitle = {Hong {Kong} {Journal} of {Paediatrics} [{HK} {J} {Paediatr} ({New} {Series}) 2024;29:97-99]},\n\turl = {https://www.hkjpaed.org/details.asp?id=1486&show=1234},\n\tabstract = {A 7-month-old male infant presented with repeated vomiting and failure to thrive. Hypernatraemia, high serum osmolality, low urine osmolality, and lack of response to DDAVP, suggested diagnosis of nephrogenic diabetes insipidus. Genetic exome sequencing showed a novel hemizygous c.802\\_834dup, p.(Lys268\\_Val278dup) variant in exon 3 of AVPR2 gene, with in-frame duplication of 11 residues starting from 268th codon (NM\\_000054.6). This variant is of uncertain significance; the clinical phenotype was compatible with nephrogenic diabetes insipidus. Treatment with indomethacin, hydrochlorothiazide led to good clinical outcome.},\n\turldate = {2024-04-19},\n\tauthor = {Ma, JMY and Chan, LCN and Cheung, HM},\n\tmonth = apr,\n\tyear = {2024},\n\tkeywords = {AVPR2 mutation, CES v2, Congenital nephrogenic diabetes insipidus, NDI, clinical exome sequencing (CES)},\n}\n\n

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\n \n\n \n \n \n \n \n \n Beyond the phenotype: Exploring inherited retinal diseases with targeted next-generation sequencing in a Turkish cohort.\n \n \n \n \n\n\n \n Ozguc Caliskan, B.; Uslu, K.; Sinim Kahraman, N.; Erkilic, K.; Oner, A.; and Dundar, M.\n\n\n \n\n\n\n Clinical Genetics, n/a(n/a). April 2024.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/cge.14529\n\n\n\n
\n\n\n\n \n \n $\"Beyond$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{ozguc_caliskan_beyond_2024,\n\ttitle = {Beyond the phenotype: {Exploring} inherited retinal diseases with targeted next-generation sequencing in a {Turkish} cohort},\n\tvolume = {n/a},\n\tcopyright = {© 2024 The Authors. Clinical Genetics published by John Wiley \\& Sons Ltd.},\n\tissn = {1399-0004},\n\tshorttitle = {Beyond the phenotype},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1111/cge.14529},\n\tdoi = {10.1111/cge.14529},\n\tabstract = {This research aims to compile recent clinical and genetic data from Turkish patients with inherited retinal disorders and evaluate the effectiveness of targeted Next-generation sequencing panels. The study included Turkish individuals with hereditary retinal diseases who visited the Medical Genetic Department of Erciyes University between 2019 and 2022. One proband per family was selected based on eligibility. We used Hereditary Disorder Solution (HDS) by Sophia Genetics and performed next-generation sequencing (NGS) with Illumina NextSeq-500. Bioinformatics analysis using Sophia DDM® SaaS algorithms and ACMG guidelines classified genomic changes. The study involved 354 probands. Disease-causing variants were found in 58.1\\% of patients, with ABCA4, USH2A, RDH12, and EYS being the most frequently implicated genes. Forty-eight novel variants were detected. This study enhances the knowledge of clinical diagnoses, symptom onset, inheritance patterns, and genetic details for Turkish individuals with hereditary retinal disease. It contributes to broader health strategies by enabling comparisons with other studies.},\n\tlanguage = {en},\n\tnumber = {n/a},\n\turldate = {2024-04-11},\n\tjournal = {Clinical Genetics},\n\tauthor = {Ozguc Caliskan, Busra and Uslu, Kubra and Sinim Kahraman, Neslihan and Erkilic, Kuddusi and Oner, Ayse and Dundar, Munis},\n\tmonth = apr,\n\tyear = {2024},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/cge.14529},\n\tkeywords = {DDM, HDS, Hereditary Disorder Solution, genetic diagnosis, inherited retinal disease, retinitis pigmentosa, targeted next-generation sequencing, vision loss},\n}\n\n

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\n \n\n \n \n \n \n \n \n Establishment and molecular characterization of HCB-541, a novel and aggressive human cutaneous squamous cell carcinoma cell line.\n \n \n \n \n\n\n \n Laus, A. C.; Gomes, I. N. F.; da Silva, A. L. V.; da Silva, L. S.; Milan, M. B.; AparecidaTeixeira, S.; Martin, A. C. B. M.; do Nascimento Braga Pereira, L.; de Carvalho, C. E. B.; Crovador, C. S.; de Paula, F. E.; Nascimento, F. C.; de Freitas, H. T.; de Lima Vazquez, V.; Reis, R. M.; and da Silva-Oliveira, R. J.\n\n\n \n\n\n\n Human Cell. April 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"Establishment$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{laus_establishment_2024,\n\ttitle = {Establishment and molecular characterization of {HCB}-541, a novel and aggressive human cutaneous squamous cell carcinoma cell line},\n\tissn = {1749-0774},\n\turl = {https://doi.org/10.1007/s13577-024-01054-1},\n\tdoi = {10.1007/s13577-024-01054-1},\n\tabstract = {Cutaneous squamous cell carcinoma (cSCC) is a common type of skin cancer that can result in significant morbidity, although it is usually well-managed and rarely metastasizes. However, the lack of commercially available cSCC cell lines hinders our understanding of this disease. This study aims to establish and characterize a new metastatic cSCC cell line derived from a Brazilian patient. A tumor biopsy was taken from a metastatic cSCC patient, immortalized, and named HCB-541 after several passages. The cytokeratin expression profile, karyotypic alterations, mutational analysis, mRNA and protein differential expression, tumorigenic capacity in xenograft models, and drug sensitivity were analyzed. The HCB-541 cell line showed a doubling time between 20 and 30 h and high tumorigenic capacity in the xenograft mouse model. The HCB-541 cell line showed hypodiploid and hypotetraploidy populations. We found pathogenic mutations in TP53 p.(Arg248Leu), HRAS (Gln61His) and TERT promoter (C228T) and high-level microsatellite instability (MSI-H) in both tumor and cell line. We observed 37 cancer-related genes differentially expressed when compared with HACAT control cells. The HCB-541 cells exhibited high phosphorylated levels of EGFR, AXL, Tie, FGFR, and ROR2, and high sensitivity to cisplatin, carboplatin, and EGFR inhibitors. Our study successfully established HCB-541, a new cSCC cell line that could be useful as a valuable biological model for understanding the biology and therapy of metastatic skin cancer.},\n\tlanguage = {en},\n\turldate = {2024-04-11},\n\tjournal = {Human Cell},\n\tauthor = {Laus, Ana Carolina and Gomes, Izabela Natalia Faria and da Silva, Aline Larissa Virginio and da Silva, Luciane Sussuchi and Milan, Mirella Baroni and AparecidaTeixeira, Silvia and Martin, Ana Carolina Baptista Moreno and do Nascimento Braga Pereira, Letícia and de Carvalho, Carlos Eduardo Barbosa and Crovador, Camila Souza and de Paula, Flávia Escremin and Nascimento, Flávia Caroline and de Freitas, Helder Teixeira and de Lima Vazquez, Vinicius and Reis, Rui Manuel and da Silva-Oliveira, Renato José},\n\tmonth = apr,\n\tyear = {2024},\n\tkeywords = {Cell line establishment, Custom Cancer Panel, Cutaneous squamous cell carcinoma, DDM, In vivo model, MSI, MicroSatellite Instability analysis (MSI), Molecular profile, microsatellite instability},\n}\n\n

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\n \n\n \n \n \n \n \n \n Copy number signatures and CCNE1 amplification reveal the involvement of replication stress in high-grade endometrial tumors oncogenesis.\n \n \n \n \n\n\n \n Marlin, R.; Loger, J.; Joachim, C.; Ebring, C.; Robert-Siegwald, G.; Pennont, S.; Rose, M.; Raguette, K.; Suez-Panama, V.; Ulric-Gervaise, S.; Lusbec, S.; Bera, O.; Vallard, A.; Aline-Fardin, A.; Colomba, E.; and Jean-Laurent, M.\n\n\n \n\n\n\n Cellular Oncology. April 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"Copy$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{marlin_copy_2024,\n\ttitle = {Copy number signatures and {CCNE1} amplification reveal the involvement of replication stress in high-grade endometrial tumors oncogenesis},\n\tissn = {2211-3436},\n\turl = {https://doi.org/10.1007/s13402-024-00942-w},\n\tdoi = {10.1007/s13402-024-00942-w},\n\tabstract = {Managing high-grade endometrial cancer in Martinique poses significant challenges. The diversity of copy number alterations in high-grade endometrial tumors, often associated with a TP53 mutation, is a key factor complicating treatment. Due to the high incidence of high-grade tumors with poor prognosis, our study aimed to characterize the molecular signature of these tumors within a cohort of 25 high-grade endometrial cases.},\n\tlanguage = {en},\n\turldate = {2024-04-11},\n\tjournal = {Cellular Oncology},\n\tauthor = {Marlin, Regine and Loger, Jean-Samuel and Joachim, Clarisse and Ebring, Coralie and Robert-Siegwald, Guillaume and Pennont, Sabrina and Rose, Mickaelle and Raguette, Kevin and Suez-Panama, Valerie and Ulric-Gervaise, Sylviane and Lusbec, Sylvie and Bera, Odile and Vallard, Alexis and Aline-Fardin, Aude and Colomba, Emeline and Jean-Laurent, Mehdi},\n\tmonth = apr,\n\tyear = {2024},\n\tkeywords = {CCNE1 amplification, Copy number signature, DDM, HRD, High-grade endometrial cancer, Replication stress, homologous recombination deficiency},\n}\n\n

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\n \n\n \n \n \n \n \n \n Molecular Features of HHV8 Monoclonal Microlymphoma Associated with Kaposi Sarcoma and Multicentric Castleman Disease in an HIV-Negative Patient.\n \n \n \n \n\n\n \n Rogges, E.; Pelliccia, S.; Savio, C.; Lopez, G.; Della Starza, I.; La Verde, G.; and Di Napoli, A.\n\n\n \n\n\n\n International Journal of Molecular Sciences, 25(7): 3775. March 2024.\n Number: 7 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Molecular$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{rogges_molecular_2024,\n\ttitle = {Molecular {Features} of {HHV8} {Monoclonal} {Microlymphoma} {Associated} with {Kaposi} {Sarcoma} and {Multicentric} {Castleman} {Disease} in an {HIV}-{Negative} {Patient}},\n\tvolume = {25},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {1422-0067},\n\turl = {https://www.mdpi.com/1422-0067/25/7/3775},\n\tdoi = {10.3390/ijms25073775},\n\tabstract = {Human herpesvirus 8 (HHV8)-associated diseases include Kaposi sarcoma (KS), multicentric Castleman disease (MCD), germinotropic lymphoproliferative disorder (GLPD), Kaposi sarcoma inflammatory cytokine syndrome (KICS), HHV8-positive diffuse large B-cell lymphoma (HHV8+ DLBCL), primary effusion lymphoma (PEL), and extra-cavitary PEL (ECPEL). We report the case of a human immunodeficiency virus (HIV)-negative male treated for cutaneous KS, who developed generalized lymphadenopathy, hepatosplenomegaly, pleural and abdominal effusions, renal insufficiency, and pancytopenia. The excised lymph node showed features of concomitant involvement by micro-KS and MCD, with aggregates of HHV8+, Epstein Barr virus (EBV)-negative, IgM+, and lambda+ plasmablasts reminiscent of microlymphoma. Molecular investigations revealed a somatically hypermutated (SHM) monoclonal rearrangement of the immunoglobulin heavy chain (IGH), accounting for 4\\% of the B-cell population of the lymph node. Mutational analyses identified a pathogenic variant of KMT2D and variants of unknown significance in KMT2D, FOXO1, ARID1A, and KMT2A. The patient died shortly after surgery. The histological features (HHV8+, EBV−, IgM+, Lambda+, MCD+), integrated with the molecular findings (monoclonal IGH, SHM+, KMT2D mutated), supported the diagnosis of a monoclonal HHV8+ microlymphoma, with features intermediate between an incipient HHV8+ DLBCL and an EBV-negative ECPEL highlighting the challenges in the accurate classification of HHV8-driven lymphoid proliferations.},\n\tlanguage = {en},\n\tnumber = {7},\n\turldate = {2024-04-02},\n\tjournal = {International Journal of Molecular Sciences},\n\tauthor = {Rogges, Evelina and Pelliccia, Sabrina and Savio, Camilla and Lopez, Gianluca and Della Starza, Irene and La Verde, Giacinto and Di Napoli, Arianna},\n\tmonth = mar,\n\tyear = {2024},\n\tnote = {Number: 7\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {DDM, HHV8, HHV8+ DLBCL, Lymphoma solution, MCD, extra-cavitary PEL, microlymphoma, mutations, somatic hypermutation},\n\tpages = {3775},\n}\n\n

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\n \n\n \n \n \n \n \n \n Expanding the clinical spectrum of biglycan-related Meester-Loeys syndrome.\n \n \n \n \n\n\n \n Meester, J. A. N.; Hebert, A.; Bastiaansen, M.; Rabaut, L.; Bastianen, J.; Boeckx, N.; Ashcroft, K.; Atwal, P. S.; Benichou, A.; Billon, C.; Blankensteijn, J. D.; Brennan, P.; Bucks, S. A.; Campbell, I. M.; Conrad, S.; Curtis, S. L.; Dasouki, M.; Dent, C. L.; Eden, J.; Goel, H.; Hartill, V.; Houweling, A. C.; Isidor, B.; Jackson, N.; Koopman, P.; Korpioja, A.; Kraatari-Tiri, M.; Kuulavainen, L.; Lee, K.; Low, K. J.; Lu, A. C.; McManus, M. L.; Oakley, S. P.; Oliver, J.; Organ, N. M.; Overwater, E.; Revencu, N.; Trainer, A. H.; Trivedi, B.; Turner, C. L. S.; Whittington, R.; Zankl, A.; Zentner, D.; Van Laer, L.; Verstraeten, A.; and Loeys, B. L.\n\n\n \n\n\n\n npj Genomic Medicine, 9(1): 1–9. March 2024.\n Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"Expanding$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{meester_expanding_2024,\n\ttitle = {Expanding the clinical spectrum of biglycan-related {Meester}-{Loeys} syndrome},\n\tvolume = {9},\n\tcopyright = {2024 The Author(s)},\n\tissn = {2056-7944},\n\turl = {https://www.nature.com/articles/s41525-024-00413-z},\n\tdoi = {10.1038/s41525-024-00413-z},\n\tabstract = {Pathogenic loss-of-function variants in BGN, an X-linked gene encoding biglycan, are associated with Meester-Loeys syndrome (MRLS), a thoracic aortic aneurysm/dissection syndrome. Since the initial publication of five probands in 2017, we have considerably expanded our MRLS cohort to a total of 18 probands (16 males and 2 females). Segregation analyses identified 36 additional BGN variant-harboring family members (9 males and 27 females). The identified BGN variants were shown to lead to loss-of-function by cDNA and Western Blot analyses of skin fibroblasts or were strongly predicted to lead to loss-of-function based on the nature of the variant. No (likely) pathogenic missense variants without additional (predicted) splice effects were identified. Interestingly, a male proband with a deletion spanning the coding sequence of BGN and the 5’ untranslated region of the downstream gene (ATP2B3) presented with a more severe skeletal phenotype. This may possibly be explained by expressional activation of the downstream ATPase ATP2B3 (normally repressed in skin fibroblasts) driven by the remnant BGN promotor. This study highlights that aneurysms and dissections in MRLS extend beyond the thoracic aorta, affecting the entire arterial tree, and cardiovascular symptoms may coincide with non-specific connective tissue features. Furthermore, the clinical presentation is more severe and penetrant in males compared to females. Extensive analysis at RNA, cDNA, and/or protein level is recommended to prove a loss-of-function effect before determining the pathogenicity of identified BGN missense and non-canonical splice variants. In conclusion, distinct mechanisms may underlie the wide phenotypic spectrum of MRLS patients carrying loss-of-function variants in BGN.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2024-04-02},\n\tjournal = {npj Genomic Medicine},\n\tauthor = {Meester, Josephina A. N. and Hebert, Anne and Bastiaansen, Maaike and Rabaut, Laura and Bastianen, Jarl and Boeckx, Nele and Ashcroft, Kathryn and Atwal, Paldeep S. and Benichou, Antoine and Billon, Clarisse and Blankensteijn, Jan D. and Brennan, Paul and Bucks, Stephanie A. and Campbell, Ian M. and Conrad, Solène and Curtis, Stephanie L. and Dasouki, Majed and Dent, Carolyn L. and Eden, James and Goel, Himanshu and Hartill, Verity and Houweling, Arjan C. and Isidor, Bertrand and Jackson, Nicola and Koopman, Pieter and Korpioja, Anita and Kraatari-Tiri, Minna and Kuulavainen, Liina and Lee, Kelvin and Low, Karen J. and Lu, Alan C. and McManus, Morgan L. and Oakley, Stephen P. and Oliver, James and Organ, Nicole M. and Overwater, Eline and Revencu, Nicole and Trainer, Alison H. and Trivedi, Bhavya and Turner, Claire L. S. and Whittington, Rebecca and Zankl, Andreas and Zentner, Dominica and Van Laer, Lut and Verstraeten, Aline and Loeys, Bart L.},\n\tmonth = mar,\n\tyear = {2024},\n\tnote = {Publisher: Nature Publishing Group},\n\tkeywords = {Alamut, Alamut Visual Plus, Aneurysm, Disease genetics, Medical genomics, Mutation},\n\tpages = {1--9},\n}\n\n

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\n \n\n \n \n \n \n \n \n Novel Synonymous and Deep Intronic Variants Causing Primary and Secondary Pyruvate Dehydrogenase Complex Deficiency.\n \n \n \n \n\n\n \n Bruhn, H.; Naess, K.; Ygberg, S.; Peña-Pérez, L.; Lesko, N.; Wibom, R.; Freyer, C.; Stranneheim, H.; Wedell, A.; and Wredenberg, A.\n\n\n \n\n\n\n Human Mutation, 2024: e1611838. March 2024.\n Publisher: Hindawi\n\n\n\n
\n\n\n\n \n \n $\"Novel$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{bruhn_novel_2024,\n\ttitle = {Novel {Synonymous} and {Deep} {Intronic} {Variants} {Causing} {Primary} and {Secondary} {Pyruvate} {Dehydrogenase} {Complex} {Deficiency}},\n\tvolume = {2024},\n\tissn = {1059-7794},\n\turl = {https://www.hindawi.com/journals/humu/2024/1611838/},\n\tdoi = {10.1155/2024/1611838},\n\tabstract = {Pyruvate dehydrogenase complex deficiency (PDCD) is a defect of aerobic carbohydrate metabolism that causes neurological disorders with varying degrees of severity. We report the clinical, biochemical, and molecular findings in patients with primary and secondary PDCD caused by novel atypical genetic variants. Whole-genome sequencing (WGS) identified the synonymous variants c.447A{\\textgreater}G, p.(Lys149=) and c.570C{\\textgreater}T, p.(Cys190=) in pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1), the deep intronic variants c.1023+2267G{\\textgreater}A and c.1023+2302A{\\textgreater}G in pyruvate dehydrogenase complex component X (PDHX), and c.185+15054G{\\textgreater}A in thiamine pyrophosphokinase (TPK1). Analysis by Sanger and RNA sequencing of cDNA from patient blood and/or cultured fibroblasts showed that the synonymous variants in PDHA1 lead to aberrant splicing and skipping of exons 5 and 5-6 in one of the patients and transcripts lacking exon 6 in the other. The deep intronic variants in PDHX and TPK1 lead to insertion of intronic sequence in the corresponding transcripts. The splice defects in PDHA1 were more pronounced in cultured fibroblasts than in blood. Our findings expand the spectrum of pathogenic variants causing PDCD and highlight the importance of atypical variants leading to aberrant splicing. The severity of the splice defects and resulting biochemical dysfunction varied between tissues, stressing the importance of performing biochemical and transcript analysis in affected tissues. The two males with hemizygous synonymous PDHA1 variants have a mild phenotype and higher PDH enzyme activity than expected, which is consistent with aberrant but leaky splicing with a proportion of the transcripts remaining correctly spliced.},\n\tlanguage = {en},\n\turldate = {2024-04-02},\n\tjournal = {Human Mutation},\n\tauthor = {Bruhn, Helene and Naess, Karin and Ygberg, Sofia and Peña-Pérez, Lucía and Lesko, Nicole and Wibom, Rolf and Freyer, Christoph and Stranneheim, Henrik and Wedell, Anna and Wredenberg, Anna},\n\tmonth = mar,\n\tyear = {2024},\n\tnote = {Publisher: Hindawi},\n\tkeywords = {Alamut, Alamut Visual Plus, Neurodegenerative Diseases, Neurological Phenotype, PDCD},\n\tpages = {e1611838},\n}\n\n

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\n \n\n \n \n \n \n \n \n Bone marrow reinvestigation leading to the diagnosis of VEXAS syndrome.\n \n \n \n \n\n\n \n Strasser, B.; Kranewitter, W.; Hofer, H.; and Haushofer, A.\n\n\n \n\n\n\n Laboratory Medicine,lmae020. March 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"Bone$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{strasser_bone_2024,\n\ttitle = {Bone marrow reinvestigation leading to the diagnosis of {VEXAS} syndrome},\n\tissn = {0007-5027},\n\turl = {https://doi.org/10.1093/labmed/lmae020},\n\tdoi = {10.1093/labmed/lmae020},\n\tabstract = {A 46-year-old male patient presented with inflammatory diseases over more than 3 years. The patient suffered from recurrent pleuritis, polychondritis, orbital phlegmon, fever, and skin lesions. A bone marrow puncture added myelodysplastic syndrome to the patient’s history. A focused cytomorphological reinvestigation of the archived bone marrow aspirate smears detected significant vacuolization of erythroid and myeloid precursor cells. Target sequencing revealed the UBA1 (p.Met41Thr) hotspot mutation that established the diagnosis of VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome.},\n\turldate = {2024-04-02},\n\tjournal = {Laboratory Medicine},\n\tauthor = {Strasser, Bernhard and Kranewitter, Wolfgang and Hofer, Harald and Haushofer, Alexander},\n\tmonth = mar,\n\tyear = {2024},\n\tkeywords = {Custom, Custom Cancer Panel, Custom MYS, Myeloid},\n\tpages = {lmae020},\n}\n\n

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\n \n\n \n \n \n \n \n \n Genomic analysis in Chilean patients with suspected Rett syndrome: keep a broad differential diagnosis.\n \n \n \n \n\n\n \n Brito, F.; Lagos, C.; Cubillos, J.; Orellana, J.; Gajardo, M.; Böhme, D.; Encina, G.; and Repetto, G.\n\n\n \n\n\n\n . March 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"Genomic$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{brito_genomic_2024,\n\ttitle = {Genomic analysis in {Chilean} patients with suspected {Rett} syndrome: keep a broad differential diagnosis},\n\tshorttitle = {Genomic analysis in {Chilean} patients with suspected {Rett} syndrome},\n\turl = {https://hdl.handle.net/11447/8558},\n\tabstract = {Introduction: Rett syndrome (RTT, MIM \\#312750) is a rare genetic disorder that leads to developmental regression and severe disability and is caused by pathogenic variants in the MECP2 gene. The diagnosis of RTT is based on clinical features and, depending on resources and access, on molecular confirmation. There is scarce information on molecular diagnosis from patients in Latin America, mostly due to limited availability and coverage of genomic testing. This pilot study aimed to implement genomic testing and characterize clinical and molecular findings in a group of Chilean patients with a clinical diagnosis of RTT. Methods: Twenty-eight patients with suspected RTT underwent characterization of phenotypic manifestations and molecular testing using Clinical Exome SolutionTM CES\\_V2 by SOPHiA Genetics. Data was analyzed using the commercial bioinformatics platform, SOPHiA DDMTM. A virtual panel of 34 genes, including MECP2 and other genes that are in the differential diagnosis of RTT, was used to prioritize initial analyses, followed by evaluation of the complete exome sequence data. Results: Twelve patients (42.8\\% of participants) had variants in MECP2, of which 11 (39.2\\%) were interpreted as pathogenic/likely pathogenic (P/LP), thus confirming the diagnosis of RTT in them. Eight additional patients (28.5\\%) harbored ten variants in nine other genes. Four of these variants were interpreted as P/LP (14.2\\%) (GRIN2B, MADD, TRPM3 and ZEB2) resulting in alternative neurodevelopmental diagnoses, and six were considered of uncertain significance. No evident candidate variant was found for eight patients. Discussion: This study allowed to reach a diagnosis in half of the participants. The diagnosis of RTT was confirmed in over a third of them, while others were found to have alternative neurodevelopmental disorders. Further evaluation is needed to identify the cause in those with negative or uncertain results. This information is useful for the patients, families, and clinicians to guide clinical management,},\n\tlanguage = {en},\n\turldate = {2024-03-25},\n\tauthor = {Brito, Florencia and Lagos, Catalina and Cubillos, Jessica and Orellana, Joan and Gajardo, Mallen and Böhme, Daniela and Encina, Gonzalo and Repetto, Gabriela},\n\tmonth = mar,\n\tyear = {2024},\n\tkeywords = {CES v2, Clinical Exome Solution, DDM, Gene panel, Genomics, MeCP2, Neurodevelopmental disorders, Rett syndrome},\n}\n\n

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\n Introduction: Rett syndrome (RTT, MIM #312750) is a rare genetic disorder that leads to developmental regression and severe disability and is caused by pathogenic variants in the MECP2 gene. The diagnosis of RTT is based on clinical features and, depending on resources and access, on molecular confirmation. There is scarce information on molecular diagnosis from patients in Latin America, mostly due to limited availability and coverage of genomic testing. This pilot study aimed to implement genomic testing and characterize clinical and molecular findings in a group of Chilean patients with a clinical diagnosis of RTT. Methods: Twenty-eight patients with suspected RTT underwent characterization of phenotypic manifestations and molecular testing using Clinical Exome SolutionTM CES_V2 by SOPHiA Genetics. Data was analyzed using the commercial bioinformatics platform, SOPHiA DDMTM. A virtual panel of 34 genes, including MECP2 and other genes that are in the differential diagnosis of RTT, was used to prioritize initial analyses, followed by evaluation of the complete exome sequence data. Results: Twelve patients (42.8% of participants) had variants in MECP2, of which 11 (39.2%) were interpreted as pathogenic/likely pathogenic (P/LP), thus confirming the diagnosis of RTT in them. Eight additional patients (28.5%) harbored ten variants in nine other genes. Four of these variants were interpreted as P/LP (14.2%) (GRIN2B, MADD, TRPM3 and ZEB2) resulting in alternative neurodevelopmental diagnoses, and six were considered of uncertain significance. No evident candidate variant was found for eight patients. Discussion: This study allowed to reach a diagnosis in half of the participants. The diagnosis of RTT was confirmed in over a third of them, while others were found to have alternative neurodevelopmental disorders. Further evaluation is needed to identify the cause in those with negative or uncertain results. This information is useful for the patients, families, and clinicians to guide clinical management,\n

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\n \n\n \n \n \n \n \n \n Towards Uncovering the Role of Incomplete Penetrance in Maculopathies through Sequencing of 105 Disease-Associated Genes.\n \n \n \n \n\n\n \n Hitti-Malin, R. J.; Panneman, D. M.; Corradi, Z.; Boonen, E. G. M.; Astuti, G.; Dhaenens, C.; Stöhr, H.; Weber, B. H. F.; Sharon, D.; Banin, E.; Karali, M.; Banfi, S.; Ben-Yosef, T.; Glavač, D.; Farrar, G. J.; Ayuso, C.; Liskova, P.; Dudakova, L.; Vajter, M.; Ołdak, M.; Szaflik, J. P.; Matynia, A.; Gorin, M. B.; Kämpjärvi, K.; Bauwens, M.; De Baere, E.; Hoyng, C. B.; Li, C. H. Z.; Klaver, C. C. W.; Inglehearn, C. F.; Fujinami, K.; Rivolta, C.; Allikmets, R.; Zernant, J.; Lee, W.; Podhajcer, O. L.; Fakin, A.; Sajovic, J.; AlTalbishi, A.; Valeina, S.; Taurina, G.; Vincent, A. L.; Roberts, L.; Ramesar, R.; Sartor, G.; Luppi, E.; Downes, S. M.; van den Born, L. I.; McLaren, T. L.; De Roach, J. N.; Lamey, T. M.; Thompson, J. A.; Chen, F. K.; Tracewska, A. M.; Kamakari, S.; Sallum, J. M. F.; Bolz, H. J.; Kayserili, H.; Roosing, S.; and Cremers, F. P. M.\n\n\n \n\n\n\n Biomolecules, 14(3): 367. March 2024.\n Number: 3 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Towards$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{hitti-malin_towards_2024,\n\ttitle = {Towards {Uncovering} the {Role} of {Incomplete} {Penetrance} in {Maculopathies} through {Sequencing} of 105 {Disease}-{Associated} {Genes}},\n\tvolume = {14},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2218-273X},\n\turl = {https://www.mdpi.com/2218-273X/14/3/367},\n\tdoi = {10.3390/biom14030367},\n\tabstract = {Inherited macular dystrophies (iMDs) are a group of genetic disorders, which affect the central region of the retina. To investigate the genetic basis of iMDs, we used single-molecule Molecular Inversion Probes to sequence 105 maculopathy-associated genes in 1352 patients diagnosed with iMDs. Within this cohort, 39.8\\% of patients were considered genetically explained by 460 different variants in 49 distinct genes of which 73 were novel variants, with some affecting splicing. The top five most frequent causative genes were ABCA4 (37.2\\%), PRPH2 (6.7\\%), CDHR1 (6.1\\%), PROM1 (4.3\\%) and RP1L1 (3.1\\%). Interestingly, variants with incomplete penetrance were revealed in almost one-third of patients considered solved (28.1\\%), and therefore, a proportion of patients may not be explained solely by the variants reported. This includes eight previously reported variants with incomplete penetrance in addition to CDHR1:c.783G{\\textgreater}A and CNGB3:c.1208G{\\textgreater}A. Notably, segregation analysis was not routinely performed for variant phasing—a limitation, which may also impact the overall diagnostic yield. The relatively high proportion of probands without any putative causal variant (60.2\\%) highlights the need to explore variants with incomplete penetrance, the potential modifiers of disease and the genetic overlap between iMDs and age-related macular degeneration. Our results provide valuable insights into the genetic landscape of iMDs and warrant future exploration to determine the involvement of other maculopathy genes.},\n\tlanguage = {en},\n\tnumber = {3},\n\turldate = {2024-03-25},\n\tjournal = {Biomolecules},\n\tauthor = {Hitti-Malin, Rebekkah J. and Panneman, Daan M. and Corradi, Zelia and Boonen, Erica G. M. and Astuti, Galuh and Dhaenens, Claire-Marie and Stöhr, Heidi and Weber, Bernhard H. F. and Sharon, Dror and Banin, Eyal and Karali, Marianthi and Banfi, Sandro and Ben-Yosef, Tamar and Glavač, Damjan and Farrar, G. Jane and Ayuso, Carmen and Liskova, Petra and Dudakova, Lubica and Vajter, Marie and Ołdak, Monika and Szaflik, Jacek P. and Matynia, Anna and Gorin, Michael B. and Kämpjärvi, Kati and Bauwens, Miriam and De Baere, Elfride and Hoyng, Carel B. and Li, Catherina H. Z. and Klaver, Caroline C. W. and Inglehearn, Chris F. and Fujinami, Kaoru and Rivolta, Carlo and Allikmets, Rando and Zernant, Jana and Lee, Winston and Podhajcer, Osvaldo L. and Fakin, Ana and Sajovic, Jana and AlTalbishi, Alaa and Valeina, Sandra and Taurina, Gita and Vincent, Andrea L. and Roberts, Lisa and Ramesar, Raj and Sartor, Giovanna and Luppi, Elena and Downes, Susan M. and van den Born, L. Ingeborgh and McLaren, Terri L. and De Roach, John N. and Lamey, Tina M. and Thompson, Jennifer A. and Chen, Fred K. and Tracewska, Anna M. and Kamakari, Smaragda and Sallum, Juliana Maria Ferraz and Bolz, Hanno J. and Kayserili, Hülya and Roosing, Susanne and Cremers, Frans P. M.},\n\tmonth = mar,\n\tyear = {2024},\n\tnote = {Number: 3\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Alamut Visual Plus, inherited, macula, maculopathies, penetrance, retinal, sequencing},\n\tpages = {367},\n}\n\n

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\n \n\n \n \n \n \n \n \n Clinical Utility of Genetic Testing with Geographical Locations in ADPKD: Describing New Variants.\n \n \n \n \n\n\n \n García Rabaneda, C.; Bellido Díaz, M. L.; Morales García, A. I.; Poyatos Andújar, A. M.; Bravo Soto, J.; Dayaldasani Khialani, A.; Martínez Atienza, M.; and Esteban de la Rosa, R. J.\n\n\n \n\n\n\n Journal of Clinical Medicine, 13(6): 1751. March 2024.\n Number: 6 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Clinical$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{garcia_rabaneda_clinical_2024,\n\ttitle = {Clinical {Utility} of {Genetic} {Testing} with {Geographical} {Locations} in {ADPKD}: {Describing} {New} {Variants}},\n\tvolume = {13},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2077-0383},\n\tshorttitle = {Clinical {Utility} of {Genetic} {Testing} with {Geographical} {Locations} in {ADPKD}},\n\turl = {https://www.mdpi.com/2077-0383/13/6/1751},\n\tdoi = {10.3390/jcm13061751},\n\tabstract = {Background: Our study aims to comment on all ADPKD variants identified in our health area and explain how they are distributed geographically, to identify new variants, and relate the more frequent variants with their renal phenotype in terms of kidney survival. Materials and Methods: We identified patients suffering from ADPKD in a specialized consultation unit; genealogical trees were constructed from the proband. According to the ultrasound-defined modified Ravine–Pei criteria, relatives classified as at risk were offered participation in the genetic study. Socio-demographic, clinical, and genetic factors related to the impact of the variant on the survival of the kidney and the patient, such as age at RRT beginning and age of death, were recorded. Results: In 37 families, 33 new variants of the PKD1 gene were identified, which probably produce a truncated protein. These variants included 2 large deletions, 19 frameshifts, and 12 stop-codons, all of which had not been previously described in the databases. In 10 families, six new probably pathogenic variants in the PKD2 gene were identified. These included three substitutions; two deletions, one of which was intronic and not associated with any family; and one duplication. A total of 11 missense variants in the PKD1 gene were grouped in 14 families and classified as probably pathogenic. We found that 33 VUS were grouped into 18 families and were not described in the databases, while another 15 were without grouping, and there was only 1 in the PKD2 gene. Some of these variants were present in patients with a different pathogenic variant (described or not), and the variant was probably benign. Renal survival curves were compared to nonsense versus missense variants on the PKD1 gene to check if there were any differences. A group of 328 patients with a nonsense variant was compared with a group of 264 with a missense variant; mean renal survival for truncated variants was lower (53.1 ± 0.46 years versus non-truncated variant 59.1 ± 1.36 years; Log Rank, Breslow, and Tarone Ware, p {\\textless} 0.05). Conclusions: To learn more about ADPKD, it is necessary to understand genetics. By describing new genetic variants, we are approaching creation of an accurate genetic map of the disease in our country, which could have prognostic and therapeutic implications in the future.},\n\tlanguage = {en},\n\tnumber = {6},\n\turldate = {2024-03-25},\n\tjournal = {Journal of Clinical Medicine},\n\tauthor = {García Rabaneda, Carmen and Bellido Díaz, María Luz and Morales García, Ana Isabel and Poyatos Andújar, Antonio Miguel and Bravo Soto, Juan and Dayaldasani Khialani, Anita and Martínez Atienza, Margarita and Esteban de la Rosa, Rafael Jose},\n\tmonth = mar,\n\tyear = {2024},\n\tnote = {Number: 6\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {ADPKD, DDM, Nephropathies Solution, geographical location, new variants},\n\tpages = {1751},\n}\n\n

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\n Background: Our study aims to comment on all ADPKD variants identified in our health area and explain how they are distributed geographically, to identify new variants, and relate the more frequent variants with their renal phenotype in terms of kidney survival. Materials and Methods: We identified patients suffering from ADPKD in a specialized consultation unit; genealogical trees were constructed from the proband. According to the ultrasound-defined modified Ravine–Pei criteria, relatives classified as at risk were offered participation in the genetic study. Socio-demographic, clinical, and genetic factors related to the impact of the variant on the survival of the kidney and the patient, such as age at RRT beginning and age of death, were recorded. Results: In 37 families, 33 new variants of the PKD1 gene were identified, which probably produce a truncated protein. These variants included 2 large deletions, 19 frameshifts, and 12 stop-codons, all of which had not been previously described in the databases. In 10 families, six new probably pathogenic variants in the PKD2 gene were identified. These included three substitutions; two deletions, one of which was intronic and not associated with any family; and one duplication. A total of 11 missense variants in the PKD1 gene were grouped in 14 families and classified as probably pathogenic. We found that 33 VUS were grouped into 18 families and were not described in the databases, while another 15 were without grouping, and there was only 1 in the PKD2 gene. Some of these variants were present in patients with a different pathogenic variant (described or not), and the variant was probably benign. Renal survival curves were compared to nonsense versus missense variants on the PKD1 gene to check if there were any differences. A group of 328 patients with a nonsense variant was compared with a group of 264 with a missense variant; mean renal survival for truncated variants was lower (53.1 ± 0.46 years versus non-truncated variant 59.1 ± 1.36 years; Log Rank, Breslow, and Tarone Ware, p \\textless 0.05). Conclusions: To learn more about ADPKD, it is necessary to understand genetics. By describing new genetic variants, we are approaching creation of an accurate genetic map of the disease in our country, which could have prognostic and therapeutic implications in the future.\n

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\n \n\n \n \n \n \n \n \n Diagnostic yield from cardiac gene testing for inherited cardiac conditions and re-evaluation of pre-ACMG variants of uncertain significance.\n \n \n \n \n\n\n \n Murphy, J.; Kirk, C. W.; Lambert, D. M.; McGorrian, C.; Walsh, R.; McVeigh, T. P.; Prendiville, T.; Ward, D.; Galvin, J.; and Lynch, S. A.\n\n\n \n\n\n\n Irish Journal of Medical Science (1971 -). March 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"Diagnostic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{murphy_diagnostic_2024,\n\ttitle = {Diagnostic yield from cardiac gene testing for inherited cardiac conditions and re-evaluation of pre-{ACMG} variants of uncertain significance},\n\tissn = {1863-4362},\n\turl = {https://doi.org/10.1007/s11845-024-03650-4},\n\tdoi = {10.1007/s11845-024-03650-4},\n\tabstract = {Inherited cardiomyopathies (HCM, DCM, ACM) and cardiac ion channelopathies (long QT/Brugada syndromes, CPVT) are associated with significant morbidity and mortality; however, diagnosis of a familial pathogenic variant in a proband allows for subsequent cascade screening of their at-risk relatives.},\n\tlanguage = {en},\n\turldate = {2024-03-18},\n\tjournal = {Irish Journal of Medical Science (1971 -)},\n\tauthor = {Murphy, Jane and Kirk, Claire W. and Lambert, Deborah M. and McGorrian, Catherine and Walsh, Roddy and McVeigh, Terri P. and Prendiville, Terence and Ward, Deirdre and Galvin, Joseph and Lynch, Sally Ann},\n\tmonth = mar,\n\tyear = {2024},\n\tkeywords = {Alamut, Alamut Visual Plus, Diagnostic yield, Hypertrophic cardiomyopathy, Inherited cardiac conditions, Long QT syndrome, Molecular autopsy, Sudden cardiac death},\n}\n\n

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\n \n\n \n \n \n \n \n \n Integrated diagnosis of grade 3-4 gliomas using targeted next-generation sequencing and traditional diagnostic data, and its overall implications on patient management.\n \n \n \n \n\n\n \n Kanan, D.; Safi, S.; Kanan, T.; Celik, S.; Oven, B. B.; and Yapicier, O.\n\n\n \n\n\n\n Brain Disorders,100126. March 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"Integrated$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{kanan_integrated_2024,\n\ttitle = {Integrated diagnosis of grade 3-4 gliomas using targeted next-generation sequencing and traditional diagnostic data, and its overall implications on patient management},\n\tissn = {2666-4593},\n\turl = {https://www.sciencedirect.com/science/article/pii/S2666459324000118},\n\tdoi = {10.1016/j.dscb.2024.100126},\n\tabstract = {Adult gliomas vary significantly in terms of their genetics, epigenetics, phenotypes as well as clinical outcomes1. Optimal tumor classification that leads to more precise diagnoses, and which influences therapy selection is hence critically important. Targeted next-generation sequencing (NGS) is a highly reliable and efficient novel tool for the identification of biomarkers for the diagnosis of CNS tumors2. In this study, we aimed to determine the implications of integrating NGS findings with the traditional diagnostic data on clinical diagnostics and patient management. All patients who were diagnosed with glioma at our institution between 2019-2020 and whose tumor biopsy materials were analyzed by both traditional histomorphological and immunohistochemical diagnostic techniques as well as NGS were included in our study. Patients’ information was retrieved from the electronic medical record. Data analyzed included the histopathologic diagnosis, tumor grade, ki67, and the mutation status of TP53 and /or IDH, as well as other genes such as BRAF and HER2 for some patients. The overall concordance between NGS and the traditional diagnostic tools for IDH and TP53 mutations was also evaluated. Further, we derived the overall survival of patients using the Kaplan-Meier estimate. We identified 9 patients with grade 3-4 gliomas whose biopsy materials were analyzed by NGS as well as traditional diagnostic tools. Our patients were 33.3\\% females and had a median age of 43 years old at diagnosis. In terms of the identification of gene mutations by NGS in comparison to immunohistochemistry (IHC), it was found that the concordance for mutant identification was 77.8\\% (7/9) for IDH mutations and 55.6\\% (5/9) for TP53 mutations. NGS further led to a change in patient management in which evidence-based targeted therapy (dabrafenib plus trametinib) was used for one patient (11.1\\%) with BRAF V600E mutated astroblastoma. Integrating NGS with traditional diagnostic tools for the diagnosis of gliomas can have significant implications on patients. Such integrated diagnosis can lead to more precise diagnosis, enhanced identification of molecular markers, and offers the potential of using targeted therapies for patients.},\n\turldate = {2024-03-18},\n\tjournal = {Brain Disorders},\n\tauthor = {Kanan, Duaa and Safi, Sebnem and Kanan, Tarek and Celik, Serkan and Oven, Bala Basak and Yapicier, Ozlem},\n\tmonth = mar,\n\tyear = {2024},\n\tkeywords = {NGS, STS, Solid Tumor Solution, brain tumors, glioma, targeted},\n\tpages = {100126},\n}\n\n

\n\n\n

\n Adult gliomas vary significantly in terms of their genetics, epigenetics, phenotypes as well as clinical outcomes1. Optimal tumor classification that leads to more precise diagnoses, and which influences therapy selection is hence critically important. Targeted next-generation sequencing (NGS) is a highly reliable and efficient novel tool for the identification of biomarkers for the diagnosis of CNS tumors2. In this study, we aimed to determine the implications of integrating NGS findings with the traditional diagnostic data on clinical diagnostics and patient management. All patients who were diagnosed with glioma at our institution between 2019-2020 and whose tumor biopsy materials were analyzed by both traditional histomorphological and immunohistochemical diagnostic techniques as well as NGS were included in our study. Patients’ information was retrieved from the electronic medical record. Data analyzed included the histopathologic diagnosis, tumor grade, ki67, and the mutation status of TP53 and /or IDH, as well as other genes such as BRAF and HER2 for some patients. The overall concordance between NGS and the traditional diagnostic tools for IDH and TP53 mutations was also evaluated. Further, we derived the overall survival of patients using the Kaplan-Meier estimate. We identified 9 patients with grade 3-4 gliomas whose biopsy materials were analyzed by NGS as well as traditional diagnostic tools. Our patients were 33.3% females and had a median age of 43 years old at diagnosis. In terms of the identification of gene mutations by NGS in comparison to immunohistochemistry (IHC), it was found that the concordance for mutant identification was 77.8% (7/9) for IDH mutations and 55.6% (5/9) for TP53 mutations. NGS further led to a change in patient management in which evidence-based targeted therapy (dabrafenib plus trametinib) was used for one patient (11.1%) with BRAF V600E mutated astroblastoma. Integrating NGS with traditional diagnostic tools for the diagnosis of gliomas can have significant implications on patients. Such integrated diagnosis can lead to more precise diagnosis, enhanced identification of molecular markers, and offers the potential of using targeted therapies for patients.\n

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\n \n\n \n \n \n \n \n \n Pleomorphic/solid lobular carcinoma of male breast with PALB2 germline mutation: case report and literature review.\n \n \n \n \n\n\n \n Rogges, E.; Corati, T.; Amato, M.; Campagna, D.; Farro, J.; Toffol, s. D.; Fortunato, L.; and Costarelli, L.\n\n\n \n\n\n\n Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology, 116: 62–68. March 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"Pleomorphic/solid$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{rogges_pleomorphicsolid_2024,\n\ttitle = {Pleomorphic/solid lobular carcinoma of male breast with {PALB2} germline mutation: case report and literature review},\n\tvolume = {116},\n\tcopyright = {Copyright (c) 2024 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology},\n\tissn = {1591-951X},\n\tshorttitle = {Pleomorphic/solid lobular carcinoma of male breast with {PALB2} germline mutation},\n\turl = {https://www.pathologica.it/article/view/936},\n\tdoi = {10.32074/1591-951X-936},\n\tabstract = {Male breast cancer (MBC) accounts for approximately 1\\% of all breast cancers and among these infiltrating lobular carcinomas (ILC) represents only 1-2\\% of all MBC cases. Pleomorphic invasive lobular carcinoma (PILC) is an aggressive variant of ILC with only eight cases reported until now in males. Up to 10\\% of MBC cases have a germline pathogenic variant in a predisposing gene such as BRCA1 and BRCA2 genes. Mutations in PALB2 (partner and localizer of BRCA2) have been reported in men with breast cancer, with a frequency that ranges from 0.8 to 6.4\\%, but it has never been reported in male ILC. Here, we report a rare and interesting case of an invasive pleomorphic/solid lobular carcinoma, which carries a pathogenic variant in PALB2 gene, and a family history of breast cancer without other well defined risk factors for developing this type of neoplasia. In addition, we review the current literature.\nRead the full article},\n\tlanguage = {en},\n\turldate = {2024-03-12},\n\tjournal = {Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology},\n\tauthor = {Rogges, Evelina and Corati, Tiberio and Amato, Michela and Campagna, Domenico and Farro, Juliette and Toffol, simona De and Fortunato, Lucio and Costarelli, Leopoldo},\n\tmonth = mar,\n\tyear = {2024},\n\tkeywords = {HCS, Hereditary Breast Cancer, Hereditary Cancer Solution, PALB2, germline mutations, lobular carcinoma (LC), male breast cancer (MBC)},\n\tpages = {62--68},\n}\n\n

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\n \n\n \n \n \n \n \n \n Complex analysis of the national Hereditary angioedema cohort in Slovakia – Identification of 12 novel variants in SERPING1 gene.\n \n \n \n \n\n\n \n Markocsy, A.; Hrubiskova, K.; Hrubisko, M.; Freiberger, T.; Grombirikova, H.; Dolesova, L.; Slivka Vavrova, L.; Lohajova Behulova, R.; Ondrusova, M.; Banovcin, P.; Vorcakova, K.; and Jesenak, M.\n\n\n \n\n\n\n World Allergy Organization Journal, 17(3): 100885. March 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"Complex$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{markocsy_complex_2024,\n\ttitle = {Complex analysis of the national {Hereditary} angioedema cohort in {Slovakia} – {Identification} of 12 novel variants in \\textit{{SERPING1}} gene},\n\tvolume = {17},\n\tissn = {1939-4551},\n\turl = {https://www.sciencedirect.com/science/article/pii/S1939455124000164},\n\tdoi = {10.1016/j.waojou.2024.100885},\n\tabstract = {Background\nHereditary angioedema (HAE) is a rare autosomal dominant genetic disease characterised by acute episodes of non-pruritic skin and submucosal swelling caused by increase in vascular permeability.\nObjective\nHere we present the first complex analysis of the National HAE Slovakian cohort with the detection of 12 previously un-published genetic variants in SERPING1 gene.\nMethods\nIn patients diagnosed with hereditary angioedema caused by deficiency or dysfunction of C1 inhibitor (C1–INH-HAE) based on clinical manifestation and complement measurements, SERPING1 gene was tested by DNA sequencing (Sanger sequencing/massive parallel sequencing) and/or multiplex ligation-dependent probe amplification for detection of large rearrangements.\nResults\nThe Slovakian national cohort consisted of 132 living patients with confirmed HAE. We identified 51 index cases (32 families, 19 sporadic patients/112 adults, 20 children). One hundred seventeen patients had HAE caused by deficiency of C1 inhibitor (C1–INH-HAE-1) and 15 patients had HAE caused by dysfunction of C1 inhibitor (C1–INH-HAE-2). The prevalence of HAE in Slovakia has recently been calculated to 1:41 280 which is higher than average calculated prevalence. The estimated incidence was 1:1360 000. Molecular-genetic testing of the SERPING1 gene found 22 unique causal variants in 26 index cases, including 12 previously undescribed and unreported.\nConclusion\nThe first complex report about epidemiology and genetics of the Slovakian national HAE cohort expands the knowledge of the C1–INH-HAE genetics. Twelve novel causal variants were present in the half of the index cases. A higher percentage of inframe variants comparing to other studies was observed. Heterozygous deletion of exon 3 found in a large C1–INH-HAE-1 family probably causes the dysregulation of the splicing isoforms balance and leads to the decrease of full-length C1–INH level.},\n\tnumber = {3},\n\turldate = {2024-03-12},\n\tjournal = {World Allergy Organization Journal},\n\tauthor = {Markocsy, Adam and Hrubiskova, Katarina and Hrubisko, Martin and Freiberger, Tomas and Grombirikova, Hana and Dolesova, Lenka and Slivka Vavrova, Ludmila and Lohajova Behulova, Regina and Ondrusova, Martina and Banovcin, Peter and Vorcakova, Karolina and Jesenak, Milos},\n\tmonth = mar,\n\tyear = {2024},\n\tkeywords = {Angioedemas, CES, Clinical Exome Solution, Complement C1 inhibitor protein, DDM, Genetic testing, Hereditary/epidemiology, Hereditary/genetics, Slovakia, clinical exome sequencing, clinical exome sequencing (CES)},\n\tpages = {100885},\n}\n\n

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\n \n\n \n \n \n \n \n \n Magnetic resonance imaging based kidney volume assessment for risk stratification in pediatric autosomal dominant polycystic kidney disease.\n \n \n \n \n\n\n \n Yilmaz, K.; Saygili, S.; Canpolat, N.; Akgun-Dogan, O.; Yuruk Yildirim, Z. N.; Cicek-Oksuz, R. Y.; Oner, H. A.; Aksu, B.; Akyel, N. G.; Oguzhan-Hamis, O.; Dursun, H.; Yavuz, S.; Cicek, N.; Akinci, N.; Karabag Yilmaz, E.; Agbas, A.; Nayir, A. N.; Konukoglu, D.; Kurugoglu, S.; Sever, L.; and Caliskan, S.\n\n\n \n\n\n\n Frontiers in Pediatrics, 12. February 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"Magnetic$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{yilmaz_magnetic_2024,\n\ttitle = {Magnetic resonance imaging based kidney volume assessment for risk stratification in pediatric autosomal dominant polycystic kidney disease},\n\tvolume = {12},\n\tissn = {2296-2360},\n\turl = {https://www.frontiersin.org/articles/10.3389/fped.2024.1357365},\n\tabstract = {IntroductionIn the pediatric context, most children with autosomal dominant polycystic kidney disease (ADPKD) maintain a normal glomerular filtration rate (GFR) despite underlying structural kidney damage, highlighting the critical need for early intervention and predictive markers. Due to the inverse relationship between kidney volume and kidney function, risk assessments have been presented on the basis of kidney volume. The aim of this study was to use magnetic resonance imaging (MRI)-based kidney volume assessment for risk stratification in pediatric ADPKD and to investigate clinical and genetic differences among risk groups.MethodsThis multicenter, cross-sectional, and case-control study included 75 genetically confirmed pediatric ADPKD patients (5–18 years) and 27 controls. Kidney function was assessed by eGFR calculated from serum creatinine and cystatin C using the CKiD-U25 equation. Blood pressure was assessed by both office and 24-hour ambulatory measurements. Kidney volume was calculated from MRI using the stereological method. Total kidney volume was adjusted for the height (htTKV). Patients were stratified from A to E classes according to the Leuven Imaging Classification (LIC) using MRI-derived htTKV.ResultsMedian (Q1-Q3) age of the patients was 6.0 (2.0–10.0) years, 56\\% were male. There were no differences in sex, age, height-SDS, or GFR between the patient and control groups. Of the patients, 89\\% had PKD1 and 11\\% had PKD2 mutations. Non-missense mutations were 73\\% in PKD1 and 75\\% in PKD2. Twenty patients (27\\%) had hypertension based on ABPM. Median htTKV of the patients was significantly higher than controls (141 vs. 117 ml/m, p = 0.0003). LIC stratification revealed Classes A (38.7\\%), B (28\\%), C (24\\%), and D + E (9.3\\%). All children in class D + E and 94\\% in class C had PKD1 variants. Class D + E patients had significantly higher blood pressure values and hypertension compared to other classes (p {\\textgreater} 0.05 for all).DiscussionThis study distinguishes itself by using MRI-based measurements of kidney volume to stratify pediatric ADPKD patients into specific risk groups. It is important to note that PKD1 mutation and elevated blood pressure were higher in the high-risk groups stratified by age and kidney volume. Our results need to be confirmed in further studies.},\n\turldate = {2024-02-29},\n\tjournal = {Frontiers in Pediatrics},\n\tauthor = {Yilmaz, Kubra and Saygili, Seha and Canpolat, Nur and Akgun-Dogan, Ozlem and Yuruk Yildirim, Zeynep Nagehan and Cicek-Oksuz, Rumeysa Yasemin and Oner, Huseyin Adil and Aksu, Bagdagul and Akyel, Nazli Gulsum and Oguzhan-Hamis, Ozge and Dursun, Hasan and Yavuz, Sevgi and Cicek, Neslihan and Akinci, Nurver and Karabag Yilmaz, Esra and Agbas, Ayse and Nayir, Ahmet Nevzat and Konukoglu, Dildar and Kurugoglu, Sebuh and Sever, Lale and Caliskan, Salim},\n\tmonth = feb,\n\tyear = {2024},\n\tkeywords = {Custom, Custom Panel, DDM, Nephropathies},\n}\n\n

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\n IntroductionIn the pediatric context, most children with autosomal dominant polycystic kidney disease (ADPKD) maintain a normal glomerular filtration rate (GFR) despite underlying structural kidney damage, highlighting the critical need for early intervention and predictive markers. Due to the inverse relationship between kidney volume and kidney function, risk assessments have been presented on the basis of kidney volume. The aim of this study was to use magnetic resonance imaging (MRI)-based kidney volume assessment for risk stratification in pediatric ADPKD and to investigate clinical and genetic differences among risk groups.MethodsThis multicenter, cross-sectional, and case-control study included 75 genetically confirmed pediatric ADPKD patients (5–18 years) and 27 controls. Kidney function was assessed by eGFR calculated from serum creatinine and cystatin C using the CKiD-U25 equation. Blood pressure was assessed by both office and 24-hour ambulatory measurements. Kidney volume was calculated from MRI using the stereological method. Total kidney volume was adjusted for the height (htTKV). Patients were stratified from A to E classes according to the Leuven Imaging Classification (LIC) using MRI-derived htTKV.ResultsMedian (Q1-Q3) age of the patients was 6.0 (2.0–10.0) years, 56% were male. There were no differences in sex, age, height-SDS, or GFR between the patient and control groups. Of the patients, 89% had PKD1 and 11% had PKD2 mutations. Non-missense mutations were 73% in PKD1 and 75% in PKD2. Twenty patients (27%) had hypertension based on ABPM. Median htTKV of the patients was significantly higher than controls (141 vs. 117 ml/m, p = 0.0003). LIC stratification revealed Classes A (38.7%), B (28%), C (24%), and D + E (9.3%). All children in class D + E and 94% in class C had PKD1 variants. Class D + E patients had significantly higher blood pressure values and hypertension compared to other classes (p \\textgreater 0.05 for all).DiscussionThis study distinguishes itself by using MRI-based measurements of kidney volume to stratify pediatric ADPKD patients into specific risk groups. It is important to note that PKD1 mutation and elevated blood pressure were higher in the high-risk groups stratified by age and kidney volume. Our results need to be confirmed in further studies.\n

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\n \n\n \n \n \n \n \n \n UroPredict: Machine learning model on real-world data for prediction of kidney cancer recurrence (UroCCR-120).\n \n \n \n \n\n\n \n Margue, G.; Ferrer, L.; Etchepare, G.; Bigot, P.; Bensalah, K.; Mejean, A.; Roupret, M.; Doumerc, N.; Ingels, A.; Boissier, R.; Pignot, G.; Parier, B.; Paparel, P.; Waeckel, T.; Colin, T.; and Bernhard, J.\n\n\n \n\n\n\n npj Precision Oncology, 8(1): 1–10. February 2024.\n Number: 1 Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"UroPredict:$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{margue_uropredict_2024,\n\ttitle = {{UroPredict}: {Machine} learning model on real-world data for prediction of kidney cancer recurrence ({UroCCR}-120)},\n\tvolume = {8},\n\tcopyright = {2024 The Author(s)},\n\tissn = {2397-768X},\n\tshorttitle = {{UroPredict}},\n\turl = {https://www.nature.com/articles/s41698-024-00532-x},\n\tdoi = {10.1038/s41698-024-00532-x},\n\tabstract = {Renal cell carcinoma (RCC) is most often diagnosed at a localized stage, where surgery is the standard of care. Existing prognostic scores provide moderate predictive performance, leading to challenges in establishing follow-up recommendations after surgery and in selecting patients who could benefit from adjuvant therapy. In this study, we developed a model for individual postoperative disease-free survival (DFS) prediction using machine learning (ML) on real-world prospective data. Using the French kidney cancer research network database, UroCCR, we analyzed a cohort of surgically treated RCC patients. Participating sites were randomly assigned to either the training or testing cohort, and several ML models were trained on the training dataset. The predictive performance of the best ML model was then evaluated on the test dataset and compared with the usual risk scores. In total, 3372 patients were included, with a median follow-up of 30 months. The best results in predicting DFS were achieved using Cox PH models that included 24 variables, resulting in an iAUC of 0.81 [IC95\\% 0.77–0.85]. The ML model surpassed the predictive performance of the most commonly used risk scores while handling incomplete data in predictors. Lastly, patients were stratified into four prognostic groups with good discrimination (iAUC = 0.79 [IC95\\% 0.74–0.83]). Our study suggests that applying ML to real-world prospective data from patients undergoing surgery for localized or locally advanced RCC can provide accurate individual DFS prediction, outperforming traditional prognostic scores.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2024-02-27},\n\tjournal = {npj Precision Oncology},\n\tauthor = {Margue, Gaëlle and Ferrer, Loïc and Etchepare, Guillaume and Bigot, Pierre and Bensalah, Karim and Mejean, Arnaud and Roupret, Morgan and Doumerc, Nicolas and Ingels, Alexandre and Boissier, Romain and Pignot, Géraldine and Parier, Bastien and Paparel, Philippe and Waeckel, Thibaut and Colin, Thierry and Bernhard, Jean-Christophe},\n\tmonth = feb,\n\tyear = {2024},\n\tnote = {Number: 1\nPublisher: Nature Publishing Group},\n\tkeywords = {Cohort, Multimodal, RCC, Risk factors, Surgical oncology, renal cell carcinoma},\n\tpages = {1--10},\n}\n\n

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\n \n\n \n \n \n \n \n \n Biphasic papillary (biphasic squamoid alveolar) renal cell carcinoma: a clinicopathologic and molecular study of 17 renal cell carcinomas including 10 papillary adenomas.\n \n \n \n \n\n\n \n Nova-Camacho, L. M.; Acosta, A. M.; Akgul, M.; Panizo, A.; Galea, L. A.; Val-Carreres, A.; Talavera, J. A.; Guerrero-Setas, D.; Martin-Arruti, M.; Ruiz, I.; García-Martos, M.; and Sangoi, A. R.\n\n\n \n\n\n\n Virchows Archiv. February 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"Biphasic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{nova-camacho_biphasic_2024,\n\ttitle = {Biphasic papillary (biphasic squamoid alveolar) renal cell carcinoma: a clinicopathologic and molecular study of 17 renal cell carcinomas including 10 papillary adenomas},\n\tissn = {1432-2307},\n\tshorttitle = {Biphasic papillary (biphasic squamoid alveolar) renal cell carcinoma},\n\turl = {https://doi.org/10.1007/s00428-024-03768-x},\n\tdoi = {10.1007/s00428-024-03768-x},\n\tabstract = {Biphasic papillary renal cell carcinoma (synonymous with biphasic squamoid alveolar renal cell carcinoma) is considered within the spectrum of papillary renal cell carcinoma (PRCC). With {\\textless} 70 reported cases of biphasic PRCC, there is limited data on the pathologic spectrum and clinical course. Seventeen biphasic PRCC cases and 10 papillary adenomas with similar biphasic morphology were assessed. The mean age of the biphasic PRCC patients was 62 years (male to female ratio of 1.8:1), from 10 partial nephrectomies, 6 radical nephrectomies, and 1 biopsy. The mean tumor size was 3.6 cm (range 1.6-8 cm), with 24\\% showing multifocality. Fifteen out of 17 cases were limited to the kidney (one of which was staged as pT2a but had lung metastases at diagnosis) and 2/17 cases were staged as T3a. All tumors showed typical biphasic morphology with an extent of squamoid foci widely variable from 10 to 95\\%. Emperipolesis was identified in 88\\% of cases. All biphasic PRCC tested exhibited positivity for PAX8 (16/16), keratin 7 (17/17), EMA (15/15), AMACR (17/17), and vimentin (12/12) in both large and small cells; cyclin D1 was only expressed in the large cells (16/16). The 10 papillary adenomas showed a similar immunoprofile to biphasic PRCC. NGS testing performed on 13 biphasic PRCC revealed 4 (31\\%) harboring MET SNVs. In 1/5 (20\\%) papillary adenomas, a pathogenic MET SNV was identified. Biphasic PRCC is rare with a generally similar immunoprofile to “type 1” PRCC but with notable strong positivity for cyclin D1 in the large cell component. Although most of the biphasic PRCC cases were of small size, low stage, and with an indolent behavior, one patient had metastatic disease and one patient died of the disease.},\n\tlanguage = {en},\n\turldate = {2024-02-27},\n\tjournal = {Virchows Archiv},\n\tauthor = {Nova-Camacho, Luiz M. and Acosta, Andres M. and Akgul, Mahmut and Panizo, Angel and Galea, Laurence A. and Val-Carreres, Andrea and Talavera, Juan A. and Guerrero-Setas, David and Martin-Arruti, Maialen and Ruiz, Irune and García-Martos, María and Sangoi, Ankur R.},\n\tmonth = feb,\n\tyear = {2024},\n\tkeywords = {Adenoma, Biphasic, Custom Cancer Panel, Custom STS, DDM, MET, PRCC, Papillary, RCC, Solid Tumor, Squamoid alveolar},\n}\n\n

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\n \n\n \n \n \n \n \n \n A retrospective study on the clinical and molecular outcomes of calpainopathy in a Turkish patient cohort.\n \n \n \n \n\n\n \n ŞAHİN, İ.; KARATAŞ, E.; DEMİR, M.; TAN, B.; PER, H.; ÖZKUL, Y.; and DÜNDAR, M.\n\n\n \n\n\n\n Turkish Journal of Medical Sciences, 54(1): 86–98. February 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{sahin_retrospective_2024,\n\ttitle = {A retrospective study on the clinical and molecular outcomes of calpainopathy in a {Turkish} patient cohort},\n\tvolume = {54},\n\tissn = {1300-0144},\n\turl = {https://journals.tubitak.gov.tr/medical/vol54/iss1/11},\n\tdoi = {10.55730/1300-0144.5769},\n\tnumber = {1},\n\tjournal = {Turkish Journal of Medical Sciences},\n\tauthor = {ŞAHİN, İzem and KARATAŞ, Emine and DEMİR, Mikail and TAN, Büşra and PER, Hüseyin and ÖZKUL, Yusuf and DÜNDAR, Munis},\n\tmonth = feb,\n\tyear = {2024},\n\tkeywords = {DDM, HDS, Hereditary Disorder Solution, LGMD2A, LGMDD1, LGMDR1, NGS sequencing},\n\tpages = {86--98},\n}\n\n

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\n \n\n \n \n \n \n \n \n Recombinant IFN-γ1b Treatment in a Patient with Inherited IFN-γ Deficiency.\n \n \n \n \n\n\n \n Rosain, J.; Kiykim, A.; Michev, A.; Kendir-Demirkol, Y.; Rinchai, D.; Peel, J. N.; Li, H.; Ocak, S.; Ozdemir, P. G.; Le Voyer, T.; Philippot, Q.; Khan, T.; Neehus, A.; Migaud, M.; Soudée, C.; Boisson-Dupuis, S.; Marr, N.; Borghesi, A.; Casanova, J.; and Bustamante, J.\n\n\n \n\n\n\n Journal of Clinical Immunology, 44(3): 62. February 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"Recombinant$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{rosain_recombinant_2024,\n\ttitle = {Recombinant {IFN}-γ1b {Treatment} in a {Patient} with {Inherited} {IFN}-γ {Deficiency}},\n\tvolume = {44},\n\tissn = {1573-2592},\n\turl = {https://doi.org/10.1007/s10875-024-01661-5},\n\tdoi = {10.1007/s10875-024-01661-5},\n\tabstract = {Inborn errors of IFN-γ immunity underlie Mendelian susceptibility to mycobacterial disease (MSMD). Twenty-two genes with products involved in the production of, or response to, IFN-γ and variants of which underlie MSMD have been identified. However, pathogenic variants of IFNG encoding a defective IFN-γ have been described in only two siblings, who both underwent hematopoietic stem cell transplantation (HCST).},\n\tlanguage = {en},\n\tnumber = {3},\n\turldate = {2024-02-23},\n\tjournal = {Journal of Clinical Immunology},\n\tauthor = {Rosain, Jérémie and Kiykim, Ayca and Michev, Alexandre and Kendir-Demirkol, Yasemin and Rinchai, Darawan and Peel, Jessica N. and Li, Hailun and Ocak, Suheyla and Ozdemir, Pinar Gokmirza and Le Voyer, Tom and Philippot, Quentin and Khan, Taushif and Neehus, Anna-Lena and Migaud, Mélanie and Soudée, Camille and Boisson-Dupuis, Stéphanie and Marr, Nico and Borghesi, Alessandro and Casanova, Jean-Laurent and Bustamante, Jacinta},\n\tmonth = feb,\n\tyear = {2024},\n\tkeywords = {BCG, CES, Clinical Exome, DDM, Inborn error of immunity, Interferon-gamma, Mycobacterium, clinical exome sequencing (CES)},\n\tpages = {62},\n}\n\n

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\n \n\n \n \n \n \n \n \n Natural history of ENPP1 deficiency: Nationwide Turkish Cohort Study of autosomal-recessive hypophosphataemic rickets type 2.\n \n \n \n \n\n\n \n Dursun, F.; Turan, İ.; Bitkin, E. Ç.; Bayramoğlu, E.; Çayır, A.; Erdeve, Ş. S.; Çakır, E. D. P.; Çamtosun, E.; Dilek, S. O.; Kırmızıbekmez, H.; Eser, M.; Türkyılmaz, A.; and Karagüzel, G.\n\n\n \n\n\n\n Clinical Endocrinology, n/a(n/a). February 2024.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/cen.15028\n\n\n\n
\n\n\n\n \n \n $\"Natural$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{dursun_natural_2024,\n\ttitle = {Natural history of {ENPP1} deficiency: {Nationwide} {Turkish} {Cohort} {Study} of autosomal-recessive hypophosphataemic rickets type 2},\n\tvolume = {n/a},\n\tcopyright = {© 2024 John Wiley \\& Sons Ltd.},\n\tissn = {1365-2265},\n\tshorttitle = {Natural history of {ENPP1} deficiency},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1111/cen.15028},\n\tdoi = {10.1111/cen.15028},\n\tabstract = {Objective Autosomal-recessive hypophosphataemic rickets type 2 (ARHR2) is a rare disease that is reported in survivors of generalized arterial calcification of infancy (GACI). Design, Patients and Measurement The objective of this study was to characterize a multicenter paediatric cohort with ARHR2 due to ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (ENPP1) deficiency and with a diagnosis of GACI or GACI-related findings. The clinical, biochemical and genetic characteristics of the patients were retrospectively retrieved. Results We identified 18 patients from 13 families diagnosed with ARHR2. Fifteen of the patients had an ENPP1 variation confirmed with genetic analyses, and three were siblings of one of these patients, who had clinically diagnosed hypophosphataemic rickets (HRs) with the same presentation. From nine centres, 18 patients, of whom 12 (66.7\\%) were females, were included in the study. The mean age at diagnosis was 4.2 ± 2.2 (1.6–9) years. The most frequently reported clinical findings on admission were limb deformities (66.6\\%) and short stature (44.4\\%). At diagnosis, the mean height SD was −2.2 ± 1.3. Five of the patients were diagnosed with GACI in the neonatal period and treated with bisphosphonates. Other patients were initially diagnosed with ARHR2, but after the detection of a biallelic variant in the ENPP1 gene, it was understood that they previously had clinical findings associated with GACI. Three patients had hearing loss, and two had cervical fusion. After the treatment of HRs, one patient developed calcification, and one developed intimal proliferation. Conclusion ARHR2 represents one manifestation of ENPP1 deficiency that usually manifests later in life than GACI. The history of calcifications or comorbidities that might be associated with GACI will facilitate the diagnosis in patients with ARHR2, and patients receiving calcitriol and phosphate medication should be carefully monitored for signs of calcification or intimal proliferation.},\n\tlanguage = {en},\n\tnumber = {n/a},\n\turldate = {2024-02-12},\n\tjournal = {Clinical Endocrinology},\n\tauthor = {Dursun, Fatma and Turan, İhsan and Bitkin, Eda Çelebi and Bayramoğlu, Elvan and Çayır, Atilla and Erdeve, Şenay Savaş and Çakır, Esra Deniz Papatya and Çamtosun, Emine and Dilek, Semine Ozdemir and Kırmızıbekmez, Heves and Eser, Metin and Türkyılmaz, Ayberk and Karagüzel, Gülay},\n\tmonth = feb,\n\tyear = {2024},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/cen.15028},\n\tkeywords = {DDM, ENPP1 deficiency, autosomal-recessive hypophosphataemic rickets type 2, generalized arterial calcification of infancy},\n}\n\n

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\n Objective Autosomal-recessive hypophosphataemic rickets type 2 (ARHR2) is a rare disease that is reported in survivors of generalized arterial calcification of infancy (GACI). Design, Patients and Measurement The objective of this study was to characterize a multicenter paediatric cohort with ARHR2 due to ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (ENPP1) deficiency and with a diagnosis of GACI or GACI-related findings. The clinical, biochemical and genetic characteristics of the patients were retrospectively retrieved. Results We identified 18 patients from 13 families diagnosed with ARHR2. Fifteen of the patients had an ENPP1 variation confirmed with genetic analyses, and three were siblings of one of these patients, who had clinically diagnosed hypophosphataemic rickets (HRs) with the same presentation. From nine centres, 18 patients, of whom 12 (66.7%) were females, were included in the study. The mean age at diagnosis was 4.2 ± 2.2 (1.6–9) years. The most frequently reported clinical findings on admission were limb deformities (66.6%) and short stature (44.4%). At diagnosis, the mean height SD was −2.2 ± 1.3. Five of the patients were diagnosed with GACI in the neonatal period and treated with bisphosphonates. Other patients were initially diagnosed with ARHR2, but after the detection of a biallelic variant in the ENPP1 gene, it was understood that they previously had clinical findings associated with GACI. Three patients had hearing loss, and two had cervical fusion. After the treatment of HRs, one patient developed calcification, and one developed intimal proliferation. Conclusion ARHR2 represents one manifestation of ENPP1 deficiency that usually manifests later in life than GACI. The history of calcifications or comorbidities that might be associated with GACI will facilitate the diagnosis in patients with ARHR2, and patients receiving calcitriol and phosphate medication should be carefully monitored for signs of calcification or intimal proliferation.\n

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\n \n\n \n \n \n \n \n \n ARTIFICIAL INTELLIGENCE IN HEALTHCARE: A REVIEW OF ETHICAL DILEMMAS AND PRACTICAL APPLICATIONS.\n \n \n \n \n\n\n \n Anyanwu, E. C.; Okongwu, C. C.; Olorunsogo, T. O.; Ayo-Farai, O.; Osasona, F.; and Daraojimba, O. D.\n\n\n \n\n\n\n International Medical Science Research Journal, 4(2): 126–140. February 2024.\n Number: 2\n\n\n\n
\n\n\n\n \n \n $\"ARTIFICIAL$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{anyanwu_artificial_2024,\n\ttitle = {{ARTIFICIAL} {INTELLIGENCE} {IN} {HEALTHCARE}: {A} {REVIEW} {OF} {ETHICAL} {DILEMMAS} {AND} {PRACTICAL} {APPLICATIONS}},\n\tvolume = {4},\n\tcopyright = {Copyright (c) 2024 Evangel Chinyere Anyanwu, Chiamaka Chinaemelum Okongwu, Tolulope O Olorunsogo, Oluwatoyin Ayo-Farai, Femi Osasona, Obinna Donald Daraojimba},\n\tissn = {2707-3408},\n\tshorttitle = {{ARTIFICIAL} {INTELLIGENCE} {IN} {HEALTHCARE}},\n\turl = {https://www.fepbl.com/index.php/imsrj/article/view/755},\n\tdoi = {10.51594/imsrj.v4i2.755},\n\tabstract = {The fusion of Artificial Intelligence (AI) and healthcare heralds a new era of innovation and transformation, yet it is not without its ethical quandaries. This comprehensive review traverses the intricate landscape where AI meets healthcare, delving into the ethical dilemmas that arise alongside practical applications. The ethical considerations span a spectrum, encompassing issues of patient privacy, transparency, accountability, and the inadvertent perpetuation of biases within AI algorithms. Privacy concerns emerge as a central ethical dilemma as healthcare providers leverage AI to process vast amounts of patient data. Striking a delicate balance between harnessing the power of AI for diagnostic and predictive purposes and safeguarding sensitive medical information is a critical challenge. Moreover, the review scrutinizes the ethical implications of AI algorithms and their potential to perpetuate biases, inadvertently exacerbating health disparities. A nuanced examination of bias mitigation strategies becomes imperative to ensure that AI technologies contribute to equitable healthcare outcomes. In tandem with ethical considerations, the review illuminates the practical applications reshaping the healthcare landscape. AI-driven diagnostics, predictive modeling, and personalized treatment plans emerge as transformative tools, enhancing clinical decision-making and patient outcomes. The efficient allocation of resources, streamlined workflows, and the acceleration of drug discovery processes showcase the tangible benefits of AI integration. This review aspires to guide healthcare practitioners, policymakers, and technologists in navigating the ethical crossroads of AI in healthcare. By fostering an awareness of ethical pitfalls and emphasizing responsible AI development, stakeholders can collaboratively shape a future where AI augments healthcare delivery, upholds ethical standards, and ultimately improves the quality of patient care.\nKeywords: \\&nbsp;AI, Healthcare, Ethics, Review, AI Application.},\n\tlanguage = {en},\n\tnumber = {2},\n\turldate = {2024-02-06},\n\tjournal = {International Medical Science Research Journal},\n\tauthor = {Anyanwu, Evangel Chinyere and Okongwu, Chiamaka Chinaemelum and Olorunsogo, Tolulope O. and Ayo-Farai, Oluwatoyin and Osasona, Femi and Daraojimba, Obinna Donald},\n\tmonth = feb,\n\tyear = {2024},\n\tnote = {Number: 2},\n\tkeywords = {DDM, artificial intelligence},\n\tpages = {126--140},\n}\n\n

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\n The fusion of Artificial Intelligence (AI) and healthcare heralds a new era of innovation and transformation, yet it is not without its ethical quandaries. This comprehensive review traverses the intricate landscape where AI meets healthcare, delving into the ethical dilemmas that arise alongside practical applications. The ethical considerations span a spectrum, encompassing issues of patient privacy, transparency, accountability, and the inadvertent perpetuation of biases within AI algorithms. Privacy concerns emerge as a central ethical dilemma as healthcare providers leverage AI to process vast amounts of patient data. Striking a delicate balance between harnessing the power of AI for diagnostic and predictive purposes and safeguarding sensitive medical information is a critical challenge. Moreover, the review scrutinizes the ethical implications of AI algorithms and their potential to perpetuate biases, inadvertently exacerbating health disparities. A nuanced examination of bias mitigation strategies becomes imperative to ensure that AI technologies contribute to equitable healthcare outcomes. In tandem with ethical considerations, the review illuminates the practical applications reshaping the healthcare landscape. AI-driven diagnostics, predictive modeling, and personalized treatment plans emerge as transformative tools, enhancing clinical decision-making and patient outcomes. The efficient allocation of resources, streamlined workflows, and the acceleration of drug discovery processes showcase the tangible benefits of AI integration. This review aspires to guide healthcare practitioners, policymakers, and technologists in navigating the ethical crossroads of AI in healthcare. By fostering an awareness of ethical pitfalls and emphasizing responsible AI development, stakeholders can collaboratively shape a future where AI augments healthcare delivery, upholds ethical standards, and ultimately improves the quality of patient care. Keywords: AI, Healthcare, Ethics, Review, AI Application.\n

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\n \n\n \n \n \n \n \n \n Spread Through Air Spaces in Stage I to III Resected Lung Adenocarcinomas: Should the Presence of Spread Through Air Spaces Lead to an Upstaging?.\n \n \n \n \n\n\n \n Laville, D.; Désage, A.; Fournel, P.; Bayle-Bleuez, S.; Neifer, C.; Picot, T.; Sulaiman, A.; Tiffet, O.; and Forest, F.\n\n\n \n\n\n\n The American Journal of Surgical Pathology,10.1097/PAS.0000000000002188. February 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"Spread$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{laville_spread_2024,\n\ttitle = {Spread {Through} {Air} {Spaces} in {Stage} {I} to {III} {Resected} {Lung} {Adenocarcinomas}: {Should} the {Presence} of {Spread} {Through} {Air} {Spaces} {Lead} to an {Upstaging}?},\n\tissn = {0147-5185},\n\tshorttitle = {Spread {Through} {Air} {Spaces} in {Stage} {I} to {III} {Resected} {Lung} {Adenocarcinomas}},\n\turl = {https://journals.lww.com/ajsp/abstract/9900/spread_through_air_spaces_in_stage_i_to_iii.297.aspx},\n\tdoi = {10.1097/PAS.0000000000002188},\n\tabstract = {In recent years, the concept of spread through air spaces (STAS) has been discussed as an adverse prognostic factor for lung cancer. The aim of our study is to clarify the prognostic role of STAS in relation to the main recognized prognostic factors in a retrospective cohort of 330 European patients who underwent stages I to III lung adenocarcinoma resection. On univariate analysis, the presence of STAS was related to progression-free survival (PFS; hazard ratio [HR]: 1.48; 95\\% CI: 1.02-2.19; P = 0.038) and overall survival (OS; HR: 1.61; 95\\% CI: 1.03-2.52; P = 0.50). On multivariate analysis, STAS was related to PFS (HR: 1.51; 95\\% CI: 1.00-2.17; P = 0.050) and to OS (HR: 1.67; 95\\% CI: 1.00-2.81; P = 0.050). We showed that the presence of STAS was associated with lower PFS, equivalent to the next pathologic T stage, especially the median PFS of T3 stages without STAS was at 62.8 months while the median PFS of T3 stages with STAS was at 15.7 months, closer to the median PFS of 17.4 months in T4 stages. To conclude, STAS is an independent prognostic factor of PFS in this European cohort and is close to significance for OS. We suggest that the presence of STAS might lead to an upstaging of lung adenocarcinoma.},\n\tlanguage = {en-US},\n\turldate = {2024-02-06},\n\tjournal = {The American Journal of Surgical Pathology},\n\tauthor = {Laville, David and Désage, Anne-Laure and Fournel, Pierre and Bayle-Bleuez, Sophie and Neifer, Chaouki and Picot, Tiphanie and Sulaiman, Abdulrazzak and Tiffet, Olivier and Forest, Fabien},\n\tmonth = feb,\n\tyear = {2024},\n\tkeywords = {Alamut, Lung Cancer, lung adenocarcinoma},\n\tpages = {10.1097/PAS.0000000000002188},\n}\n\n

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\n \n\n \n \n \n \n \n \n High-grade B-cell lymphoma mimicking a presentation of multiple myeloma.\n \n \n \n \n\n\n \n Chan, K.; and Salvaris, R.\n\n\n \n\n\n\n Pathology, 56: S98–S99. February 2024.\n Publisher: Elsevier\n\n\n\n
\n\n\n\n \n \n $\"High-grade$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{chan_high-grade_2024,\n\ttitle = {High-grade {B}-cell lymphoma mimicking a presentation of multiple myeloma},\n\tvolume = {56},\n\tissn = {0031-3025},\n\turl = {https://www.pathologyjournal.rcpa.edu.au/article/S0031-3025(23)00667-0/fulltext},\n\tdoi = {10.1016/j.pathol.2023.12.332},\n\tlanguage = {English},\n\turldate = {2024-02-01},\n\tjournal = {Pathology},\n\tauthor = {Chan, Kelvin and Salvaris, Ross},\n\tmonth = feb,\n\tyear = {2024},\n\tnote = {Publisher: Elsevier},\n\tkeywords = {MYS, Myeloid, Myeloid Solution},\n\tpages = {S98--S99},\n}\n\n

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\n \n\n \n \n \n \n \n \n Concordance between an FDA-approved companion diagnostic and an alternative assay kit for assessing homologous recombination deficiency in ovarian cancer.\n \n \n \n \n\n\n \n Wehn, A. K.; Qiu, P.; Lunceford, J.; Yarunin, A.; Cristescu, R.; Liu, L.; Roessler, K.; Bilke, S.; Day, J. R.; Timms, K. M.; Weichert, W.; and Marton, M. J.\n\n\n \n\n\n\n Gynecologic Oncology, 184: 67–73. January 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"Concordance$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{wehn_concordance_2024,\n\ttitle = {Concordance between an {FDA}-approved companion diagnostic and an alternative assay kit for assessing homologous recombination deficiency in ovarian cancer},\n\tvolume = {184},\n\tissn = {0090-8258},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0090825824000234},\n\tdoi = {10.1016/j.ygyno.2024.01.016},\n\tabstract = {Objective\nAuthors evaluated the performance of a commercially available next-generation sequencing assay kit; this was based on genomic content from Illumina's TruSight™ Oncology 500 research assay that identifies BRCA variants and proprietary algorithms licensed from Myriad and, with additional genomic content, measures the homologous recombination deficiency (HRD) genomic instability score (GIS) in tumor tissue (TSO 500 HRD assay).\nMethods\nData from the TSO 500 HRD assay were compared with data from the Myriad MyChoice®CDx PLUS assay (Myriad assay). Prevalence rates for overall HRD status and BRCA mutations (a deleterious or suspected deleterious BRCA1 or BRCA2 mutation or both) and assay agreement rates for HRD GIS and BRCA analysis were assessed in ovarian tumor samples. Pearson correlations of the continuous HRD GIS and analytic sensitivity and specificity were evaluated.\nResults\nThe prevalence of overall HRD positivity was 51.2\\% (TSO 500 HRD assay) versus 49.2\\% (Myriad assay) and the prevalence of BRCA mutations was 27.6\\% (TSO 500 HRD assay) versus 25.5\\% (Myriad assay). After post-processing optimization, concordance of the HRD GIS was 0.980 in all samples and 0.976 in the non-BRCA mutation cohort; the area under the receiver operating characteristic curve was 0.995 and 0.992, respectively.\nConclusions\nComparison between the Illumina and Myriad assays showed that overall HRD status, the individual components of BRCA analysis, and HRD GIS detection results were highly concordant ({\\textgreater}93\\%), suggesting the TSO 500 HRD assay will approach the analytical accuracy of the FDA-approved Myriad assay.},\n\turldate = {2024-02-01},\n\tjournal = {Gynecologic Oncology},\n\tauthor = {Wehn, Amy K. and Qiu, Ping and Lunceford, Jared and Yarunin, Alexander and Cristescu, Razvan and Liu, Li and Roessler, Kyria and Bilke, Sven and Day, John R. and Timms, Kirsten M. and Weichert, Wilko and Marton, Matthew J.},\n\tmonth = jan,\n\tyear = {2024},\n\tkeywords = {BRCA, Genomic instability score, HRD, Homologous recombination deficiency, Ovarian cancer},\n\tpages = {67--73},\n}\n\n

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\n \n\n \n \n \n \n \n \n Identification of novel and de novo variant in the SCN1A gene confirms Dravet syndrome in Moroccan child: a case report.\n \n \n \n \n\n\n \n El Mouhi, H.; Amllal, N.; Abbassi, M.; Nedbour, A.; Jalte, M.; Lyahyai, J.; Chafai Elalaoui, S.; Bouguenouch, L.; and Chaouki, S.\n\n\n \n\n\n\n Molecular Biology Reports, 51(1): 233. January 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"Identification$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{el_mouhi_identification_2024,\n\ttitle = {Identification of novel and de novo variant in the {SCN1A} gene confirms {Dravet} syndrome in {Moroccan} child: a case report},\n\tvolume = {51},\n\tissn = {1573-4978},\n\tshorttitle = {Identification of novel and de novo variant in the {SCN1A} gene confirms {Dravet} syndrome in {Moroccan} child},\n\turl = {https://doi.org/10.1007/s11033-023-09200-y},\n\tdoi = {10.1007/s11033-023-09200-y},\n\tabstract = {Dravet syndrome is a severe form of epilepsy characterised by recurrent seizures and cognitive impairment. It is mainly caused by variant in the SCN1A gene in 90\\% of cases, which codes for the α subunit of the voltage-gated sodium channel. In this study, we present one suspected case of Dravet syndrome in Moroccan child that underwent exome analysis and were confirmed by Sanger sequencing. The variant was identified in the SCN1A gene, and is a new variant that has never been described in the literature. The variant was found de nova in our case, indicating that it was not inherited from the parents. The variant, SCN1A c.965-2A{\\textgreater}G p.(?), is located at the splice site and results in an unknown modification of the protein. This variant is considered pathogenic on the basis of previous studies. These results contribute to our knowledge of the SCN1A gene mutations associated with Dravet syndrome and underline the importance of genetic analysis in the diagnosis and confirmation of this disorder. Further studies are needed to better understand the functional consequences of this variant and its implications for therapeutic strategies in Dravet syndrome.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2024-02-01},\n\tjournal = {Molecular Biology Reports},\n\tauthor = {El Mouhi, Hinde and Amllal, Nada and Abbassi, Meriame and Nedbour, Ayoub and Jalte, Meryem and Lyahyai, Jaber and Chafai Elalaoui, Siham and Bouguenouch, Laila and Chaouki, Sana},\n\tmonth = jan,\n\tyear = {2024},\n\tkeywords = {De nova variant, Dravet syndrome, Exome, Exome analysis, Exome sequencing, Novel variant, SCN1A gene, Sanger sequencing},\n\tpages = {233},\n}\n\n

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\n \n\n \n \n \n \n \n \n Follow-up of potential germline variants detected by next generation sequencing (NGS) in patients with myeloid neoplasms in Western Australia.\n \n \n \n \n\n\n \n Sekaran, U. C.\n\n\n \n\n\n\n Pathology, 56: S99. February 2024.\n Publisher: Elsevier\n\n\n\n
\n\n\n\n \n \n $\"Follow-up$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{sekaran_follow-up_2024,\n\ttitle = {Follow-up of potential germline variants detected by next generation sequencing ({NGS}) in patients with myeloid neoplasms in {Western} {Australia}},\n\tvolume = {56},\n\tissn = {0031-3025},\n\turl = {https://www.pathologyjournal.rcpa.edu.au/article/S0031-3025(23)00668-2/fulltext},\n\tdoi = {10.1016/j.pathol.2023.12.333},\n\tlanguage = {English},\n\turldate = {2024-02-01},\n\tjournal = {Pathology},\n\tauthor = {Sekaran, Usha Chandra},\n\tmonth = feb,\n\tyear = {2024},\n\tnote = {Publisher: Elsevier},\n\tkeywords = {MYS, Myeloid Solution},\n\tpages = {S99},\n}\n\n

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\n \n\n \n \n \n \n \n \n Comparison of Literature Mining Tools for Variant Classification: Through the Lens of Fifty RYR1 Variants.\n \n \n \n \n\n\n \n Wermers, Z.; Yoo, S.; Radenbaugh, B.; Douglass, A.; Biesecker, L. G.; and Johnston, J. J.\n\n\n \n\n\n\n Genetics in Medicine,101083. January 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"Comparison$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{wermers_comparison_2024,\n\ttitle = {Comparison of {Literature} {Mining} {Tools} for {Variant} {Classification}: {Through} the {Lens} of {Fifty} {RYR1} {Variants}},\n\tissn = {1098-3600},\n\tshorttitle = {Comparison of {Literature} {Mining} {Tools} for {Variant} {Classification}},\n\turl = {https://www.sciencedirect.com/science/article/pii/S1098360024000169},\n\tdoi = {10.1016/j.gim.2024.101083},\n\tabstract = {Purpose\nThe American College of Medical Genetics and Genomics and the Association for Molecular Pathology have outlined a schema that allows for systematic classification of variant pathogenicity. While gnomAD is generally accepted as a reliable source of population frequency data and ClinGen has provided guidance on the utility of specific bioinformatic predictors, there is not a consensus source for identifying publications relevant to a variant. Multiple tools are available to aid in the identification of relevant variant literature including manually curated databases and literature search engines. We set out to determine the utility of four literature mining tools used for ascertainment to inform the discussion of the use of these tools.\nMethods\nFour literature mining tools including the Human Gene Mutation Database, Mastermind®, ClinVar, and LitVar 2.0 were used to identify relevant variant literature for 50 RYR1 variants. Sensitivity and precision were determined for each tool.\nResults\nSensitivity among the four tools ranged from 0.332 to 0.687. Precision ranged from 0.389 to 0.906. No single tool retrieved all relevant publications.\nConclusion\nAt the current time, the use of multiple tools is necessary to completely identify the literature relevant to curate a variant.},\n\turldate = {2024-01-31},\n\tjournal = {Genetics in Medicine},\n\tauthor = {Wermers, Zara and Yoo, Seeley and Radenbaugh, Bailey and Douglass, Amber and Biesecker, Leslie G. and Johnston, Jennifer J.},\n\tmonth = jan,\n\tyear = {2024},\n\tkeywords = {ACMG guidelines, Alamut, Alamut Software v.2.15, Alamut Visual v.2.15, RYR1, biocuration, literature mining, variant classification},\n\tpages = {101083},\n}\n\n

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\n \n\n \n \n \n \n \n \n Association Between Cytometric Biomarkers, Clinical Phenotype, and Complications of Common Variable Immunodeficiency.\n \n \n \n \n\n\n \n Markocsy, A.; Bobcakova, A.; Petrovicova, O.; Kapustova, L.; Jurkova, E. M.; Schniederova, M.; Petriskova, J.; Cibulka, M.; Hyblova, M.; Jesenak, M.; Markocsy, A.; Bobcakova, A.; Petrovicova, O.; Kapustova, L.; Jurkova, E. M.; Barnova, M.; Petriskova, J.; Cibulka, M.; Hyblova, M.; and Jesenak, M.\n\n\n \n\n\n\n Cureus, 16(1). January 2024.\n Publisher: Cureus\n\n\n\n
\n\n\n\n \n \n $\"Association$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{markocsy_association_2024,\n\ttitle = {Association {Between} {Cytometric} {Biomarkers}, {Clinical} {Phenotype}, and {Complications} of {Common} {Variable} {Immunodeficiency}},\n\tvolume = {16},\n\tissn = {2168-8184},\n\turl = {https://www.cureus.com/articles/219964-association-between-cytometric-biomarkers-clinical-phenotype-and-complications-of-common-variable-immunodeficiency},\n\tdoi = {10.7759/cureus.52941},\n\tabstract = {Background: Common variable immunodeficiency (CVID) is a heterogeneous group of immune disorders. The patients are classified according to the clinical manifestation with the infection-only phenotype (CVIDinf) and CVID with immune dysregulation (CVIDid).\n\nMethods: We performed a retrospective clinical analysis of 64 CVID patients (34 males, 53.13\\%; mean age: 41.4 years; SD: ±21.4 years). We divided the patients into subgroups according to the clinical manifestation (CVIDinf and CVIDid) and according to B cell phenotypic profiling after performing flow cytometry with the use of the EUROclass classification. We compared clinical manifestations, selected laboratory parameters, and therapy in these groups. All CVIDid patients were tested after the manifestation of complications associated with immune dysregulation and in eight patients during the immunosuppressive treatment (systemic corticosteroids and hydroxychloroquine).\n\nResults: Two-thirds of patients in our cohort had symptoms resulting from immune dysregulation. Almost half of the patients had autoimmune complications. A higher proportion of marginal zone B cells was associated with autoimmune complications. A lower percentage of naïve B cells was connected to autoimmunity, whereas a lower proportion of transitional B cells was associated with rheumatic diseases and splenomegaly. Patients with lymphadenopathy had a higher percentage of double-negative T cells and a lower percentage of switched memory B cells. We performed molecular-genetic testing in 28\\% (n = 17) of patients and found a causal pathogenic variant in 23.5\\% (n = 4) of this group.\n\nConclusion: Based on our results, there is an association between specific cytometric parameters, clinical phenotype, and complications of CVID. The use of the subpopulations of B cells can be helpful in the diagnosis of these specific clinical complications in CVID patients and could help to personalise the therapeutic approach.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2024-01-31},\n\tjournal = {Cureus},\n\tauthor = {Markocsy, Adam and Bobcakova, Anna and Petrovicova, Otilia and Kapustova, Lenka and Jurkova, Eva Malicherova and Schniederova, Martina and Petriskova, Jela and Cibulka, Michal and Hyblova, Michaela and Jesenak, Milos and Markocsy, Adam and Bobcakova, Anna and Petrovicova, Otilia and Kapustova, Lenka and Jurkova, Eva Malicherova and Barnova, Martina and Petriskova, Jela and Cibulka, Michal and Hyblova, Michaela and Jesenak, Milos},\n\tmonth = jan,\n\tyear = {2024},\n\tnote = {Publisher: Cureus},\n\tkeywords = {CES v3, Clinical Exome, Clinical Exome Solution v3, DDM, b cell phenotypic profiling, common variable immunodeficiency, immune dysregulation, transitional b cells},\n}\n\n

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\n \n\n \n \n \n \n \n \n Genomic classification and outcomes of young patients with polycythemia vera and essential thrombocythemia according to the presence of splanchnic vein thrombosis and its chronology.\n \n \n \n \n\n\n \n Garrote, M.; López-Guerra, M.; García-Pagán, J. C.; Arellano-Rodrigo, E.; Ferrer-Marín, F.; Hernández-Boluda, J. C.; Bellosillo, B.; Nomdedeu, M.; Hernández-Gea, V.; Triguero, A.; Guijarro, F.; Álamo, J.; Baiges, A.; Turon, F.; Colomer, D.; Cervantes, F.; and Alvarez-Larrán, A.\n\n\n \n\n\n\n Annals of Hematology. January 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"Genomic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{garrote_genomic_2024,\n\ttitle = {Genomic classification and outcomes of young patients with polycythemia vera and essential thrombocythemia according to the presence of splanchnic vein thrombosis and its chronology},\n\tissn = {1432-0584},\n\turl = {https://doi.org/10.1007/s00277-023-05610-x},\n\tdoi = {10.1007/s00277-023-05610-x},\n\tabstract = {To elucidate the role of splanchnic vein thrombosis (SVT) and genomic characteristics in prognosis and survival, we compared patients with polycythemia vera (PV) or essential thrombocythemia (ET) presenting SVT at diagnosis (n = 69, median age 43 years) or during follow-up (n = 21, median age 46 years) to a sex- and age-matched control group of PV/ET without SVT (n = 165, median age 48 years). The majority of patients presenting with SVT at diagnosis were classified as myeloproliferative neoplasm with heterozygous JAK2 mutation (87\\% of cases vs. 69\\% in PV/ET control group, p {\\textless} 0.05), characterized by low JAK2 allele burden and no high-risk mutations. Despite this lower molecular complexity, patients presenting with SVT showed a higher risk of death (HR 3.0, 95\\% CI 1.5-6.0, p = 0.003) and lower event-free survival (HR 3.0, 95\\% CI 1.9–4.8, p {\\textless} 0.001) than age- and sex-matched PV/ET controls. In patients presenting with SVT, molecular high-risk was associated with increased risk of venous re-thrombosis (HR 5.8, 95\\% CI 1.4–24.0, p = 0.01). Patients developing SVT during follow-up were more frequently allocated in molecular high-risk than those with SVT at diagnosis (52\\% versus 13\\%, p {\\textless} 0.05). In the whole cohort of patients, molecular classification identified PV/ET patients at higher risk of disease progression whereas DNMT3A/TET2/ASXL1 mutations were associated with higher risk of arterial thrombosis. In conclusion, clinical and molecular characteristics are different in PV/ET patients with SVT, depending on whether it occurs at diagnosis or at follow-up. Molecular characterization by NGS is useful for assessing the risk of thrombosis and disease progression in young patients with PV/ET.},\n\tlanguage = {en},\n\turldate = {2024-01-29},\n\tjournal = {Annals of Hematology},\n\tauthor = {Garrote, Marta and López-Guerra, Mónica and García-Pagán, Juan Carlos and Arellano-Rodrigo, Eduardo and Ferrer-Marín, Francisca and Hernández-Boluda, Juan Carlos and Bellosillo, Beatriz and Nomdedeu, Meritxell and Hernández-Gea, Virginia and Triguero, Ana and Guijarro, Francesca and Álamo, José and Baiges, Anna and Turon, Fanny and Colomer, Dolors and Cervantes, Francisco and Alvarez-Larrán, Alberto},\n\tmonth = jan,\n\tyear = {2024},\n\tkeywords = {Custom Panel, DDM, Splanchnic vein thrombosis (SVT)},\n}\n\n

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\n \n\n \n \n \n \n \n CRISPR activation to characterize splice-altering variants in easily accessible cells.\n \n \n \n\n\n \n Terkelsen, T.; Mikkelsen, N. S.; Bak, E. N.; Vad-Nielsen, J.; Blechingberg, J.; Weiss, S.; Drue, S. O.; Andersen, H.; Andresen, B. S.; Bak, R. O.; and Jensen, U. B.\n\n\n \n\n\n\n American Journal of Human Genetics,S0002–9297(23)00478–0. January 2024.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{terkelsen_crispr_2024,\n\ttitle = {{CRISPR} activation to characterize splice-altering variants in easily accessible cells},\n\tissn = {1537-6605},\n\tdoi = {10.1016/j.ajhg.2023.12.024},\n\tabstract = {Genetic variants that affect mRNA splicing are a major cause of hereditary disorders, but the spliceogenicity of variants is challenging to predict. RNA diagnostics of clinically accessible tissues enable rapid functional characterization of splice-altering variants within their natural genetic context. However, this analysis cannot be offered to all individuals as one in five human disease genes are not expressed in easily accessible cell types. To overcome this problem, we have used CRISPR activation (CRISPRa) based on a dCas9-VPR mRNA-based delivery platform to induce expression of the gene of interest in skin fibroblasts from individuals with suspected monogenic disorders. Using this ex vivo splicing assay, we characterized the splicing patterns associated with germline variants in the myelin protein zero gene (MPZ), which is exclusively expressed in Schwann cells of the peripheral nerves, and the spastin gene (SPAST), which is predominantly expressed in the central nervous system. After overnight incubation, CRISPRa strongly upregulated MPZ and SPAST transcription in skin fibroblasts, which enabled splice variant profiling using reverse transcription polymerase chain reaction, next-generation sequencing, and long-read sequencing. Our investigations show proof of principle of a promising genetic diagnostic tool that involves CRISPRa to activate gene expression in easily accessible cells to study the functional impact of genetic variants. The procedure is easy to perform in a diagnostic laboratory with equipment and reagents all readily available.},\n\tlanguage = {eng},\n\tjournal = {American Journal of Human Genetics},\n\tauthor = {Terkelsen, Thorkild and Mikkelsen, Nanna Steengaard and Bak, Ebbe Norskov and Vad-Nielsen, Johan and Blechingberg, Jenny and Weiss, Simone and Drue, Simon Opstrup and Andersen, Henning and Andresen, Brage Storstein and Bak, Rasmus O. and Jensen, Uffe Birk},\n\tmonth = jan,\n\tyear = {2024},\n\tpmid = {38272032},\n\tkeywords = {Alamut, Alamut Visual Plus, CRISPR activation, clinical genetics, easily accessible cells, functional study, splice-altering variants},\n\tpages = {S0002--9297(23)00478--0},\n}\n\n

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\n \n\n \n \n \n \n \n \n A recurrent synonymous L1CAM variant in a fetus with hydrocephalus.\n \n \n \n \n\n\n \n Šubrt, I.; Zavoral, T.; Strych, L.; Černá, M.; Hejnalová, M.; Komrsková, P.; and Tejcová, J.\n\n\n \n\n\n\n Human Genome Variation, 11(1): 1–4. January 2024.\n Number: 1 Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{subrt_recurrent_2024,\n\ttitle = {A recurrent synonymous {L1CAM} variant in a fetus with hydrocephalus},\n\tvolume = {11},\n\tcopyright = {2024 The Author(s)},\n\tissn = {2054-345X},\n\turl = {https://www.nature.com/articles/s41439-024-00263-2},\n\tdoi = {10.1038/s41439-024-00263-2},\n\tabstract = {We report the case of a hydrocephalic fetus in which clinical exome sequencing revealed a recurrent synonymous variant of unknown significance, c.453G{\\textgreater}T, in the L1CAM gene. This report presents the second case of X-linked hydrocephalus in a fetus with this variant. Since we reproduced the RNA analysis, we were able to reclassify this variant as likely pathogenic. Our results stress the importance of not excluding synonymous variants during prioritization.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2024-01-29},\n\tjournal = {Human Genome Variation},\n\tauthor = {Šubrt, Ivan and Zavoral, Tomáš and Strych, Lukáš and Černá, Monika and Hejnalová, Markéta and Komrsková, Pavla and Tejcová, Jitka},\n\tmonth = jan,\n\tyear = {2024},\n\tnote = {Number: 1\nPublisher: Nature Publishing Group},\n\tkeywords = {CES v2, Clinical Exome Solution v2, Genetic testing, Next-generation sequencing, RNA splicing, clinical exome sequencing},\n\tpages = {1--4},\n}\n\n

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\n \n\n \n \n \n \n \n \n Germline mutational variants of Turkish ovarian cancer patients suspected of Hereditary Breast and Ovarian Cancer (HBOC) by next-generation sequencing.\n \n \n \n \n\n\n \n Tuncer, S. B.; Celik, B.; Erciyas, S. K.; Erdogan, O. S.; Gültaslar, B. K.; Odemis, D. A.; Avsar, M.; Sen, F.; Saip, P. M.; and Yazici, H.\n\n\n \n\n\n\n Pathology - Research and Practice, 254: 155075. January 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"Germline$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{tuncer_germline_2024,\n\ttitle = {Germline mutational variants of {Turkish} ovarian cancer patients suspected of {Hereditary} {Breast} and {Ovarian} {Cancer} ({HBOC}) by next-generation sequencing},\n\tvolume = {254},\n\tissn = {0344-0338},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0344033823007768},\n\tdoi = {10.1016/j.prp.2023.155075},\n\tabstract = {Hereditary Breast and Ovarian Cancer (HBOC) syndrome is characterized by an increased risk of developing breast cancer (BC) and ovarian cancer (OC) due to inherited genetic mutations. Understanding the genetic variants associated with HBOC is crucial for identifying individuals at high risk and implementing appropriate preventive measures. The study included 630 Turkish OC patients with confirmed diagnostic criteria of The National Comprehensive Cancer Network (NCCN) concerning HBOC. Genomic DNA was extracted from peripheral blood samples, and targeted Next-generation sequencing (NGS) was performed. Bioinformatics analysis and variant interpretation were conducted to identify pathogenic variants (PVs). Our analysis revealed a spectrum of germline pathogenic variants associated with HBOC in Turkish OC patients. Notably, several pathogenic variants in BRCA1, BRCA2, and other DNA repair genes were identified. Specifically, we observed germline PVs in 130 individuals, accounting for 20.63\\% of the total cohort. 76 distinct PVs in genes, BRCA1 (40 PVs), BRCA2 (29 PVs), ATM (1 PV), CHEK2 (2 PVs), ERCC2 (1 PV), MUTYH (1 PV), RAD51C (1 PV), and TP53 (1PV) and also, two different PVs (i.e., c.135–2 A{\\textgreater}G p.? in BRCA1 and c.6466\\_6469delTCTC in BRCA2) were detected in a 34-year-old OC patient. In conclusion, our study contributes to a better understanding of the genetic variants underlying HBOC in Turkish OC patients. These findings provide valuable insights into the genetic architecture of HBOC in the Turkish population and shed light on the potential contribution of specific germline PVs to the increased risk of OC.},\n\turldate = {2024-01-25},\n\tjournal = {Pathology - Research and Practice},\n\tauthor = {Tuncer, Seref Bugra and Celik, Betul and Erciyas, Seda Kilic and Erdogan, Ozge Sukruoglu and Gültaslar, Busra Kurt and Odemis, Demet Akdeniz and Avsar, Mukaddes and Sen, Fatma and Saip, Pınar Mualla and Yazici, Hulya},\n\tmonth = jan,\n\tyear = {2024},\n\tkeywords = {BRCA1/BRCA2, DDM, Germline Mutations, HBOC, HCS, Hereditary Cancer Solution, Multigene panels, NGS, Ovarian cancer},\n\tpages = {155075},\n}\n\n

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\n \n\n \n \n \n \n \n \n Clinical and Molecular Characterization of Mucopolysaccharidosis Type 3A and 3B in a Turkish Series.\n \n \n \n \n\n\n \n Noyan, B.; Elcioglu, N. H.; Tebani, A.; and Bekri, S.\n\n\n \n\n\n\n Molecular Syndromology,1–8. January 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"Clinical$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{noyan_clinical_2024,\n\ttitle = {Clinical and {Molecular} {Characterization} of {Mucopolysaccharidosis} {Type} {3A} and {3B} in a {Turkish} {Series}},\n\tissn = {1661-8769},\n\turl = {https://doi.org/10.1159/000535888},\n\tdoi = {10.1159/000535888},\n\tabstract = {Introduction: Sanfilippo syndrome or mucopolysaccharidosis type 3 (MPS-3) is a rare condition and its epidemiological data are still not defined. MPS-3 is linked to a deficiency in enzymes involved in heparan sulfate degradation. This biomolecule is neurotoxic and its accumulation underlies the severe central nervous system degeneration observed in this disease. Methods: Here, we describe 15 Turkish patients with MPS-3A or MPS-3B subtypes. Clinical data upon the diagnosis and during the follow-up as well as molecular characterization are reported. Results: Two and ten distinct variants were identified in SGSH and NAGLU gene sequences, respectively. Six variants (NAGLU NM\\_000263.3:c.532−?\\_c.764+?del, NAGLU NM\\_000263.3: c.509G\\&gt;T, NAGLU NM\\_000263.3: c.700C\\&gt;G, NAGLU NM\\_000263.3:c.507\\_516 del, NAGLU NM dises\\_000263.3: c.1354 G\\&gt;A, NAGLU NM\\_000263.3: c.200T\\&gt;C) have been previously published and 6 are novel (SGSH NM\\_000199.4: c.80T\\&gt;G, SGSH NM\\_000199.4: c.7\\_16del, NAGLU NM\\_000263.3: c.224\\_235del, NAGLU NM\\_000263.3: c.904G\\&gt;T, NAGLU NM\\_000263.3: c.626C\\&gt;T, NAGLU NM\\_000263.3: c.1241A\\&gt;G). SGSH NM\\_000199.4:c.7\\_16del variation might be caused by a founder effect. Conclusion: Due to the high rate of consanguinity in Turkey, the incidence of Sanfilippo syndrome might be higher compared to other populations worldwide. Our results contribute to the characterization of rare diseases in Turkey and to improve our knowledge of the clinical, molecular, and epidemiological aspects of MPS-3 disease.},\n\turldate = {2024-01-25},\n\tjournal = {Molecular Syndromology},\n\tauthor = {Noyan, Bilge and Elcioglu, Nursel H. and Tebani, Abdellah and Bekri, Soumeya},\n\tmonth = jan,\n\tyear = {2024},\n\tkeywords = {Alamut Batch, mucopolysaccharidosis},\n\tpages = {1--8},\n}\n\n

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\n \n\n \n \n \n \n \n \n Idiopathic erythrocytosis: a germline disease?.\n \n \n \n \n\n\n \n Elli, E. M.; Mauri, M.; D’Aliberti, D.; Crespiatico, I.; Fontana, D.; Redaelli, S.; Pelucchi, S.; Spinelli, S.; Manghisi, B.; Cavalca, F.; Aroldi, A.; Ripamonti, A.; Ferrari, S.; Palamini, S.; Mottadelli, F.; Massimino, L.; Ramazzotti, D.; Cazzaniga, G.; Piperno, A.; Gambacorti-Passerini, C.; and Piazza, R.\n\n\n \n\n\n\n Clinical and Experimental Medicine, 24(1): 11. January 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"Idiopathic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{elli_idiopathic_2024,\n\ttitle = {Idiopathic erythrocytosis: a germline disease?},\n\tvolume = {24},\n\tissn = {1591-9528},\n\tshorttitle = {Idiopathic erythrocytosis},\n\turl = {https://doi.org/10.1007/s10238-023-01283-y},\n\tdoi = {10.1007/s10238-023-01283-y},\n\tabstract = {Polycythemia Vera (PV) is typically caused by V617F or exon 12 JAK2 mutations. Little is known about Polycythemia cases where no JAK2 variants can be detected, and no other causes identified. This condition is defined as idiopathic erythrocytosis (IE). We evaluated clinical-laboratory parameters of a cohort of 56 IE patients and we determined their molecular profile at diagnosis with paired blood/buccal-DNA exome-sequencing coupled with a high-depth targeted OncoPanel to identify a possible underling germline or somatic cause. We demonstrated that most of our cohort (40/56: 71.4\\%) showed no evidence of clonal hematopoiesis, suggesting that IE is, in large part, a germline disorder. We identified 20 low mutation burden somatic variants (Variant allelic fraction, VAF, {\\textless} 10\\%) in only 14 (25\\%) patients, principally involving DNMT3A and TET2. Only 2 patients presented high mutation burden somatic variants, involving DNMT3A, TET2, ASXL1 and WT1. We identified recurrent germline variants in 42 (75\\%) patients occurring mainly in JAK/STAT, Hypoxia and Iron metabolism pathways, among them: JAK3-V722I and HIF1A-P582S; a high fraction of patients (48.2\\%) resulted also mutated in homeostatic iron regulatory gene HFE-H63D or C282Y. By generating cellular models, we showed that JAK3-V722I causes activation of the JAK-STAT5 axis and upregulation of EPAS1/HIF2A, while HIF1A-P582S causes suppression of hepcidin mRNA synthesis, suggesting a major role for these variants in the onset of IE.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2024-01-24},\n\tjournal = {Clinical and Experimental Medicine},\n\tauthor = {Elli, E. M. and Mauri, M. and D’Aliberti, D. and Crespiatico, I. and Fontana, D. and Redaelli, S. and Pelucchi, S. and Spinelli, S. and Manghisi, B. and Cavalca, F. and Aroldi, A. and Ripamonti, A. and Ferrari, S. and Palamini, S. and Mottadelli, F. and Massimino, L. and Ramazzotti, D. and Cazzaniga, G. and Piperno, A. and Gambacorti-Passerini, C. and Piazza, R.},\n\tmonth = jan,\n\tyear = {2024},\n\tkeywords = {DDM, Erythropoiesis, Idiopathic erythrocytosis, MYS, Myeloid Neoplasia, Myeloid Solution, NGS sequencing},\n\tpages = {11},\n}\n\n

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\n \n\n \n \n \n \n \n \n Prevalence and Distribution of MUTYH Pathogenic Variants, Is There a Relation with an Increased Risk of Breast Cancer?.\n \n \n \n \n\n\n \n Peña-López, J.; Jiménez-Bou, D.; Ruíz-Gutiérrez, I.; Martín-Montalvo, G.; Alameda-Guijarro, M.; Rueda-Lara, A.; Ruíz-Giménez, L.; Higuera-Gómez, O.; Gallego, A.; Pertejo-Fernández, A.; Sánchez-Cabrero, D.; Feliu, J.; and Rodríguez-Salas, N.\n\n\n \n\n\n\n Cancers, 16(2): 315. January 2024.\n Number: 2 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Prevalence$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{pena-lopez_prevalence_2024,\n\ttitle = {Prevalence and {Distribution} of {MUTYH} {Pathogenic} {Variants}, {Is} {There} a {Relation} with an {Increased} {Risk} of {Breast} {Cancer}?},\n\tvolume = {16},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2072-6694},\n\turl = {https://www.mdpi.com/2072-6694/16/2/315},\n\tdoi = {10.3390/cancers16020315},\n\tabstract = {Background: MUTYH has been implicated in hereditary colonic polyposis and colorectal carcinoma. However, there are conflicting data refgarding its relationship to hereditary breast cancer. Therefore, we aimed to assess if MUTYH mutations contribute to breast cancer susceptibility. Methods: We retrospectively reviewed 3598 patients evaluated from June 2018 to June 2023 at the Hereditary Cancer Unit of La Paz University Hospital, focusing on those with detected MUTYH variants. Results: Variants of MUTYH were detected in 56 patients (1.6\\%, 95\\%CI: 1.2–2.0). Of the 766 patients with breast cancer, 14 patients were carriers of MUTYH mutations (1.8\\%, 95\\%CI: 0.5–3.0). The prevalence of MUTYH mutation was significantly higher in the subpopulation with colonic polyposis (11.3\\% vs. 1.1\\%, p {\\textless} 0.00001, OR = 11.2, 95\\%CI: 6.2–22.3). However, there was no significant difference in the prevalence within the subpopulation with breast cancer (1.8\\% vs. 1.5\\%, p = 0.49, OR = 1.2, 95\\%CI: 0.7–2.3). Conclusion: In our population, we could not establish a relationship between MUTYH and breast cancer. These findings highlight the necessity for a careful interpretation when assessing the role of MUTYH mutations in breast cancer risk.},\n\tlanguage = {en},\n\tnumber = {2},\n\turldate = {2024-01-24},\n\tjournal = {Cancers},\n\tauthor = {Peña-López, Jesús and Jiménez-Bou, Diego and Ruíz-Gutiérrez, Icíar and Martín-Montalvo, Gema and Alameda-Guijarro, María and Rueda-Lara, Antonio and Ruíz-Giménez, Leticia and Higuera-Gómez, Oliver and Gallego, Alejandro and Pertejo-Fernández, Ana and Sánchez-Cabrero, Darío and Feliu, Jaime and Rodríguez-Salas, Nuria},\n\tmonth = jan,\n\tyear = {2024},\n\tnote = {Number: 2\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {DDM, MUTYH, breast cancer, hereditary, polyposis},\n\tpages = {315},\n}\n\n

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\n \n\n \n \n \n \n \n \n CAD204520 Targets NOTCH1 PEST Domain Mutations in Lymphoproliferative Disorders.\n \n \n \n \n\n\n \n Pagliaro, L.; Cerretani, E.; Vento, F.; Montanaro, A.; Moron Dalla Tor, L.; Simoncini, E.; Giaimo, M.; Gherli, A.; Zamponi, R.; Tartaglione, I.; Lorusso, B.; Scita, M.; Russo, F.; Sammarelli, G.; Todaro, G.; Silini, E. M.; Rigolin, G. M.; Quaini, F.; Cuneo, A.; and Roti, G.\n\n\n \n\n\n\n International Journal of Molecular Sciences, 25(2): 766. January 2024.\n Number: 2 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"CAD204520$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{pagliaro_cad204520_2024,\n\ttitle = {{CAD204520} {Targets} {NOTCH1} {PEST} {Domain} {Mutations} in {Lymphoproliferative} {Disorders}},\n\tvolume = {25},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {1422-0067},\n\turl = {https://www.mdpi.com/1422-0067/25/2/766},\n\tdoi = {10.3390/ijms25020766},\n\tabstract = {NOTCH1 PEST domain mutations are often seen in hematopoietic malignancies, including T-cell acute lymphoblastic leukemia (T-ALL), chronic lymphocytic leukemia (CLL), splenic marginal zone lymphoma (SMZL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL). These mutations play a key role in the development and progression of lymphoproliferative tumors by increasing the Notch signaling and, consequently, promoting cell proliferation, survival, migration, and suppressing apoptosis. There is currently no specific treatment available for cancers caused by NOTCH1 PEST domain mutations. However, several NOTCH1 inhibitors are in development. Among these, inhibition of the Sarco-endoplasmic Ca2+-ATPase (SERCA) showed a greater effect in NOTCH1-mutated tumors compared to the wild-type ones. One example is CAD204520, a benzimidazole derivative active in T-ALL cells harboring NOTCH1 mutations. In this study, we preclinically assessed the effect of CAD204520 in CLL and MCL models and showed that NOTCH1 PEST domain mutations sensitize cells to the anti-leukemic activity mediated by CAD204520. Additionally, we tested the potential of CAD204520 in combination with the current first-line treatment of CLL, venetoclax, and ibrutinib. CAD204520 enhanced the synergistic effect of this treatment regimen only in samples harboring the NOTCH1 PEST domain mutations, thus supporting a role for Notch inhibition in these tumors. In summary, our work provides strong support for the development of CAD204520 as a novel therapeutic approach also in chronic lymphoproliferative disorders carrying NOTCH1 PEST domain mutations, emerging as a promising molecule for combination treatment in this aggressive subset of patients.},\n\tlanguage = {en},\n\tnumber = {2},\n\turldate = {2024-01-24},\n\tjournal = {International Journal of Molecular Sciences},\n\tauthor = {Pagliaro, Luca and Cerretani, Elisa and Vento, Federica and Montanaro, Anna and Moron Dalla Tor, Lucas and Simoncini, Elisa and Giaimo, Mariateresa and Gherli, Andrea and Zamponi, Raffaella and Tartaglione, Isotta and Lorusso, Bruno and Scita, Matteo and Russo, Filomena and Sammarelli, Gabriella and Todaro, Giannalisa and Silini, Enrico Maria and Rigolin, Gian Matteo and Quaini, Federico and Cuneo, Antonio and Roti, Giovanni},\n\tmonth = jan,\n\tyear = {2024},\n\tnote = {Number: 2\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {DDM, LYS, Lymphoma solution, NOTCH1, NOTCH1 PEST domain mutations, chronic lymphocytic leukemia, lymphoproliferative disorders, mantle cell lymphoma, synergy treatment, target therapy},\n\tpages = {766},\n}\n\n

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\n \n\n \n \n \n \n \n \n The Pivotal Role of Whole Genome and Transcriptome Sequencing in a Rare Case of Systemic Mastocytosis with Associated Myelodysplastic/Myeloproliferative Neoplasm with Neutrophilia.\n \n \n \n \n\n\n \n Strasser, B.; Hörmann, G.; and Haushofer, A.\n\n\n \n\n\n\n Clinical Chemistry, 70(1): 350–352. January 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"The$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{strasser_pivotal_2024,\n\ttitle = {The {Pivotal} {Role} of {Whole} {Genome} and {Transcriptome} {Sequencing} in a {Rare} {Case} of {Systemic} {Mastocytosis} with {Associated} {Myelodysplastic}/{Myeloproliferative} {Neoplasm} with {Neutrophilia}},\n\tvolume = {70},\n\tissn = {0009-9147},\n\turl = {https://doi.org/10.1093/clinchem/hvad130},\n\tdoi = {10.1093/clinchem/hvad130},\n\tnumber = {1},\n\turldate = {2024-01-24},\n\tjournal = {Clinical Chemistry},\n\tauthor = {Strasser, Bernhard and Hörmann, Gregor and Haushofer, Alexander},\n\tmonth = jan,\n\tyear = {2024},\n\tkeywords = {Custom, Custom Panel, DDM, Myeloid},\n\tpages = {350--352},\n}\n\n

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\n \n\n \n \n \n \n \n \n Decoding complex inherited phenotypes in rare disorders: the DECIPHERD initiative for rare undiagnosed diseases in Chile.\n \n \n \n \n\n\n \n Poli, M. C.; Rebolledo-Jaramillo, B.; Lagos, C.; Orellana, J.; Moreno, G.; Martín, L. M.; Encina, G.; Böhme, D.; Faundes, V.; Zavala, M. J.; Hasbún, T.; Fischer, S.; Brito, F.; Araya, D.; Lira, M.; de la Cruz, J.; Astudillo, C.; Lay-Son, G.; Cares, C.; Aracena, M.; Martin, E. S.; Coban-Akdemir, Z.; Posey, J. E.; Lupski, J. R.; and Repetto, G. M.\n\n\n \n\n\n\n European Journal of Human Genetics,1–11. January 2024.\n Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"Decoding$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{poli_decoding_2024,\n\ttitle = {Decoding complex inherited phenotypes in rare disorders: the {DECIPHERD} initiative for rare undiagnosed diseases in {Chile}},\n\tcopyright = {2024 The Author(s)},\n\tissn = {1476-5438},\n\tshorttitle = {Decoding complex inherited phenotypes in rare disorders},\n\turl = {https://www.nature.com/articles/s41431-023-01523-5},\n\tdoi = {10.1038/s41431-023-01523-5},\n\tabstract = {Rare diseases affect millions of people worldwide, and most have a genetic etiology. The incorporation of next-generation sequencing into clinical settings, particularly exome and genome sequencing, has resulted in an unprecedented improvement in diagnosis and discovery in the past decade. Nevertheless, these tools are unavailable in many countries, increasing health care gaps between high- and low-and-middle-income countries and prolonging the “diagnostic odyssey” for patients. To advance genomic diagnoses in a setting of limited genomic resources, we developed DECIPHERD, an undiagnosed diseases program in Chile. DECIPHERD was implemented in two phases: training and local development. The training phase relied on international collaboration with Baylor College of Medicine, and the local development was structured as a hybrid model, where clinical and bioinformatics analysis were performed in-house and sequencing outsourced abroad, due to lack of high-throughput equipment in Chile. We describe the implementation process and findings of the first 103 patients. They had heterogeneous phenotypes, including congenital anomalies, intellectual disabilities and/or immune system dysfunction. Patients underwent clinical exome or research exome sequencing, as solo cases or with parents using a trio design. We identified pathogenic, likely pathogenic or variants of unknown significance in genes related to the patients´ phenotypes in 47 (45.6\\%) of them. Half were de novo informative variants, and half of the identified variants have not been previously reported in public databases. DECIPHERD ended the diagnostic odyssey for many participants. This hybrid strategy may be useful for settings of similarly limited genomic resources and lead to discoveries in understudied populations.},\n\tlanguage = {en},\n\turldate = {2024-01-24},\n\tjournal = {European Journal of Human Genetics},\n\tauthor = {Poli, M. Cecilia and Rebolledo-Jaramillo, Boris and Lagos, Catalina and Orellana, Joan and Moreno, Gabriela and Martín, Luz M. and Encina, Gonzalo and Böhme, Daniela and Faundes, Víctor and Zavala, M. Jesús and Hasbún, Trinidad and Fischer, Sara and Brito, Florencia and Araya, Diego and Lira, Manuel and de la Cruz, Javiera and Astudillo, Camila and Lay-Son, Guillermo and Cares, Carolina and Aracena, Mariana and Martin, Esteban San and Coban-Akdemir, Zeynep and Posey, Jennifer E. and Lupski, James R. and Repetto, Gabriela M.},\n\tmonth = jan,\n\tyear = {2024},\n\tnote = {Publisher: Nature Publishing Group},\n\tkeywords = {CES, Clinical Exome Solution, DDM, Disease genetics, Genetics research, Medical genomics, clinical exome sequencing (CES)},\n\tpages = {1--11},\n}\n\n

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\n \n\n \n \n \n \n \n \n TIROSEC: Molecular, Clinical and Histopathological Profile of Papillary Thyroid Carcinoma in a Colombian Cohort.\n \n \n \n \n\n\n \n Cruz-Romero, S. D.; González, S.; Juez, J. Y.; Becerra, D. S.; Baldión, A. M.; Hakim, J. A.; González-Devia, D.; Perdomo, S.; and Rodríguez-Urrego, P. A.\n\n\n \n\n\n\n Advances in Therapy. January 2024.\n \n\n\n\n
\n\n\n\n \n \n $\"TIROSEC:$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{cruz-romero_tirosec_2024,\n\ttitle = {{TIROSEC}: {Molecular}, {Clinical} and {Histopathological} {Profile} of {Papillary} {Thyroid} {Carcinoma} in a {Colombian} {Cohort}},\n\tissn = {1865-8652},\n\tshorttitle = {{TIROSEC}},\n\turl = {https://doi.org/10.1007/s12325-023-02756-y},\n\tdoi = {10.1007/s12325-023-02756-y},\n\tabstract = {In Colombia, thyroid cancer ranks among the highest incidences, yet our population lacks studies on its molecular profile. This study aims to characterize clinical, histopathologic and molecular data in a Colombian cohort with papillary thyroid carcinoma (PTC).},\n\tlanguage = {en},\n\turldate = {2024-01-24},\n\tjournal = {Advances in Therapy},\n\tauthor = {Cruz-Romero, Sergio D. and González, Sebastián and Juez, José Y. and Becerra, David S. and Baldión, Ana M. and Hakim, José A. and González-Devia, Deyanira and Perdomo, Sandra and Rodríguez-Urrego, Paula A.},\n\tmonth = jan,\n\tyear = {2024},\n\tkeywords = {DDM, Insertion-deletion mutation, Molecular sequence data, Neoplasms, Papillary thyroid cancer pathology, Point mutation, STS, Solid Tumor Solution},\n}\n\n

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\n \n 2023\n \n \n (156)\n \n \n

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\n \n\n \n \n \n \n \n \n Functional and clinical characterization of a novel homozygous KCNH2 missense variant in the pore region of Kv11.1 leading to a viable but severe long-QT syndrome.\n \n \n \n \n\n\n \n Delinière, A.; Jaupart, L.; Janin, A.; Millat, G.; Boulin, T.; Andrini, O.; and Chevalier, P.\n\n\n \n\n\n\n Gene, 897: 148076. December 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Functional$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{deliniere_functional_2023,\n\ttitle = {Functional and clinical characterization of a novel homozygous {KCNH2} missense variant in the pore region of {Kv11}.1 leading to a viable but severe long-{QT} syndrome},\n\tvolume = {897},\n\tissn = {0378-1119},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0378111923009174},\n\tdoi = {10.1016/j.gene.2023.148076},\n\tabstract = {Background\nAmong KCNH2 missense loss of function (LOF) variants, homozygosity –at any position in the Kv11.1/hERG channel – is very rare and generally leads to intrauterine death, while heterozygous variants in the pore are responsible for severe Type 2 long-QT syndrome (LQTS). We report a novel homozygous p.Gly603Ser missense variant in the pore of Kv11.1/hERG (KCNH2 c.1807G {\\textgreater} A) discovered in the context of a severe LQTS.\nMethods\nWe carried out a phenotypic family study combined with a functional analysis of mutated and wild-type (WT) Kv11.1 by two-electrode voltage-clamp using the Xenopus laevis oocyte heterologous expression system.\nResults\nThe variant resulted in a severe LQTS phenotype (very prolonged corrected QT interval, T-wave alternans, multiple Torsades de pointes) with a delayed clinical expression in later childhood in the homozygous state, and in a Type 2 LQTS phenotype in the heterozygous state. Expression of KCNH2 p.Gly603Ser cRNA alone elicited detectable current in Xenopus oocytes. Inactivation kinetics and voltage dependence of activation were not significantly affected by the variant. The macroscopic slope conductance of the variant was three-fold less compared to the WT (18.5 ± 9.01 vs 54.7 ± 17.2 μS, p {\\textless} 0.001).\nConclusions\nWe characterized the novel p.Gly603Ser KCNH2 missense LOF variant in the pore region of Kv11.1/hERG leading to a severe but viable LQTS in the homozygous state and an attenuated Type 2 LQTS in heterozygous carriers. To our knowledge we provide the first description of a homozygous variant in the pore-forming region of Kv11.1 with a functional impact but a delayed clinical expression.},\n\turldate = {2024-01-25},\n\tjournal = {Gene},\n\tauthor = {Delinière, Antoine and Jaupart, Laureen and Janin, Alexandre and Millat, Gilles and Boulin, Thomas and Andrini, Olga and Chevalier, Philippe},\n\tmonth = dec,\n\tyear = {2023},\n\tkeywords = {Channelopathy, Custom, Custom Panel, G603S, Kv11.1, Sudden cardiac death, hERG, long-QT syndrome, p.Gly603Ser},\n\tpages = {148076},\n}\n\n

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\n \n\n \n \n \n \n \n \n Molecular Profile of Subungual Melanoma: A MelaNostrum Consortium Study of 68 Cases Reporting BRAF, NRAS, KIT, and TERT Promoter Status.\n \n \n \n \n\n\n \n Millan-Esteban, D.; García-Casado, Z.; Macià, A.; de la Rosa, I.; Torrecilla-Vall-llossera, C.; Penin, R. M.; Manrique - Silva, E.; Pellegrini, S.; Biasin, M. R.; Rizzolo, P.; Gavillero, A.; Di Stefani, A.; Pellegrini, C.; Requena, C.; Fargnoli, M. C.; Peris, K.; Cota, C.; Menin, C.; Landi, M. T.; and Nagore, E.\n\n\n \n\n\n\n Dermatology,1–6. November 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Molecular$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{millan-esteban_molecular_2023,\n\ttitle = {Molecular {Profile} of {Subungual} {Melanoma}: {A} {MelaNostrum} {Consortium} {Study} of 68 {Cases} {Reporting} {BRAF}, {NRAS}, {KIT}, and {TERT} {Promoter} {Status}},\n\tissn = {1018-8665},\n\tshorttitle = {Molecular {Profile} of {Subungual} {Melanoma}},\n\turl = {https://doi.org/10.1159/000534955},\n\tdoi = {10.1159/000534955},\n\tabstract = {Background: Subungual melanoma (SM) is an unusual type of melanocytic tumor affecting the nail apparatus. The mutational prevalence of the most prominently mutated genes in melanoma has been reported in small cohorts of SM, with unclear conclusions on whether SM is different from the rest of melanomas arising in acral locations or not. Hence, the molecular profile of a large series of SM is yet to be described. Objectives: The aim of this study was to describe the molecular characteristics of a large series of SM and their association with demographic and histopathological features. Methods: Patients diagnosed with SM between 2001 and 2021 were identified from six Spanish and Italian healthcare centers. The mutational status for BRAF, NRAS, KIT, and the promoter region of TERT (TERTp) were determined either by Sanger sequencing or next-generation sequencing. Clinical data were retrieved from the hospital databases to elucidate potential associations. Results: A total of 68 SM cases were included. Mutations were most common in BRAF (10.3\\%) and KIT (10\\%), followed by NRAS (7.6\\%), and TERTp (3.8\\%). Their prevalence was similar to that of non-subungual acral melanoma but higher in SM located on the hand than on the foot. Conclusions: To date, this study represents the largest cohort of SM patients with data on the known driver gene mutations. The low mutation rate supports a different etiopathogenic mechanism for SM in comparison of non-acral cutaneous melanoma, particularly for SM of the foot.},\n\turldate = {2024-01-25},\n\tjournal = {Dermatology},\n\tauthor = {Millan-Esteban, David and García-Casado, Zaida and Macià, Anna and de la Rosa, Inés and Torrecilla-Vall-llossera, Clara and Penin, Rosa Maria and Manrique - Silva, Esperanza and Pellegrini, Stefania and Biasin, Maria Raffaella and Rizzolo, Piera and Gavillero, Alicia and Di Stefani, Alessandro and Pellegrini, Cristina and Requena, Celia and Fargnoli, Maria Concetta and Peris, Ketty and Cota, Carlo and Menin, Chiara and Landi, Maria Teresa and Nagore, Eduardo},\n\tmonth = nov,\n\tyear = {2023},\n\tkeywords = {BRAF, KIT, Melanoma, NRAS, STS, Solid Tumor Solution, TERT promoter},\n\tpages = {1--6},\n}\n\n

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\n \n\n \n \n \n \n \n \n An overview of RB1 transcript alterations detected during retinoblastoma genetic screening.\n \n \n \n \n\n\n \n Price, E. A.; Sagoo, M. S.; Reddy, M. A.; and Onadim, Z.\n\n\n \n\n\n\n Ophthalmic Genetics, 0(0): 1–11. November 2023.\n Publisher: Taylor & Francis _eprint: https://doi.org/10.1080/13816810.2023.2270570\n\n\n\n
\n\n\n\n \n \n $\"An$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{price_overview_2023,\n\ttitle = {An overview of {RB1} transcript alterations detected during retinoblastoma genetic screening},\n\tvolume = {0},\n\tissn = {1381-6810},\n\turl = {https://doi.org/10.1080/13816810.2023.2270570},\n\tdoi = {10.1080/13816810.2023.2270570},\n\tabstract = {Identification of pathogenic RB1 variants aids in the clinical management of families with retinoblastoma. We routinely screen DNA for RB1 variants, but transcript analysis can also be used for variant screening, and to help decide variant pathogenicity. DNA was screened by conformation analysis followed by Sanger sequencing. Large deletion/insertions were detected by polymorphism analysis, MLPA and quantitative-PCR. Methylation-specific PCR was used to detect hypermethylation. RNA screening was performed when a DNA pathogenic variant was missing, or to determine effects on splicing. Two hundred and thirteen small coding variants were predicted to affect splicing in 207 patients. Splice donor (sd) variants were nearly twice as frequent as splice acceptor (sa) with the most affected positions being sd + 1 and sa−1. Some missense and nonsense codons altered splicing, while some splice consensus variants did not. Large deletion/insertions can disrupt splicing, but RNA analysis showed that some of these are more complex than indicated by DNA testing. RNA screening found pathogenic variants in 53.8\\% of samples where DNA analysis did not. RB1 splicing is altered by changes at consensus splice sites, some missense and nonsense codons, deep intronic changes and large deletion/insertions. Common alternatively spliced transcripts may complicate analysis. An effective molecular screening strategy would include RNA analysis to help determine pathogenicity.},\n\tnumber = {0},\n\turldate = {2024-01-25},\n\tjournal = {Ophthalmic Genetics},\n\tauthor = {Price, Elizabeth A. and Sagoo, Mandeep S. and Reddy, M. Ashwin and Onadim, Zerrin},\n\tmonth = nov,\n\tyear = {2023},\n\tpmid = {37932244},\n\tnote = {Publisher: Taylor \\& Francis\n\\_eprint: https://doi.org/10.1080/13816810.2023.2270570},\n\tkeywords = {Alamut Visual, RB1, Retinoblastoma, genetic, pathogenic, splicing, transcript},\n\tpages = {1--11},\n}\n\n

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\n \n\n \n \n \n \n \n \n PRAME expression in 137 primary cutaneous melanomas and comparison with 38 related metastases.\n \n \n \n \n\n\n \n Lo Bello, G.; Pini, G. M.; Giagnacovo, M.; and Patriarca, C.\n\n\n \n\n\n\n Pathology - Research and Practice, 251: 154915. November 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"PRAME$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{lo_bello_prame_2023,\n\ttitle = {{PRAME} expression in 137 primary cutaneous melanomas and comparison with 38 related metastases},\n\tvolume = {251},\n\tissn = {0344-0338},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0344033823006167},\n\tdoi = {10.1016/j.prp.2023.154915},\n\tabstract = {Melanocytic lesions have always represented a diagnostic challenge for surgical pathologists. According to the literature, PRAME showed great promise as an immunohistochemical tool in the distinction between benign and malignant melanocytic lesions. In the present study, we retrospectively analyzed 137 thicker (Breslow {\\textgreater} 1 mm) primary cutaneous melanomas with the aim to better understand the utility of PRAME immunohistochemistry in daily practice and also to investigate if PRAME could represent a prognostic biomarker for cutaneous melanomas. PRAME immunohistochemistry was performed in all melanomas and in the metastases with antibodies to PRAME (dilution 1:1000, clone Ab219650) on an automated immunostainer (Ventana Benchmark Ultra) using a brown chromogen (DAB). We found that melanomas (59.1\\%) show diffuse PRAME expression (score 4 +). 99 (72.3\\%) primary cutaneous melanoma had no relapse during the follow-up. Of this group of melanomas, 61/99 (61.6\\%) were diffusely positive for PRAME. 38 (27.7\\%) primary cutaneous melanoma had relapses. Of this group, 28/36 (77.7\\%) were diffusely positive. We did not find any statistical correlation between diffuse PRAME expression and the presence of driver mutation in BRAF gene (p = 0.927), NRAS gene (p = 0.496) or either of the two (p = 0.138). We did not find a prognostic significance of diffuse PRAME expression for relapse (p = 0.462) or survival rate (p = 0.245). The prognostic value of PRAME has been only reported in mucosal, uveal and cutaneous thin melanomas. Here, we show statistical analyses on PRAME expression for melanoma with Breslow {\\textgreater} 1 mm based on survival rate and long-term follow-up. According to our results, PRAME is a useful immunohistochemical ancillary tool in daily practice diagnosis of melanocytic lesions.},\n\turldate = {2024-01-25},\n\tjournal = {Pathology - Research and Practice},\n\tauthor = {Lo Bello, Giuseppe and Pini, Giacomo Maria and Giagnacovo, Marzia and Patriarca, Carlo},\n\tmonth = nov,\n\tyear = {2023},\n\tkeywords = {DDM, Immunohistochemistry, Melanoma, PRAME},\n\tpages = {154915},\n}\n\n

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\n \n\n \n \n \n \n \n \n Long-term follow-up of severe autosomal recessive SP7-related bone disorder.\n \n \n \n \n\n\n \n Gauthier, L. W.; Fontanges, E.; Chapurlat, R.; Collet, C.; and Rossi, M.\n\n\n \n\n\n\n Bone, 179: 116953. October 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Long-term$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{gauthier_long-term_2023,\n\ttitle = {Long-term follow-up of severe autosomal recessive {SP7}-related bone disorder},\n\tvolume = {179},\n\tissn = {8756-3282},\n\turl = {https://www.sciencedirect.com/science/article/pii/S8756328223002867},\n\tdoi = {10.1016/j.bone.2023.116953},\n\tabstract = {The SP7 gene encodes a zinc finger transcription factor (Osterix), which is a member of the Sp subfamily of sequence-specific DNA-binding proteins, playing an important role in osteoblast differentiation and maturation. SP7 pathogenic variants have been described in association with different allelic disorders. Monoallelic or biallelic SP7 variants cause Osteogenesis imperfecta type XII (OI12), a very rare condition characterized by recurrent fractures, skeletal deformities, undertubulation of long bones, hearing loss, no dentinogenesis imperfecta, and white sclerae. Monoallelic or biallelic SP7 variants may also cause sclerotic skeletal dysplasias (SSD), partially overlapping with Juvenile Paget's disease and craniodiaphyseal dysplasia, characterized by skull hyperostosis, long bones sclerosis, large ribs and clavicles, and possible recurrent fractures. Here, we report the long-term follow-up of an 85-year-old woman presenting with a complex bone disorder including features of either OI12 (bone fragility with multiple fractures, severe deformities and short stature) or SSD (striking skull hyperostosis with optic atrophy, very large ribs and clavicles and long bones sclerosis). Exome sequencing showed previously undescribed biallelic loss of function variants in the SP7 gene: NM\\_001173467.2(SP7): c.359\\_362del, p.(Asp120Valfs*11); NM\\_001173467.2(SP7): c.1163\\_1174delinsT, p.(Pro388Leufs*33). RT-qPCR confirmed a severely reduced SP7 transcription compared to controls. Our report provides new insights into the clinical and molecular features and long-term outcome of SP7-related bone disorders (SP7-BD), suggesting a continuum phenotypic spectrum characterized by bone fragility, undertubulation of long bones, scoliosis, and very heterogeneous bone mineral density ranging from osteoporosis to osteosclerosis.},\n\turldate = {2024-01-25},\n\tjournal = {Bone},\n\tauthor = {Gauthier, Lucas W. and Fontanges, Elisabeth and Chapurlat, Roland and Collet, Corinne and Rossi, Massimiliano},\n\tmonth = oct,\n\tyear = {2023},\n\tkeywords = {Alamut, Craniodiaphyseal dysplasia, Fractures, OI12, Osteogenesis imperfecta type XII, Osterix, SP7-related bone disorder, Sclerotic skeletal dysplasia},\n\tpages = {116953},\n}\n\n

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\n \n\n \n \n \n \n \n \n Rare de novo gain-of-function missense variants in DOT1L are associated with developmental delay and congenital anomalies.\n \n \n \n \n\n\n \n Nil, Z.; Deshwar, A. R.; Huang, Y.; Barish, S.; Zhang, X.; Choufani, S.; Le Quesne Stabej, P.; Hayes, I.; Yap, P.; Haldeman-Englert, C.; Wilson, C.; Prescott, T.; Tveten, K.; Vøllo, A.; Haynes, D.; Wheeler, P. G.; Zon, J.; Cytrynbaum, C.; Jobling, R.; Blyth, M.; Banka, S.; Afenjar, A.; Mignot, C.; Robin-Renaldo, F.; Keren, B.; Kanca, O.; Mao, X.; Wegner, D. J.; Sisco, K.; Shinawi, M.; Wangler, M. F.; Weksberg, R.; Yamamoto, S.; Costain, G.; and Bellen, H. J.\n\n\n \n\n\n\n The American Journal of Human Genetics, 110(11): 1919–1937. November 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Rare$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{nil_rare_2023,\n\ttitle = {Rare de novo gain-of-function missense variants in {DOT1L} are associated with developmental delay and congenital anomalies},\n\tvolume = {110},\n\tissn = {0002-9297},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0002929723003221},\n\tdoi = {10.1016/j.ajhg.2023.09.009},\n\tabstract = {Misregulation of histone lysine methylation is associated with several human cancers and with human developmental disorders. DOT1L is an evolutionarily conserved gene encoding a lysine methyltransferase (KMT) that methylates histone 3 lysine-79 (H3K79) and was not previously associated with a Mendelian disease in OMIM. We have identified nine unrelated individuals with seven different de novo heterozygous missense variants in DOT1L through the Undiagnosed Disease Network (UDN), the SickKids Complex Care genomics project, and GeneMatcher. All probands had some degree of global developmental delay/intellectual disability, and most had one or more major congenital anomalies. To assess the pathogenicity of the DOT1L variants, functional studies were performed in Drosophila and human cells. The fruit fly DOT1L ortholog, grappa, is expressed in most cells including neurons in the central nervous system. The identified DOT1L variants behave as gain-of-function alleles in flies and lead to increased H3K79 methylation levels in flies and human cells. Our results show that human DOT1L and fly grappa are required for proper development and that de novo heterozygous variants in DOT1L are associated with a Mendelian disease.},\n\tnumber = {11},\n\turldate = {2024-01-25},\n\tjournal = {The American Journal of Human Genetics},\n\tauthor = {Nil, Zelha and Deshwar, Ashish R. and Huang, Yan and Barish, Scott and Zhang, Xi and Choufani, Sanaa and Le Quesne Stabej, Polona and Hayes, Ian and Yap, Patrick and Haldeman-Englert, Chad and Wilson, Carolyn and Prescott, Trine and Tveten, Kristian and Vøllo, Arve and Haynes, Devon and Wheeler, Patricia G. and Zon, Jessica and Cytrynbaum, Cheryl and Jobling, Rebekah and Blyth, Moira and Banka, Siddharth and Afenjar, Alexandra and Mignot, Cyril and Robin-Renaldo, Florence and Keren, Boris and Kanca, Oguz and Mao, Xiao and Wegner, Daniel J. and Sisco, Kathleen and Shinawi, Marwan and Wangler, Michael F. and Weksberg, Rosanna and Yamamoto, Shinya and Costain, Gregory and Bellen, Hugo J.},\n\tmonth = nov,\n\tyear = {2023},\n\tkeywords = {Alamut, DOT1 Like histone lysine methyltransferase, DOT1L, H3K79 methylation, congenital anomalies, developmental delay, gain of function, gpp, grappa, histone lysine methyltransferase},\n\tpages = {1919--1937},\n}\n\n

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\n \n\n \n \n \n \n \n \n Expanding the Phenotypic and Genotypic Spectrum of Weaver Syndrome: A Missense Variant of the EZH2 Gene.\n \n \n \n \n\n\n \n Kendir-Demirkol, Y.; Yeter, B.; and Jenny, L. A.\n\n\n \n\n\n\n Molecular Syndromology,1–6. September 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Expanding$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{kendir-demirkol_expanding_2023,\n\ttitle = {Expanding the {Phenotypic} and {Genotypic} {Spectrum} of {Weaver} {Syndrome}: {A} {Missense} {Variant} of the {EZH2} {Gene}},\n\tissn = {1661-8769},\n\tshorttitle = {Expanding the {Phenotypic} and {Genotypic} {Spectrum} of {Weaver} {Syndrome}},\n\turl = {https://doi.org/10.1159/000533733},\n\tdoi = {10.1159/000533733},\n\tabstract = {Introduction: Weaver syndrome (WS) is a rare autosomal dominant disorder characterized by distinctive facial features, pre- and post-natal overgrowth, macrocephaly, and variable developmental delay. The characteristic facial features are ocular hypertelorism, a broad forehead, almond-shaped palpebral fissures and, in early childhood, large, fleshy ears, a pointed “stuck-on” chin with horizontal skin creases, and retrognathia. Heterozygous pathogenic/likely pathogenic variants in the enhancer of zeste homolog 2 (EZH2) gene are responsible for WS. Case Presentation: Here, we report a male patient with a heterozygous likely pathogenic variant in EZH2 gene who has tall stature, distinctive facial features, mild development delay, hypoxic-ischemic encephalopathy with a MRI finding of periventricular leukomalacia, gingival hypertrophy, and early onset high hypermetropia. Conclusion: This case demonstrates the importance of reporting detailed molecular and clinical findings in patients to expand the genotypic and phenotypic findings of this rare syndrome.},\n\turldate = {2024-01-25},\n\tjournal = {Molecular Syndromology},\n\tauthor = {Kendir-Demirkol, Yasemin and Yeter, Burcu and Jenny, Laura A.},\n\tmonth = sep,\n\tyear = {2023},\n\tkeywords = {CES, Clinical Exome Solution, DDM, EZH2, Hypermetropia, Leukaemia, Overgrowth, Periventricular leukomalacia, Weaver syndrome, clinical exome sequencing},\n\tpages = {1--6},\n}\n\n

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\n \n\n \n \n \n \n \n Distinct clinico-molecular arterial and venous thrombosis scores for myeloproliferative neoplasms risk stratification.\n \n \n \n\n\n \n Pasquer, H.; Daltro de Oliveira, R.; Vasseur, L.; Soret-Dulphy, J.; Maslah, N.; Zhao, L.; Marcault, C.; Cazaux, M.; Gauthier, N.; Verger, E.; Parquet, N.; Vainchenker, W.; Raffoux, E.; Ugo, V.; Luque Paz, D.; Roy, L.; Lambert, W.; Ianotto, J.; Lippert, E.; Giraudier, S.; Cassinat, B.; Kiladjian, J.; and Benajiba, L.\n\n\n \n\n\n\n Leukemia. December 2023.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{pasquer_distinct_2023,\n\ttitle = {Distinct clinico-molecular arterial and venous thrombosis scores for myeloproliferative neoplasms risk stratification},\n\tissn = {1476-5551},\n\tdoi = {10.1038/s41375-023-02114-5},\n\tabstract = {Current recommended risk scores to predict thrombotic events associated with myeloproliferative neoplasms (MPN) do not discriminate between arterial and venous thrombosis despite their different physiopathology. To define novel stratification systems, we delineated a comprehensive landscape of MPN associated thrombosis across a large long-term follow-up MPN cohort. Prior arterial thrombosis, age {\\textgreater}60 years, cardiovascular risk factors and presence of TET2 or DNMT3A mutations were independently associated with arterial thrombosis in multivariable analysis. ARTS, an ARterial Thrombosis Score, based on these four factors, defined low- (0.37\\% patients-year) and high-risk (1.19\\% patients-year) patients. ARTS performance was superior to the two-tiered conventional risk stratification in our training cohort, across all MPN subtypes, as well as in two external validation cohorts. Prior venous thrombosis and presence of a JAK2V617F mutation with a variant allelic frequency ≥50\\% were independently associated with venous thrombosis. The discrimination potential of VETS, a VEnous Thrombosis Score based on these two factors, was poor, similar to the two-tiered conventional risk stratification. Our study pinpoints arterial and venous thrombosis clinico-molecular differences and proposes an arterial risk score for more accurate patients' stratification. Further improvement of venous risk scores, accounting for additional factors and considering venous thrombosis as a heterogeneous entity is warranted.},\n\tlanguage = {eng},\n\tjournal = {Leukemia},\n\tauthor = {Pasquer, Hélène and Daltro de Oliveira, Rafael and Vasseur, Loic and Soret-Dulphy, Juliette and Maslah, Nabih and Zhao, Lin-Pierre and Marcault, Clémence and Cazaux, Marine and Gauthier, Nicolas and Verger, Emmanuelle and Parquet, Nathalie and Vainchenker, William and Raffoux, Emmanuel and Ugo, Valérie and Luque Paz, Damien and Roy, Lydia and Lambert, Wayne-Corentin and Ianotto, Jean-Christophe and Lippert, Eric and Giraudier, Stéphane and Cassinat, Bruno and Kiladjian, Jean-Jacques and Benajiba, Lina},\n\tmonth = dec,\n\tyear = {2023},\n\tpmid = {38148396},\n\tkeywords = {Custom, Custom MYS, Myeloid},\n}\n\n

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\n \n\n \n \n \n \n \n \n Severe Early-Onset Obesity and Diabetic Ketoacidosis due to a Novel Homozygous c.169C\\textgreaterT p.Arg57* Variant in CEP19 Gene.\n \n \n \n \n\n\n \n Cayir, A.; Turkyilmaz, A.; Rabenstein, H.; Guven, F.; Karagoz, Y. S.; Vuralli, D.; Wabitsch, M.; and Demirbilek, H.\n\n\n \n\n\n\n Molecular Syndromology,1–10. December 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Severe$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{cayir_severe_2023,\n\ttitle = {Severe {Early}-{Onset} {Obesity} and {Diabetic} {Ketoacidosis} due to a {Novel} {Homozygous} c.{169C}{\\textgreater}{T} p.{Arg57}* {Variant} in {CEP19} {Gene}},\n\tissn = {1661-8769},\n\turl = {https://doi.org/10.1159/000535253},\n\tdoi = {10.1159/000535253},\n\tabstract = {Introduction: Early-onset severe obesity is usually the result of an underlying genetic disorder, and several genes have recently been shown to cause syndromic and nonsyndromic forms of obesity. The “centrosomal protein 19 (CEP19)” gene encodes for a centrosomal and ciliary protein. Homozygous variants in the CEP19 gene are extremely rare causes of early-onset severe monogenic obesity. Herein, we present a Turkish family with early-onset severe obesity with variable features. Methods: Sanger sequencing and whole-exome sequencing were performed to identify the genetic etiology in the family. Results: The index case was a 12-year-old female who presented with severe obesity (BMI of 62.7 kg/m2), metabolic syndrome, and diabetic ketoacidosis. Her nonidentical twin female siblings also had early-onset severe obesity, metabolic syndrome, and diabetes. In addition, one of the affected siblings had situs inversus abdominalis, polysplenia, lumbar vertebral fusion, and abnormal lateralization. A novel homozygous nonsense (c.169C\\&gt;T, p. Arg57*) pathogenic variant was detected in exon 3 of the CEP19 gene in all affected members of the family. One unaffected sister and unaffected parents were heterozygous for the variant. This variant is predicted to cause a stop codon at amino acid sequence 57, leading to a truncated CEP19 protein. Discussion/Conclusion: Our study expands the phenotypical manifestations and variation database of CEP19 variants. The findings in one of our patients reaffirm its role in the assembly and function of both motile and immotile cilia.},\n\turldate = {2024-01-23},\n\tjournal = {Molecular Syndromology},\n\tauthor = {Cayir, Atilla and Turkyilmaz, Ayberk and Rabenstein, Hannah and Guven, Fadime and Karagoz, Yuksel Sumeyra and Vuralli, Dogus and Wabitsch, Martin and Demirbilek, Huseyin},\n\tmonth = dec,\n\tyear = {2023},\n\tkeywords = {CEP19, DDM, Diabetic Ketoacidosis, Early-onset Obesity},\n\tpages = {1--10},\n}\n\n

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\n \n\n \n \n \n \n \n Functional and phenotypic consequences of an unusual inversion in MSH2.\n \n \n \n\n\n \n Pelletier, D.; Rath, A.; Sabbaghian, N.; Pelmus, M.; Hudon, C.; Jacob, K.; Witowski, L.; Saskin, A.; Heinen, C. D.; and Foulkes, W. D.\n\n\n \n\n\n\n Familial Cancer. November 2023.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{pelletier_functional_2023,\n\ttitle = {Functional and phenotypic consequences of an unusual inversion in {MSH2}},\n\tissn = {1573-7292},\n\tdoi = {10.1007/s10689-023-00350-3},\n\tabstract = {Lynch syndrome is an autosomal dominant disorder that usually results from a pathogenic germline variant in one of four genes (MSH2, MSH6, MLH1, PMS2) involved in DNA mismatch repair. Carriers of such variants are at risk of developing numerous cancers during adulthood. Here we report on a family suspected of having Lynch syndrome due to a history of endometrial adenocarcinoma, ovarian clear cell carcinoma, and adenocarcinoma of the duodenum in whom we identified a germline 29 nucleotide in-frame inversion in exon 3 of MSH2. We further show that this variant is almost completely absent at the protein level, and that the associated cancers have complete loss of MSH2 and MSH6 expression by immunohistochemistry. Functional investigation of this inversion in a laboratory setting revealed a resultant abnormal protein function. Thus, we have identified an unusual, small germline inversion in a mismatch repair gene that does not lead to a premature stop codon yet appears likely to be causal for the observed cancers.},\n\tlanguage = {eng},\n\tjournal = {Familial Cancer},\n\tauthor = {Pelletier, Dylan and Rath, Abhijit and Sabbaghian, Nelly and Pelmus, Manuela and Hudon, Catherine and Jacob, Karine and Witowski, Leora and Saskin, Avi and Heinen, Christopher D. and Foulkes, William D.},\n\tmonth = nov,\n\tyear = {2023},\n\tpmid = {37957483},\n\tkeywords = {CRISPR/Cas9, DDM, Germline inversion, Lynch syndrome, MSH2, Medical genetics, Mismatch repair},\n}\n\n

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\n \n\n \n \n \n \n \n \n Experience with carnitine palmitoyltransferase II deficiency: diagnostic challenges in the myopathic form.\n \n \n \n \n\n\n \n Yazıcı, H.; Ak, G.; Çelik, M. Y.; Erdem, F.; Yanbolu, A. Y.; Er, E.; Bozacı, A. E.; Güvenç, M. S.; Aykut, A.; Durmaz, A.; Canda, E.; Uçar, S. K.; and Çoker, M.\n\n\n \n\n\n\n Journal of Pediatric Endocrinology and Metabolism, 37(1): 33–41. November 2023.\n Publisher: De Gruyter\n\n\n\n
\n\n\n\n \n \n $\"Experience$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{yazici_experience_2023,\n\ttitle = {Experience with carnitine palmitoyltransferase {II} deficiency: diagnostic challenges in the myopathic form},\n\tvolume = {37},\n\tcopyright = {De Gruyter expressly reserves the right to use all content for commercial text and data mining within the meaning of Section 44b of the German Copyright Act.},\n\tissn = {2191-0251},\n\tshorttitle = {Experience with carnitine palmitoyltransferase {II} deficiency},\n\turl = {https://www.degruyter.com/document/doi/10.1515/jpem-2023-0298/html},\n\tdoi = {10.1515/jpem-2023-0298},\n\tabstract = {Objectives Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive disorder of long-chain fatty acid oxidation. Three clinical phenotypes, lethal neonatal form, severe infantile hepatocardiomuscular form, and myopathic form, have been described in CPT II deficiency. The myopathic form is usually mild and can manifest from infancy to adulthood, characterised by recurrent rhabdomyolysis episodes. The study aimed to investigate the clinical features, biochemical, histopathological, and genetic findings of 13 patients diagnosed with the myopathic form of CPT II deficiency at Ege University Hospital. Methods A retrospective study was conducted with 13 patients with the myopathic form of CPT II deficiency. Our study considered demographic data, triggers of recurrent rhabdomyolysis attacks, biochemical metabolic screening, and molecular analysis. Results Ten patients were examined for rhabdomyolysis of unknown causes. Two patients were diagnosed during family screening, and one was diagnosed during investigations due to increased liver function tests. Acylcarnitine profiles were normal in five patients during rhabdomyolysis. Genetic studies have identified a c.338C\\&gt;T (p.Ser113Leu) variant homozygous in 10 patients. One patient showed a novel frameshift variant compound heterozygous with c.338C\\&gt;T (p.Ser113Leu). Conclusions Plasma acylcarnitine analysis should be preferred as it is superior to DBS acylcarnitine analysis in diagnosing CPT II deficiency. Even if plasma acylcarnitine analysis is impossible, CPT2 gene analysis should be performed. Our study emphasizes that CPT II deficiency should be considered in the differential diagnosis of recurrent rhabdomyolysis, even if typical acylcarnitine elevation does not accompany it.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2024-01-23},\n\tjournal = {Journal of Pediatric Endocrinology and Metabolism},\n\tauthor = {Yazıcı, Havva and Ak, Gunes and Çelik, Merve Yoldas and Erdem, Fehime and Yanbolu, Ayse Yuksel and Er, Esra and Bozacı, Ayse Ergül and Güvenç, Merve Saka and Aykut, Ayca and Durmaz, Asude and Canda, Ebru and Uçar, Sema Kalkan and Çoker, Mahmut},\n\tmonth = nov,\n\tyear = {2023},\n\tnote = {Publisher: De Gruyter},\n\tkeywords = {CES, CES v3, CPT II, Clinical Exome Solution, DDM, acylcarnitines, clinical exome sequencing (CES), fatty acid oxidation disorder, metabolic myopathy, rhabdomyolysis},\n\tpages = {33--41},\n}\n\n

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\n \n\n \n \n \n \n \n \n Resistance to osimertinib in advanced EGFR-mutated NSCLC: a prospective study of molecular genotyping on tissue and liquid biopsies.\n \n \n \n \n\n\n \n Leonetti, A.; Verzè, M.; Minari, R.; Perrone, F.; Gnetti, L.; Bordi, P.; Pluchino, M.; Nizzoli, R.; Azzoni, C.; Bottarelli, L.; Lagrasta, C. a. M.; Mazzaschi, G.; Buti, S.; Gasparro, D.; Cosenza, A.; Ferri, L.; Majori, M.; De Filippo, M.; Ampollini, L.; La Monica, S.; Alfieri, R.; Silini, E. M.; and Tiseo, M.\n\n\n \n\n\n\n British Journal of Cancer, 130(1): 135–142. November 2023.\n Number: 1 Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"Resistance$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{leonetti_resistance_2023,\n\ttitle = {Resistance to osimertinib in advanced {EGFR}-mutated {NSCLC}: a prospective study of molecular genotyping on tissue and liquid biopsies},\n\tvolume = {130},\n\tcopyright = {2023 The Author(s), under exclusive licence to Springer Nature Limited},\n\tissn = {1532-1827},\n\tshorttitle = {Resistance to osimertinib in advanced {EGFR}-mutated {NSCLC}},\n\turl = {https://www.nature.com/articles/s41416-023-02475-9},\n\tdoi = {10.1038/s41416-023-02475-9},\n\tabstract = {Resistance to osimertinib in advanced EGFR-mutated non-small cell lung cancer (NSCLC) constitutes a significant challenge for clinicians either in terms of molecular diagnosis and subsequent therapeutic implications.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2024-01-24},\n\tjournal = {British Journal of Cancer},\n\tauthor = {Leonetti, A. and Verzè, M. and Minari, R. and Perrone, F. and Gnetti, L. and Bordi, P. and Pluchino, M. and Nizzoli, R. and Azzoni, C. and Bottarelli, L. and Lagrasta, C. a. M. and Mazzaschi, G. and Buti, S. and Gasparro, D. and Cosenza, A. and Ferri, L. and Majori, M. and De Filippo, M. and Ampollini, L. and La Monica, S. and Alfieri, R. and Silini, E. M. and Tiseo, M.},\n\tmonth = nov,\n\tyear = {2023},\n\tnote = {Number: 1\nPublisher: Nature Publishing Group},\n\tkeywords = {Cancer genomics, DDM, Molecular medicine, Non-small-cell lung cancer, Oncogenes, STSplus, Solid Tumor Solution Plus},\n\tpages = {135--142},\n}\n\n

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\n \n\n \n \n \n \n \n Soft Tissue Aneurysmal Bone Cyst in the Sartorius Muscle of a 13-Year-Old Boy Mimicking Myositis Ossificans: Case Report.\n \n \n \n\n\n \n Pena-Burgos, E. M.; Serra Del Carpio, G.; Bernabéu, D.; Cordero García, J. M.; Ortiz-Cruz, E. J.; and Pozo-Kreilinger, J. J.\n\n\n \n\n\n\n International Journal of Surgical Pathology,10668969231208030. November 2023.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{pena-burgos_soft_2023,\n\ttitle = {Soft {Tissue} {Aneurysmal} {Bone} {Cyst} in the {Sartorius} {Muscle} of a 13-{Year}-{Old} {Boy} {Mimicking} {Myositis} {Ossificans}: {Case} {Report}},\n\tissn = {1940-2465},\n\tshorttitle = {Soft {Tissue} {Aneurysmal} {Bone} {Cyst} in the {Sartorius} {Muscle} of a 13-{Year}-{Old} {Boy} {Mimicking} {Myositis} {Ossificans}},\n\tdoi = {10.1177/10668969231208030},\n\tabstract = {INTRODUCTION: A soft tissue aneurysmal bone cyst is an extremely rare tumor. The objective of the article is to present the clinical, radiological, and histopathological features of a very unusual neoplasm of soft tissues.\nCASE REPORT: A 13-year-old male patient presented a painful, mobile, and rapidly growing mass on the posteromedial aspect of his left knee. Imaging studies revealed a mass that arose from the medial surface of the distal sartorius muscle, with extension to the subcutaneous fat tissue. It was a well-circumscribed solid tumor with a peripheral rim calcification on plain film, computerized tomography, and ultrasound (zonal phenomenon). On magnetic resonance imaging, a heterogenous mass on T1-weighted images (WI) and T2-WI was seen, with a peripheral hypointense rim in both sequences. An outstanding edema on T2-WI extending to the soft tissue and muscles of the medial compartment of the knee was detected. The mass was resected, and the "tumoral mimickers" histopathological and molecular (next-generation sequencing) diagnoses confirmed a soft tissue aneurysmal bone cyst. A follow-up showed that the patient was free of disease 12 months after surgery.\nCONCLUSION: Soft tissue aneurysmal bone cyst is a rare tumor. Appropriate clinical and radiological correlation should be performed to differentiate it from other tumor mimickers.},\n\tlanguage = {eng},\n\tjournal = {International Journal of Surgical Pathology},\n\tauthor = {Pena-Burgos, Eva Manuela and Serra Del Carpio, Gabriela and Bernabéu, Daniel and Cordero García, Jose Manuel and Ortiz-Cruz, Eduardo Jose and Pozo-Kreilinger, Jose Juan},\n\tmonth = nov,\n\tyear = {2023},\n\tpmid = {37933149},\n\tkeywords = {Custom, Custom Panel, Custom STS, DDM, aneurysmal bone cyst, myositis ossificans, soft tissue aneurysmal bone cyst},\n\tpages = {10668969231208030},\n}\n\n

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\n \n\n \n \n \n \n \n \n A Novel SPAST Variant Associated with Isolated Spastic Paraplegia.\n \n \n \n \n\n\n \n Høyer, H.; Nakken, O.; and Holmøy, T.\n\n\n \n\n\n\n Case Reports in Genetics, 2023: e4553365. December 2023.\n Publisher: Hindawi\n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{hoyer_novel_2023,\n\ttitle = {A {Novel} \\textit{{SPAST}} {Variant} {Associated} with {Isolated} {Spastic} {Paraplegia}},\n\tvolume = {2023},\n\tissn = {2090-6544},\n\turl = {https://www.hindawi.com/journals/crig/2023/4553365/},\n\tdoi = {10.1155/2023/4553365},\n\tabstract = {Genetic variants in SPAST are the most common cause of hereditary spastic paraplegia (HSP), entitled spastic paraplegia type 4 (SPG4). Inheritance is autosomal dominant, and age of onset can vary from childhood to adulthood. Pathogenic SPAST variants are often observed in isolated cases, likely due to reduced penetrance and clinical variability. We report an isolated case of SPG4 associated with a novel likely pathogenic variant in SPAST. A 38-year-old woman presented with an eight-year history of progressive difficulty walking. Neurological examination revealed spastic paraparesis in the absence of upper motor neuron dysfunction, sensory deficits, or intellectual disability. Magnetic resonance imaging (MRI) of the brain and spinal cord was normal. No family members had similar complaints. Genetic analysis revealed a novel heterozygous sequence variant in SPAST, c.1751A {\\textgreater} G p.(Asp584Gly) (NM\\_014946.4). The affected amino acid is highly conserved among orthologue and paralogue species. Four other nucleotide substitutions predicted to affect the same amino acid, a “hot spot”, have been reported previously in adult-onset HSP. This report describes a novel SPAST variant in a female with HSP without a known family history of the disorder.},\n\tlanguage = {en},\n\turldate = {2024-01-24},\n\tjournal = {Case Reports in Genetics},\n\tauthor = {Høyer, Helle and Nakken, Ola and Holmøy, Trygve},\n\tmonth = dec,\n\tyear = {2023},\n\tnote = {Publisher: Hindawi},\n\tkeywords = {Alamut Visual},\n\tpages = {e4553365},\n}\n\n

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\n \n\n \n \n \n \n \n Triple Genetic Diagnosis in a Patient with Late-Onset Leukodystrophy and Mild Intellectual Disability.\n \n \n \n\n\n \n Pasquetti, D.; Gazzellone, A.; Rossi, S.; Orteschi, D.; L'Erario, F. F.; Concolino, P.; Minucci, A.; Dionisi-Vici, C.; Genuardi, M.; Silvestri, G.; and Chiurazzi, P.\n\n\n \n\n\n\n International Journal of Molecular Sciences, 25(1): 495. December 2023.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{pasquetti_triple_2023,\n\ttitle = {Triple {Genetic} {Diagnosis} in a {Patient} with {Late}-{Onset} {Leukodystrophy} and {Mild} {Intellectual} {Disability}},\n\tvolume = {25},\n\tissn = {1422-0067},\n\tdoi = {10.3390/ijms25010495},\n\tabstract = {We describe the complex case of a 44-year-old man with polycystic kidney disease, mild cognitive impairment, and tremors in the upper limbs. Brain MRI showed lesions compatible with leukodystrophy. The diagnostic process, which included clinical exome sequencing (CES) and chromosomal microarray analysis (CMA), revealed a triple diagnosis: autosomal dominant polycystic kidney disease (ADPKD) due to a pathogenic variant, c.2152C{\\textgreater}T-p.(Gln718Ter), in the PKD1 gene; late-onset phenylketonuria due to the presence of two missense variants, c.842C{\\textgreater}T-p.(Pro281Leu) and c.143T{\\textgreater}C-p.(Leu48Ser) in the PAH gene; and a 915 Kb duplication on chromosome 15. Few patients with multiple concurrent genetic diagnoses are reported in the literature; in this ADPKD patient, genome-wide analysis allowed for the diagnosis of adult-onset phenylketonuria (which would have otherwise gone unnoticed) and a 15q11.2 duplication responsible for cognitive and behavioral impairment with incomplete penetrance. This case underlines the importance of clinical genetics for interpreting complex results obtained by genome-wide techniques, and for diagnosing concurrent late-onset monogenic conditions.},\n\tlanguage = {eng},\n\tnumber = {1},\n\tjournal = {International Journal of Molecular Sciences},\n\tauthor = {Pasquetti, Domizia and Gazzellone, Annalisa and Rossi, Salvatore and Orteschi, Daniela and L'Erario, Federica Francesca and Concolino, Paola and Minucci, Angelo and Dionisi-Vici, Carlo and Genuardi, Maurizio and Silvestri, Gabriella and Chiurazzi, Pietro},\n\tmonth = dec,\n\tyear = {2023},\n\tpmid = {38203665},\n\tpmcid = {PMC10778870},\n\tkeywords = {15q11.2 duplication, Adult, CES, CES v2, CMA, Chromosomes, Human, Pair 15, Clinical Exome Solution v2, Cognitive Dysfunction, DDM, Demyelinating Diseases, Humans, Intellectual Disability, Late Onset Disorders, Lipid Metabolism Disorders, Lysosomal Storage Diseases, Male, Neurodegenerative Diseases, Phenylketonurias, Polycystic Kidney, Autosomal Dominant, intellectual disability, leukodystrophy, phenylketonuria, polycystic kidney disease},\n\tpages = {495},\n}\n\n

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\n \n\n \n \n \n \n \n \n Single-Cell DNA Sequencing and Immunophenotypic Profiling to Track Clonal Evolution in an Acute Myeloid Leukemia Patient.\n \n \n \n \n\n\n \n García-Álvarez, M.; Yeguas, A.; Jiménez, C.; Medina-Herrera, A.; González-Calle, V.; Hernández-Ruano, M.; Maldonado, R.; Aires, I.; Casquero, C.; Sánchez-Villares, I.; Balanzategui, A.; Sarasquete, M. E.; Alcoceba, M.; Vidriales, M. B.; González-Díaz, M.; García-Sanz, R.; and Chillón, M. C.\n\n\n \n\n\n\n Biomedicines, 12(1): 66. December 2023.\n Number: 1 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Single-Cell$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{garcia-alvarez_single-cell_2023,\n\ttitle = {Single-{Cell} {DNA} {Sequencing} and {Immunophenotypic} {Profiling} to {Track} {Clonal} {Evolution} in an {Acute} {Myeloid} {Leukemia} {Patient}},\n\tvolume = {12},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2227-9059},\n\turl = {https://www.mdpi.com/2227-9059/12/1/66},\n\tdoi = {10.3390/biomedicines12010066},\n\tabstract = {Single-cell DNA sequencing can address the sequence of somatic genetic events during myeloid transformation in relapsed acute myeloid leukemia (AML). We present an NPM1-mutated AML patient with an initial low ratio of FLT3-ITD (low-risk ELN-2017), treated with midostaurin combined with standard chemotherapy as front-line treatment, and with salvage therapy plus gilteritinib following allogenic stem cell transplantation after relapse. Simultaneous single-cell DNA sequencing and cell-surface immunophenotyping was used in diagnostic and relapse samples to understand the clinical scenario of this patient and to reconstruct the clonal composition of both tumors. Four independent clones were present before treatment: DNMT3A/DNMT3A/NPM1 (63.9\\%), DNMT3A/DNMT3A (13.9\\%), DNMT3A/DNMT3A/NPM1/FLT3 (13.8\\%), as well as a wild-type clone (8.3\\%), but only the minor clone with FLT3-ITD survived and expanded after therapy, being the most represented one (58.6\\%) at relapse. FLT3-ITD was subclonal and was found only in the myeloid blast population (CD38/CD117/CD123). Our study shows the usefulness of this approach to reveal the clonal architecture of the leukemia and the identification of small subclones at diagnosis and relapse that may explain how the neoplastic cells can escape from the activity of different treatments in a stepwise process that impedes the disease cure despite different stages of complete remission.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2024-01-24},\n\tjournal = {Biomedicines},\n\tauthor = {García-Álvarez, María and Yeguas, Ana and Jiménez, Cristina and Medina-Herrera, Alejandro and González-Calle, Verónica and Hernández-Ruano, Montserrat and Maldonado, Rebeca and Aires, Irene and Casquero, Cristina and Sánchez-Villares, Inmaculada and Balanzategui, Ana and Sarasquete, María Eugenia and Alcoceba, Miguel and Vidriales, María Belén and González-Díaz, Marcos and García-Sanz, Ramón and Chillón, María Carmen},\n\tmonth = dec,\n\tyear = {2023},\n\tnote = {Number: 1\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Custom, Custom Pan-Myeloid Panel, Custom Panel, FLT3-ITD, acute myeloid leukemia, gilteritinib and clonal evolution, immunophenotype, midostaurin, next-generation sequencing, single-cell DNA sequencing},\n\tpages = {66},\n}\n\n

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\n \n\n \n \n \n \n \n \n Genotype–Phenotype Relationship among 785 Unrelated White Women with Inherited Congenital Factor VII Deficiency: A Three-Center Database Study.\n \n \n \n \n\n\n \n Halimeh, S.; Koch, L.; Kenet, G.; Kuta, P.; Rahmfeld, T.; Stoll, M.; and Nowak-Göttl, U.\n\n\n \n\n\n\n Journal of Clinical Medicine, 13(1): 49. December 2023.\n Number: 1 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Genotype–Phenotype$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{halimeh_genotypephenotype_2023,\n\ttitle = {Genotype–{Phenotype} {Relationship} among 785 {Unrelated} {White} {Women} with {Inherited} {Congenital} {Factor} {VII} {Deficiency}: {A} {Three}-{Center} {Database} {Study}},\n\tvolume = {13},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2077-0383},\n\tshorttitle = {Genotype–{Phenotype} {Relationship} among 785 {Unrelated} {White} {Women} with {Inherited} {Congenital} {Factor} {VII} {Deficiency}},\n\turl = {https://www.mdpi.com/2077-0383/13/1/49},\n\tdoi = {10.3390/jcm13010049},\n\tabstract = {Background: Congenital factor VII (FVII) deficiency, a rare bleeding disorder resulting from mutations in the F7 gene with autosomal recessive inheritance, exhibits clinical heterogeneity that lacks a strong correlation with FVII:C levels. The objective of this study was to discern genetic defects and assess their associations with the clinical phenotype in a substantial cohort comprising 785 white women exhibiting FVII:C levels below the age-dependent cut-off percentage. Patients and Methods: Individuals with verified inherited factor VII deficiency underwent i) genotyping using the Sanger method and multiplex ligation-dependent probe amplification (MLPA) to identify F7 mutations, including common polymorphic variants. Additionally, they were ii) categorized based on clinical bleeding scores (BS). Thrombophilic variants and blood groups were also determined in the study participants. Results: The probands in this study encompassed both asymptomatic individuals (referred for a laboratory investigation due to recurrent prolonged prothrombin time; n = 221) and patients who manifested mild, moderate, or severe bleeding episodes (n = 564). The spectrum of bleeding symptoms included epistaxis, gum bleeding, gastrointestinal bleeding, hematuria, postoperative bleeding, and gynecologic hemorrhage. The median ISTH bleeding score (BS) recorded within a two-year period prior to the work-up was 2 (0–17). Notably, this score was significantly higher in symptomatic women compared to their asymptomatic counterparts (3 versus 0; p {\\textless} 0.001). The corresponding PBAC score before hormonal treatment stood at 225 (5–1200), exhibiting a positive correlation with the ISTH BS (rho = 0.38; p = 0.001). Blood group O was more prevalent in symptomatic women compared to asymptomatic individuals (58 versus 42\\%; p = 0.01). Among the 329 women (42\\%), known and novel mutations in the F7 gene, encompassing coding regions, exon/intron boundaries, and the promoter region, were identified, while common polymorphisms were detected in 647 subjects (95\\%). Logistic regression analysis, adjusted for clinical and laboratory data (including blood group, FVII activity, the presence of F7 gene mutations and/or polymorphisms, thrombophilia status, and additional factor deficiencies) revealed that older age at referral (increase per year) (odds/95\\% CI: 1.02/1.007–1.03), the presence of blood group O (odds/95\\% CI: 1.9/1.2–3.3), and the coexistence of further bleeding defects (odds/95\\% CI: 1.8/1.03–3.1) partially account for the differences in the clinical bleeding phenotype associated with FVII deficiency. Conclusion: The clinical phenotype in individuals with FVII deficiency is impacted by factors such as age, blood group, and the concurrent presence of other bleeding defects.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2024-01-23},\n\tjournal = {Journal of Clinical Medicine},\n\tauthor = {Halimeh, Susan and Koch, Lydia and Kenet, Gili and Kuta, Piotr and Rahmfeld, Tess and Stoll, Monika and Nowak-Göttl, Ulrike},\n\tmonth = dec,\n\tyear = {2023},\n\tnote = {Number: 1\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Alamut, Alamut Visual v2.15, factor VII deficiency, genotype–phenotype relationship, rare coagulation disorders},\n\tpages = {49},\n}\n\n

\n\n\n

\n Background: Congenital factor VII (FVII) deficiency, a rare bleeding disorder resulting from mutations in the F7 gene with autosomal recessive inheritance, exhibits clinical heterogeneity that lacks a strong correlation with FVII:C levels. The objective of this study was to discern genetic defects and assess their associations with the clinical phenotype in a substantial cohort comprising 785 white women exhibiting FVII:C levels below the age-dependent cut-off percentage. Patients and Methods: Individuals with verified inherited factor VII deficiency underwent i) genotyping using the Sanger method and multiplex ligation-dependent probe amplification (MLPA) to identify F7 mutations, including common polymorphic variants. Additionally, they were ii) categorized based on clinical bleeding scores (BS). Thrombophilic variants and blood groups were also determined in the study participants. Results: The probands in this study encompassed both asymptomatic individuals (referred for a laboratory investigation due to recurrent prolonged prothrombin time; n = 221) and patients who manifested mild, moderate, or severe bleeding episodes (n = 564). The spectrum of bleeding symptoms included epistaxis, gum bleeding, gastrointestinal bleeding, hematuria, postoperative bleeding, and gynecologic hemorrhage. The median ISTH bleeding score (BS) recorded within a two-year period prior to the work-up was 2 (0–17). Notably, this score was significantly higher in symptomatic women compared to their asymptomatic counterparts (3 versus 0; p \\textless 0.001). The corresponding PBAC score before hormonal treatment stood at 225 (5–1200), exhibiting a positive correlation with the ISTH BS (rho = 0.38; p = 0.001). Blood group O was more prevalent in symptomatic women compared to asymptomatic individuals (58 versus 42%; p = 0.01). Among the 329 women (42%), known and novel mutations in the F7 gene, encompassing coding regions, exon/intron boundaries, and the promoter region, were identified, while common polymorphisms were detected in 647 subjects (95%). Logistic regression analysis, adjusted for clinical and laboratory data (including blood group, FVII activity, the presence of F7 gene mutations and/or polymorphisms, thrombophilia status, and additional factor deficiencies) revealed that older age at referral (increase per year) (odds/95% CI: 1.02/1.007–1.03), the presence of blood group O (odds/95% CI: 1.9/1.2–3.3), and the coexistence of further bleeding defects (odds/95% CI: 1.8/1.03–3.1) partially account for the differences in the clinical bleeding phenotype associated with FVII deficiency. Conclusion: The clinical phenotype in individuals with FVII deficiency is impacted by factors such as age, blood group, and the concurrent presence of other bleeding defects.\n

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\n \n\n \n \n \n \n \n \n A NOVEL LOXHD1 PATHOGENIC VARIANT IN GREECE: CASE STUDY OF A DNFB77 NONSYNDROMIC HEARING IMPAIRMENT.\n \n \n \n \n\n\n \n Kalentakis, Z.; and Stamataki, S.\n\n\n \n\n\n\n Journal of Hearing Science, 13(4): 55–59. December 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{kalentakis_novel_2023,\n\ttitle = {A {NOVEL} {LOXHD1} {PATHOGENIC} {VARIANT} {IN} {GREECE}: {CASE} {STUDY} {OF} {A} {DNFB77} {NONSYNDROMIC} {HEARING} {IMPAIRMENT}},\n\tvolume = {13},\n\tissn = {2083-389X, 2084-3127},\n\tshorttitle = {A {NOVEL} {LOXHD1} {PATHOGENIC} {VARIANT} {IN} {GREECE}},\n\turl = {https://www.journalofhearingscience.com/A-NOVEL-LOXHD1-PATHOGENIC-VARIANT-IN-GREECE-CASE-STUDY-OF-A-DNFB77-NONSYNDROMIC-HEARING,175999,0,2.html},\n\tdoi = {10.17430/jhs/175999},\n\tabstract = {Background:  Genetic deficits cause 80\\% of congenital prelingual hearing loss. Some 80\\% of these cases are nonsyndromic and most follow an autosomal recessive pattern of inheritance. More than 80 genes have so far been identified as pathogenic. In this study, we focus on a recently mapped gene,...},\n\tlanguage = {english},\n\tnumber = {4},\n\turldate = {2024-01-23},\n\tjournal = {Journal of Hearing Science},\n\tauthor = {Kalentakis, Zacharias and Stamataki, Sofia},\n\tmonth = dec,\n\tyear = {2023},\n\tkeywords = {CES v2, Clinical Exome Solution v2, DDM, DFNB77, LOXHD1, clinical exome sequencing (CES), genetic hearing loss, nonsyndromic hearing loss},\n\tpages = {55--59},\n}\n\n

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\n \n\n \n \n \n \n \n \n NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy.\n \n \n \n \n\n\n \n Hurtado-Navarro, L.; Cuenca-Zamora, E. J.; Zamora, L.; Bellosillo, B.; Such, E.; Soler-Espejo, E.; Martínez-Banaclocha, H.; Hernández-Rivas, J. M.; Marco-Ayala, J.; Martínez-Alarcón, L.; Linares-Latorre, L.; García-Ávila, S.; Amat-Martínez, P.; González, T.; Arnan, M.; Pomares-Marín, H.; Carreño-Tarragona, G.; Chen-Liang, T. H.; Herranz, M. T.; García-Palenciano, C.; Morales, M. L.; Jerez, A.; Lozano, M. L.; Teruel-Montoya, R.; Pelegrín, P.; and Ferrer-Marín, F.\n\n\n \n\n\n\n Cell Reports Medicine, 4(12). December 2023.\n Publisher: Elsevier\n\n\n\n
\n\n\n\n \n \n $\"NLRP3$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{hurtado-navarro_nlrp3_2023,\n\ttitle = {{NLRP3} inflammasome activation and symptom burden in {KRAS}-mutated {CMML} patients is reverted by {IL}-1 blocking therapy},\n\tvolume = {4},\n\tissn = {2666-3791},\n\turl = {https://www.cell.com/cell-reports-medicine/abstract/S2666-3791(23)00546-3},\n\tdoi = {10.1016/j.xcrm.2023.101329},\n\tlanguage = {English},\n\tnumber = {12},\n\turldate = {2024-01-23},\n\tjournal = {Cell Reports Medicine},\n\tauthor = {Hurtado-Navarro, Laura and Cuenca-Zamora, Ernesto José and Zamora, Lurdes and Bellosillo, Beatriz and Such, Esperanza and Soler-Espejo, Eva and Martínez-Banaclocha, Helios and Hernández-Rivas, Jesús M. and Marco-Ayala, Javier and Martínez-Alarcón, Laura and Linares-Latorre, Lola and García-Ávila, Sara and Amat-Martínez, Paula and González, Teresa and Arnan, Montserrat and Pomares-Marín, Helena and Carreño-Tarragona, Gonzalo and Chen-Liang, Tzu Hua and Herranz, María T. and García-Palenciano, Carlos and Morales, María Luz and Jerez, Andrés and Lozano, María L. and Teruel-Montoya, Raúl and Pelegrín, Pablo and Ferrer-Marín, Francisca},\n\tmonth = dec,\n\tyear = {2023},\n\tpmid = {38118408},\n\tnote = {Publisher: Elsevier},\n\tkeywords = {CMML, IL-1 blockers, KRAS, NLRP3 blockers, NLRP3 inflammasome, RAS mutations, anakinra, inflammation, myelodysplastic syndromes, myeloproliferative neoplasms},\n}\n\n

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\n \n\n \n \n \n \n \n \n ETV6::ABL1-Positive Myeloid Neoplasm: A Case of a Durable Response to Imatinib Mesylate without Additional or Previous Treatment.\n \n \n \n \n\n\n \n Bochicchio, M. T.; Marconi, G.; Baldazzi, C.; Bandini, L.; Ruggieri, F.; Lucchesi, A.; Agostinelli, C.; Sabattini, E.; Orsatti, A.; Ferrari, A.; Capirossi, G.; Servili, C.; Ghelli Luserna di Rorà, A.; Martinelli, G.; Simonetti, G.; and Rosti, G.\n\n\n \n\n\n\n International Journal of Molecular Sciences, 25(1): 118. December 2023.\n Number: 1 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"ETV6::ABL1-Positive$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{bochicchio_etv6abl1-positive_2023,\n\ttitle = {{ETV6}::{ABL1}-{Positive} {Myeloid} {Neoplasm}: {A} {Case} of a {Durable} {Response} to {Imatinib} {Mesylate} without {Additional} or {Previous} {Treatment}},\n\tvolume = {25},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {1422-0067},\n\tshorttitle = {{ETV6}},\n\turl = {https://www.mdpi.com/1422-0067/25/1/118},\n\tdoi = {10.3390/ijms25010118},\n\tabstract = {ETV6::ABL1 rearranged neoplasms are rare hematological diseases. To date, about 80 cases have been reported, including myeloid and lymphoid leukemias. The ETV6 gene codes for an ETS family transcription factor and several fusion partners have been described. When translocated, ETV6 causes the constitutive activation of the partner genes. Here, we report the case of a 54-year-old woman with a cryptic insertion of the 3′ region of ABL1 in the ETV6 gene. The patient was first diagnosed with idiopathic hypereosinophilic syndrome, according to the clinical history, conventional cytogenetics, standard molecular analyses and pathologist description. Next generation sequencing of diagnosis samples unexpectedly detected both ETV6::ABL1 type A and B fusion transcripts, which were then confirmed by FISH. The diagnosis was Myeloid/Lymphoid neoplasm with ETV6::ABL1 fusion, and the patient received imatinib mesylate treatment. In a follow-up after more than one year, the patient still maintained the molecular and complete hematological responses. This case highlights the importance of timely and proper diagnostics and prompt tyrosine kinase inhibitor treatment.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2024-01-23},\n\tjournal = {International Journal of Molecular Sciences},\n\tauthor = {Bochicchio, Maria Teresa and Marconi, Giovanni and Baldazzi, Carmen and Bandini, Lorenza and Ruggieri, Francesca and Lucchesi, Alessandro and Agostinelli, Claudio and Sabattini, Elena and Orsatti, Agnese and Ferrari, Anna and Capirossi, Giorgia and Servili, Chiara and Ghelli Luserna di Rorà, Andrea and Martinelli, Giovanni and Simonetti, Giorgia and Rosti, Gianantonio},\n\tmonth = dec,\n\tyear = {2023},\n\tnote = {Number: 1\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {DDM, ETV6::ABL1, MYS plus, MYS+, Myeloid Plus, diagnostic RNA panels, fusion genes, imatinib mesylate, myeloid/lymphoid neoplasm, next generation sequencing},\n\tpages = {118},\n}\n\n

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\n \n\n \n \n \n \n \n \n Characteristics and clinical behavior of acute myeloid leukemia harboring rare non-A/B/D nucleophosmin (NPM1) gene mutation subtypes: a single-center experience and review of the literature.\n \n \n \n \n\n\n \n Mutti, M.; Cordella, S.; Parisotto, A.; Bettelli, F.; Morselli, M.; Cuoghi, A.; Bresciani, P.; Messerotti, A.; Gilioli, A.; Pioli, V.; Giusti, D.; Colaci, E.; Cassanelli, L.; Paolini, A.; Martinelli, S.; Maffei, R.; Riva, G.; Nasillo, V.; Sarti, M.; Trenti, T.; Comoli, P.; Tagliafico, E.; Manfredini, R.; Eccher, A.; Lagreca, I.; Barozzi, P.; Potenza, L.; Marasca, R.; Candoni, A.; Luppi, M.; and Forghieri, F.\n\n\n \n\n\n\n Leukemia & Lymphoma, 0(0): 1–5. December 2023.\n Publisher: Taylor & Francis _eprint: https://doi.org/10.1080/10428194.2023.2294695\n\n\n\n
\n\n\n\n \n \n $\"Characteristics$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{mutti_characteristics_2023,\n\ttitle = {Characteristics and clinical behavior of acute myeloid leukemia harboring rare non-{A}/{B}/{D} nucleophosmin ({NPM1}) gene mutation subtypes: a single-center experience and review of the literature},\n\tvolume = {0},\n\tissn = {1042-8194},\n\tshorttitle = {Characteristics and clinical behavior of acute myeloid leukemia harboring rare non-{A}/{B}/{D} nucleophosmin ({NPM1}) gene mutation subtypes},\n\turl = {https://doi.org/10.1080/10428194.2023.2294695},\n\tdoi = {10.1080/10428194.2023.2294695},\n\tnumber = {0},\n\turldate = {2024-01-23},\n\tjournal = {Leukemia \\& Lymphoma},\n\tauthor = {Mutti, Martina and Cordella, Stefano and Parisotto, Angelica and Bettelli, Francesca and Morselli, Monica and Cuoghi, Angela and Bresciani, Paola and Messerotti, Andrea and Gilioli, Andrea and Pioli, Valeria and Giusti, Davide and Colaci, Elisabetta and Cassanelli, Luca and Paolini, Ambra and Martinelli, Silvia and Maffei, Rossana and Riva, Giovanni and Nasillo, Vincenzo and Sarti, Mario and Trenti, Tommaso and Comoli, Patrizia and Tagliafico, Enrico and Manfredini, Rossella and Eccher, Albino and Lagreca, Ivana and Barozzi, Patrizia and Potenza, Leonardo and Marasca, Roberto and Candoni, Anna and Luppi, Mario and Forghieri, Fabio},\n\tmonth = dec,\n\tyear = {2023},\n\tpmid = {38112426},\n\tnote = {Publisher: Taylor \\& Francis\n\\_eprint: https://doi.org/10.1080/10428194.2023.2294695},\n\tkeywords = {AML, Acute myeloid leukaemia, DDM, MYS, Myeloid, Myeloid Solution, NPM1},\n\tpages = {1--5},\n}\n\n

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\n \n\n \n \n \n \n \n \n GIInger predicts homologous recombination deficiency and patient response to PARPi treatment from shallow genomic profiles.\n \n \n \n \n\n\n \n Pozzorini, C.; Andre, G.; Coletta, T.; Buisson, A.; Bieler, J.; Ferrer, L.; Kempfer, R.; Saintigny, P.; Harlé, A.; Vacirca, D.; Barberis, M.; Gilson, P.; Roma, C.; Saitta, A.; Smith, E.; Barras, F. C.; Ripol, L.; Fritzsche, M.; Marques, A. C.; Alkodsi, A.; Marin, R.; Normanno, N.; Grimm, C.; Müllauer, L.; Harter, P.; Pignata, S.; Gonzalez-Martin, A.; Denison, U.; Fujiwara, K.; Vergote, I.; Colombo, N.; Willig, A.; Pujade-Lauraine, E.; Just, P.; Ray-Coquard, I.; and Xu, Z.\n\n\n \n\n\n\n Cell Reports Medicine, 4(12). December 2023.\n Publisher: Elsevier\n\n\n\n
\n\n\n\n \n \n $\"GIInger$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{pozzorini_giinger_2023,\n\ttitle = {{GIInger} predicts homologous recombination deficiency and patient response to {PARPi} treatment from shallow genomic profiles},\n\tvolume = {4},\n\tissn = {2666-3791},\n\turl = {https://www.cell.com/cell-reports-medicine/abstract/S2666-3791(23)00561-X},\n\tdoi = {10.1016/j.xcrm.2023.101344},\n\tlanguage = {English},\n\tnumber = {12},\n\turldate = {2024-01-23},\n\tjournal = {Cell Reports Medicine},\n\tauthor = {Pozzorini, Christian and Andre, Gregoire and Coletta, Tommaso and Buisson, Adrien and Bieler, Jonathan and Ferrer, Loïc and Kempfer, Rieke and Saintigny, Pierre and Harlé, Alexandre and Vacirca, Davide and Barberis, Massimo and Gilson, Pauline and Roma, Cristin and Saitta, Alexandra and Smith, Ewan and Barras, Floriane Consales and Ripol, Lucia and Fritzsche, Martin and Marques, Ana Claudia and Alkodsi, Amjad and Marin, Ray and Normanno, Nicola and Grimm, Christoph and Müllauer, Leonhard and Harter, Philipp and Pignata, Sandro and Gonzalez-Martin, Antonio and Denison, Ursula and Fujiwara, Keiichi and Vergote, Ignace and Colombo, Nicoletta and Willig, Adrian and Pujade-Lauraine, Eric and Just, Pierre-Alexandre and Ray-Coquard, Isabelle and Xu, Zhenyu},\n\tmonth = dec,\n\tyear = {2023},\n\tpmid = {38118421},\n\tnote = {Publisher: Elsevier},\n\tkeywords = {HRD, PARPi, biomarker, breast cancer, cancer, convolutional neural network, homologous recombination deficiency, low-pass whole-genome sequencing, lpWGS, ovarian cancer},\n}\n\n

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\n \n\n \n \n \n \n \n \n Compilation of Genotype and Phenotype Data in GCDH-LOVD for Variant Classification and Further Application.\n \n \n \n \n\n\n \n Tibelius, A.; Evers, C.; Oeser, S.; Rinke, I.; Jauch, A.; and Hinderhofer, K.\n\n\n \n\n\n\n Genes, 14(12): 2218. December 2023.\n Number: 12 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Compilation$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{tibelius_compilation_2023,\n\ttitle = {Compilation of {Genotype} and {Phenotype} {Data} in {GCDH}-{LOVD} for {Variant} {Classification} and {Further} {Application}},\n\tvolume = {14},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2073-4425},\n\turl = {https://www.mdpi.com/2073-4425/14/12/2218},\n\tdoi = {10.3390/genes14122218},\n\tabstract = {Glutaric aciduria type 1 (GA-1) is a rare but treatable autosomal-recessive neurometabolic disorder of lysin metabolism caused by biallelic pathogenic variants in glutaryl-CoA dehydrogenase gene (GCDH) that lead to deficiency of GCDH protein. Without treatment, this enzyme defect causes a neurological phenotype characterized by movement disorder and cognitive impairment. Based on a comprehensive literature search, we established a large dataset of GCDH variants using the Leiden Open Variation Database (LOVD) to summarize the known genotypes and the clinical and biochemical phenotypes associated with GA-1. With these data, we developed a GCDH-specific variation classification framework based on American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines. We used this framework to reclassify published variants and to describe their geographic distribution, both of which have practical implications for the molecular genetic diagnosis of GA-1. The freely available GCDH-specific LOVD dataset provides a basis for diagnostic laboratories and researchers to further optimize their knowledge and molecular diagnosis of this rare disease.},\n\tlanguage = {en},\n\tnumber = {12},\n\turldate = {2024-01-23},\n\tjournal = {Genes},\n\tauthor = {Tibelius, Alexandra and Evers, Christina and Oeser, Sabrina and Rinke, Isabelle and Jauch, Anna and Hinderhofer, Katrin},\n\tmonth = dec,\n\tyear = {2023},\n\tnote = {Number: 12\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Alamut, Alamut Visual Plus, Alamut Visual Plus v1.6.1, GCDH, LOVD, geographic distribution, glutaric acidemia, glutaric aciduria, glutaryl-CoA dehydrogenase, inborn errors of metabolism, variant classification, variant interpretation, variation database},\n\tpages = {2218},\n}\n\n

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\n \n\n \n \n \n \n \n \n Cyclosporine A micellar nasal spray characterization and antiviral action against SARS-CoV-2.\n \n \n \n \n\n\n \n Guareschi, F.; Del Favero, E.; Ricci, C.; Cantù, L.; Brandolini, M.; Sambri, V.; Nicoli, S.; Pescina, S.; D'Angelo, D.; Rossi, I.; Buttini, F.; Bettini, R.; and Sonvico, F.\n\n\n \n\n\n\n European Journal of Pharmaceutical Sciences, 193: 106673. December 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Cyclosporine$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{guareschi_cyclosporine_2023,\n\ttitle = {Cyclosporine {A} micellar nasal spray characterization and antiviral action against {SARS}-{CoV}-2},\n\tvolume = {193},\n\tissn = {0928-0987},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0928098723003019},\n\tdoi = {10.1016/j.ejps.2023.106673},\n\tabstract = {The upper airways represent the point of entrance from where Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection spreads to the lungs. In the present work, α-tocopheryl-polyethylene-glycol succinate (TPGS) micelles loaded with cyclosporine A (CSA) were developed for nasal administration to prevent or treat the viral infection in the very first phases. The behavior of the micelles in presence of simulated nasal mucus was investigated in terms of stability and mucopenetration rate, evidencing long-term stability and fast diffusion across the glycoproteins matrix. Moreover, the spray characteristics of the micellar formulation and deposition profile in a silicon nasal model were studied using three nasal spray devices. Results allowed to identify the nasal spray pump (BiVax, Aptar) able to provide the wider and uniform deposition of the nasal cavity. The cyclosporine A micelles antiviral activity against SARS-CoV-2 was tested on the Omicron BA.1 variant using Vero E6 cells with protocols simulating treatment before, during and after the infection of the upper airways. Complete viral inactivation was observed for the cyclosporine-loaded micelles while a very low activity was evidenced for the non-formulated drug, suggesting a synergistic activity of the drug and the formulation. In conclusion, this work showed that the developed cyclosporine A-loaded micellar formulations have the potential to be clinically effective against a wide spectrum of coronavirus variants.},\n\turldate = {2024-01-23},\n\tjournal = {European Journal of Pharmaceutical Sciences},\n\tauthor = {Guareschi, Fabiola and Del Favero, Elena and Ricci, Caterina and Cantù, Laura and Brandolini, Martina and Sambri, Vittorio and Nicoli, Sara and Pescina, Silvia and D'Angelo, Davide and Rossi, Irene and Buttini, Francesca and Bettini, Ruggero and Sonvico, Fabio},\n\tmonth = dec,\n\tyear = {2023},\n\tkeywords = {Antiviral activity, Cyclosporine A, DDM, Nasal delivery, Nasal spray devices, SARS-CoV-2, TPGS micelles},\n\tpages = {106673},\n}\n\n

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\n \n\n \n \n \n \n \n \n Role of genetic investigation in the diagnosis of short stature in a cohort of Italian children.\n \n \n \n \n\n\n \n Cavarzere, P.; Pietrobelli, A.; Gandini, A.; Munari, S.; Baffico, A. M.; Maffei, M.; Gaudino, R.; Guzzo, A.; Arrigoni, M.; Coviello, D.; Piacentini, G.; and Antoniazzi, F.\n\n\n \n\n\n\n Journal of Endocrinological Investigation. December 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Role$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{cavarzere_role_2023,\n\ttitle = {Role of genetic investigation in the diagnosis of short stature in a cohort of {Italian} children},\n\tissn = {1720-8386},\n\turl = {https://doi.org/10.1007/s40618-023-02243-9},\n\tdoi = {10.1007/s40618-023-02243-9},\n\tabstract = {Short stature (SS) is defined as height more than 2 standard deviations below the mean for age and sex. Hypothyroidism, celiac disease, growth hormone deficiency, hormonal abnormalities, and genetic conditions are among its causes. A wide range of conditions often due to largely unknown genetic variants can elude conventional diagnostic workup.},\n\tlanguage = {en},\n\turldate = {2024-01-23},\n\tjournal = {Journal of Endocrinological Investigation},\n\tauthor = {Cavarzere, P. and Pietrobelli, A. and Gandini, A. and Munari, S. and Baffico, A. M. and Maffei, M. and Gaudino, R. and Guzzo, A. and Arrigoni, M. and Coviello, D. and Piacentini, G. and Antoniazzi, F.},\n\tmonth = dec,\n\tyear = {2023},\n\tkeywords = {Custom, Custom Panel, DDM, Genetic analysis, Growth, Next-generation sequencing (NGS), Short stature (SS), Variants of uncertain significance (VUS)},\n}\n\n

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\n \n\n \n \n \n \n \n \n Contrastive image adaptation for acquisition shift reduction in medical imaging.\n \n \n \n \n\n\n \n Hognon, C.; Conze, P.; Bourbonne, V.; Gallinato, O.; Colin, T.; Jaouen, V.; and Visvikis, D.\n\n\n \n\n\n\n Artificial Intelligence in Medicine. December 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Contrastive$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{hognon_contrastive_2023,\n\ttitle = {Contrastive image adaptation for acquisition shift reduction in medical imaging},\n\turl = {https://imt-atlantique.hal.science/hal-04334344},\n\tabstract = {The domain shift, or acquisition shift in medical imaging, is responsible for potentially harmful differences between development and deployment conditions of medical image analysis techniques. There is a growing need in the community for advanced methods that could mitigate this issue better than conventional approaches. In this paper, we consider configurations in which we can expose a learning-based pixel level adaptor to a large variability of unlabeled images during its training, i.e. sufficient to span the acquisition shift expected during the training or testing of a downstream task model. We leverage the ability of convolutional architectures to efficiently learn domain-agnostic features and train a many-to-one unsupervised mapping between a source collection of heterogeneous images from multiple unknown domains subjected to the acquisition shift and a homogeneous subset of this source set of lower cardinality, potentially constituted of a single image. To this end, we propose a new cycle-free image-to-image architecture based on a combination of three loss functions : a contrastive PatchNCE loss, an adversarial loss and an edge preserving loss allowing for rich domain adaptation to the target image even under strong domain imbalance and low data regimes. Experiments support the interest of the proposed contrastive image adaptation approach for the regularization of downstream deep supervised segmentation and cross-modality synthesis models.},\n\tlanguage = {en},\n\turldate = {2024-01-23},\n\tjournal = {Artificial Intelligence in Medicine},\n\tauthor = {Hognon, Clément and Conze, Pierre-Henri and Bourbonne, Vincent and Gallinato, Olivier and Colin, Thierry and Jaouen, Vincent and Visvikis, Dimitris},\n\tmonth = dec,\n\tyear = {2023},\n\tkeywords = {Radiomics},\n}\n\n

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\n \n\n \n \n \n \n \n Late-Onset Autoimmune Lymphoproliferative Syndrome in a Costa Rican Woman.\n \n \n \n\n\n \n Alfaro-Murillo, A.; Correa-Jimenez, O.; González-Chapa, J.; Viloria-González, T.; Calvo-Solís, M.; and Maradei-Anaya, S.\n\n\n \n\n\n\n Cureus, 15(12): e50226. December 2023.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{alfaro-murillo_late-onset_2023,\n\ttitle = {Late-{Onset} {Autoimmune} {Lymphoproliferative} {Syndrome} in a {Costa} {Rican} {Woman}},\n\tvolume = {15},\n\tissn = {2168-8184},\n\tdoi = {10.7759/cureus.50226},\n\tabstract = {Autoimmune lymphoproliferative syndrome (ALPS) is a primary immune regulatory disorder (PIRD). This disease usually develops during childhood. However, atypically, some cases may have their onset in adulthood. We report the case of a 44-year-old woman with a history of autoimmune hemolytic anemia at 33 years old. The patient presented due to asthenia and a large, painful lymph node in the left axillary region for the last four months. Enlargement of the axillary and inguinal lymph nodes was found by mammography, breast, and abdominal ultrasounds. An excisional biopsy of the axillary lymph node conglomerate did not document immunophenotypical alterations of T or B lymphocytes but showed progressive transformation of germinal centers with reactive follicular hyperplasia. The lymph node cytometry did not show a malignant phenotype. The immunological work-up documented IgG and IgA hypergammaglobulinemia and slightly decreased IgM; the B cell immunophenotype documented a slight increase in CD21low B cells and decreased memory B cells. The blood count was normal. The T cell compartment evidenced 27\\% CD3+/αβ+/γδ-/CD4-/CD8- of the total T CD3+ cells and 15\\% of the total lymphocytes. A pathogenic heterozygous variant in the FAS gene, exon 9, c.785T{\\textgreater}A (p.Ile262Asn), was documented. This variant has not been previously described. This case highlights the importance of considering the diagnosis of ALPS even in adulthood. Genetic conditions such as incomplete penetrance or variable expressivity that depend on factors that are not entirely clear in ALPS, such as epigenetics and environmental factors, among others, could generate the onset of this disease in adulthood in a smaller number of patients.},\n\tlanguage = {eng},\n\tnumber = {12},\n\tjournal = {Cureus},\n\tauthor = {Alfaro-Murillo, Alberto and Correa-Jimenez, Oscar and González-Chapa, Jorge and Viloria-González, Tibisay and Calvo-Solís, Melvin and Maradei-Anaya, Silvia},\n\tmonth = dec,\n\tyear = {2023},\n\tpmid = {38077666},\n\tpmcid = {PMC10710266},\n\tkeywords = {CES, Clinical Exome Solution, DDM, atypical lym, auto immune, autoimmune hemolytic anemia (aiha), clinical exome sequencing (CES), length of spleen, lymph node-negative},\n\tpages = {e50226},\n}\n\n

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\n \n\n \n \n \n \n \n \n Report of a Novel Homozygous Intragenic DCC Duplication and a Review of Literature of Developmental Split-Brain Syndrome aka Horizontal Gaze Palsy with Progressive Scoliosis-2 with Impaired Intellectual Development Syndrome.\n \n \n \n \n\n\n \n Rahikkala, E.; Väisänen, T.; Ojala, L.; Pohjola, P.; Toivonen, M.; Parkkola, R.; and Haanpää, M. K.\n\n\n \n\n\n\n Molecular Syndromology,1–7. December 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Report$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{rahikkala_report_2023,\n\ttitle = {Report of a {Novel} {Homozygous} {Intragenic} {DCC} {Duplication} and a {Review} of {Literature} of {Developmental} {Split}-{Brain} {Syndrome} aka {Horizontal} {Gaze} {Palsy} with {Progressive} {Scoliosis}-2 with {Impaired} {Intellectual} {Development} {Syndrome}},\n\tissn = {1661-8769},\n\turl = {https://doi.org/10.1159/000534772},\n\tdoi = {10.1159/000534772},\n\tabstract = {Introduction: Horizontal gaze palsy with progressive scoliosis-2 (HGPPS2, MIM 617542) with impaired intellectual development aka developmental split-brain syndrome is an ultra-rare congenital disorder caused by pathogenic biallelic variants in the deleted in colorectal cancer (DCC) gene. Case Presentation: We report the clinical and genetic characterization of a Syrian patient with a HGPPS2 phenotype and review the previously published cases of HGPPS2. The genetic screening was performed using exome sequencing on Illumina platform. Genetic analysis revealed a novel DCC c.(?\\_1912)\\_(2359\\_?)dup, p.(Ser788Tyrfs*4) variant segregating recessively in the family. This type of variant has not been described previously in the HGPPS2 patients. To date, including the case reported here, three different homozygous pathogenic frameshift variants, one homozygous missense variant, and an intragenic duplication in the DCC gene have been reported in 8 patients with the HGPPS2 syndrome. Conclusion: The analysis of duplications and deletions in the DCC should be included in the routine genetic diagnostic evaluation of patients with suspected HGPPS2. This report expands the knowledge of phenotypic and genotypic spectrum of pathogenic variants causing HGPPS2.},\n\turldate = {2024-01-23},\n\tjournal = {Molecular Syndromology},\n\tauthor = {Rahikkala, Elisa and Väisänen, Taneli and Ojala, Liisa and Pohjola, Pia and Toivonen, Minna and Parkkola, Riitta and Haanpää, Maria K.},\n\tmonth = dec,\n\tyear = {2023},\n\tkeywords = {Custom, Custom Cancer Panel, DCC, DDM},\n\tpages = {1--7},\n}\n\n

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\n \n\n \n \n \n \n \n \n Newborn Genetic Screening—Still a Role for Sanger Sequencing in the Era of NGS.\n \n \n \n \n\n\n \n Hogner, S.; Lundman, E.; Strand, J.; Ytre-Arne, M. E.; Tangeraas, T.; and Stray-Pedersen, A.\n\n\n \n\n\n\n International Journal of Neonatal Screening, 9(4): 67. December 2023.\n Number: 4 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Newborn$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{hogner_newborn_2023,\n\ttitle = {Newborn {Genetic} {Screening}—{Still} a {Role} for {Sanger} {Sequencing} in the {Era} of {NGS}},\n\tvolume = {9},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2409-515X},\n\turl = {https://www.mdpi.com/2409-515X/9/4/67},\n\tdoi = {10.3390/ijns9040067},\n\tabstract = {In the Norwegian newborn screening (NBS) program, genetic testing has been implemented as a second or third tier method for the majority of NBS disorders, significantly increasing positive predictive value (PPV). DNA is extracted from dried blood spot (DBS) filter cards. For monogenic disorders caused by variants in one single gene or a few genes only, Sanger sequencing has been shown to be the most time- and cost-efficient method to use. Here, we present the Sanger sequencing method, including primer sequences and the genetic test algorithms, currently used in the Norwegian newborn screening program.},\n\tlanguage = {en},\n\tnumber = {4},\n\turldate = {2024-01-23},\n\tjournal = {International Journal of Neonatal Screening},\n\tauthor = {Hogner, Silje and Lundman, Emma and Strand, Janne and Ytre-Arne, Mari Eknes and Tangeraas, Trine and Stray-Pedersen, Asbjørg},\n\tmonth = dec,\n\tyear = {2023},\n\tnote = {Number: 4\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Alamut Visual, Sanger sequencing, dried bloodspots, extraction, newborn screening},\n\tpages = {67},\n}\n\n

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\n \n\n \n \n \n \n \n \n Sarco/endoplasmic reticulum calcium ATPase 3 (SERCA3) expression in gastrointestinal stromal tumours.\n \n \n \n \n\n\n \n Adle-Biassette, H.; Ricci, R.; Martin, A.; Martini, M.; Ravegnini, G.; Kaci, R.; Gélébart, P.; Poirot, B.; Sándor, Z.; Lehman-Che, J.; Tóth, E.; and Papp, B.\n\n\n \n\n\n\n Pathology. December 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Sarco/endoplasmic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{adle-biassette_sarcoendoplasmic_2023,\n\ttitle = {Sarco/endoplasmic reticulum calcium {ATPase} 3 ({SERCA3}) expression in gastrointestinal stromal tumours},\n\tissn = {0031-3025},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0031302523003094},\n\tdoi = {10.1016/j.pathol.2023.10.012},\n\tabstract = {Accurate characterisation of gastrointestinal stromal tumours (GIST) is important for prognosis and the choice of targeted therapies. Histologically the diagnosis relies on positive immunostaining of tumours for KIT (CD117) and DOG1. Here we report that GISTs also abundantly express the type 3 Sarco/Endoplasmic Reticulum Calcium ATPase (SERCA3). SERCA enzymes transport calcium ions from the cytosol into the endoplasmic reticulum and play an important role in regulating the intensity and the periodicity of calcium-induced cell activation. GISTs from various localisations, histological and molecular subtypes or risk categories were intensely immunopositive for SERCA3 with the exception of PDGFRA-mutated cases where expression was high or moderate. Strong SERCA3 expression was observed also in normal and hyperplastic interstitial cells of Cajal. Decreased SERCA3 expression in GIST was exceptionally observed in a zonal pattern, where CD117 staining was similarly decreased, reflecting clonal heterogeneity. In contrast to GIST, SERCA3 immunostaining of spindle cell tumours and other gastrointestinal tumours resembling GIST was negative or weak. In conclusion, SERCA3 immunohistochemistry may be useful for the diagnosis of GIST with high confidence, when used as a third marker in parallel with KIT and DOG1. Moreover, SERCA3 immunopositivity may be particularly helpful in cases with negative or weak KIT or DOG1 staining, a situation that may be encountered de novo, or during the spontaneous or therapy-induced clonal evolution of GIST.},\n\turldate = {2024-01-23},\n\tjournal = {Pathology},\n\tauthor = {Adle-Biassette, Homa and Ricci, Riccardo and Martin, Antoine and Martini, Maurizio and Ravegnini, Gloria and Kaci, Rachid and Gélébart, Pascal and Poirot, Brigitte and Sándor, Zsuzsanna and Lehman-Che, Jacqueline and Tóth, Erika and Papp, Bela},\n\tmonth = dec,\n\tyear = {2023},\n\tkeywords = {DDM, Gastrointestinal stromal tumour, STS, Solid Tumor Solution, calcium, endoplasmic reticulum, immunohistochemistry, interstitial cells of Cajal, marker, sarco/endoplasmic reticulum calcium ATPase},\n}\n\n

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\n \n\n \n \n \n \n \n \n A case of autoimmune lymphoproliferative syndrome with a novel de novo FAS variant.\n \n \n \n \n\n\n \n Ozcelik, F.; Aslan, K.; Gok, V.; Ari, M. B.; Ozcan, A.; Eken, A.; Ünal, E.; Ozkul, Y.; and Dundar, M.\n\n\n \n\n\n\n Pediatric Hematology and Oncology, 0(0): 1–9. December 2023.\n Publisher: Taylor & Francis _eprint: https://doi.org/10.1080/08880018.2023.2286967\n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{ozcelik_case_2023,\n\ttitle = {A case of autoimmune lymphoproliferative syndrome with a novel de novo {FAS} variant},\n\tvolume = {0},\n\tissn = {0888-0018},\n\turl = {https://doi.org/10.1080/08880018.2023.2286967},\n\tdoi = {10.1080/08880018.2023.2286967},\n\tnumber = {0},\n\turldate = {2024-01-23},\n\tjournal = {Pediatric Hematology and Oncology},\n\tauthor = {Ozcelik, Firat and Aslan, Kubra and Gok, Veysel and Ari, Mucahit Bilgehan and Ozcan, Alper and Eken, Ahmet and Ünal, Ekrem and Ozkul, Yusuf and Dundar, Munis},\n\tmonth = dec,\n\tyear = {2023},\n\tpmid = {38047450},\n\tnote = {Publisher: Taylor \\& Francis\n\\_eprint: https://doi.org/10.1080/08880018.2023.2286967},\n\tkeywords = {Auto-immunological profile, CES, Clinical Exome Solution, Lymphadenopathy, Lymphoma, clinical exome sequencing (CES)},\n\tpages = {1--9},\n}\n\n

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\n \n\n \n \n \n \n \n \n A Bioinformatics Toolkit for Next-Generation Sequencing in Clinical Oncology.\n \n \n \n \n\n\n \n Cabello-Aguilar, S.; Vendrell, J. A.; and Solassol, J.\n\n\n \n\n\n\n Current Issues in Molecular Biology, 45(12): 9737–9752. December 2023.\n Number: 12 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{cabello-aguilar_bioinformatics_2023,\n\ttitle = {A {Bioinformatics} {Toolkit} for {Next}-{Generation} {Sequencing} in {Clinical} {Oncology}},\n\tvolume = {45},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {1467-3045},\n\turl = {https://www.mdpi.com/1467-3045/45/12/608},\n\tdoi = {10.3390/cimb45120608},\n\tabstract = {Next-generation sequencing (NGS) has taken on major importance in clinical oncology practice. With the advent of targeted therapies capable of effectively targeting specific genomic alterations in cancer patients, the development of bioinformatics processes has become crucial. Thus, bioinformatics pipelines play an essential role not only in the detection and in identification of molecular alterations obtained from NGS data but also in the analysis and interpretation of variants, making it possible to transform raw sequencing data into meaningful and clinically useful information. In this review, we aim to examine the multiple steps of a bioinformatics pipeline as used in current clinical practice, and we also provide an updated list of the necessary bioinformatics tools. This resource is intended to assist researchers and clinicians in their genetic data analyses, improving the precision and efficiency of these processes in clinical research and patient care.},\n\tlanguage = {en},\n\tnumber = {12},\n\turldate = {2024-01-23},\n\tjournal = {Current Issues in Molecular Biology},\n\tauthor = {Cabello-Aguilar, Simon and Vendrell, Julie A. and Solassol, Jérôme},\n\tmonth = dec,\n\tyear = {2023},\n\tnote = {Number: 12\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Benchmark, CNV, DDM, MSI, MicroSatellite Instability analysis (MSI), NGS, SNV, bioinformatics, clinical oncology, microsatellite instability, pipeline, targeted therapy},\n\tpages = {9737--9752},\n}\n\n

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\n \n\n \n \n \n \n \n \n Short-read whole genome sequencing identifies causative variants in most individuals with previously unexplained aniridia.\n \n \n \n \n\n\n \n Hall, H. N.; Parry, D.; Halachev, M.; Williamson, K. A.; Donnelly, K.; Parada, J. C.; Bhatia, S.; Joseph, J.; Holden, S.; Prescott, T. E.; Bitoun, P.; Kirk, E. P.; Newbury-Ecob, R.; Lachlan, K.; Bernar, J.; Heyningen, V. v.; FitzPatrick, D. R.; and Meynert, A.\n\n\n \n\n\n\n Journal of Medical Genetics. November 2023.\n Publisher: BMJ Publishing Group Ltd Section: Developmental defects\n\n\n\n
\n\n\n\n \n \n $\"Short-read$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{hall_short-read_2023,\n\ttitle = {Short-read whole genome sequencing identifies causative variants in most individuals with previously unexplained aniridia},\n\tcopyright = {© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.},\n\tissn = {0022-2593, 1468-6244},\n\turl = {https://jmg.bmj.com/content/early/2023/11/30/jmg-2023-109181},\n\tdoi = {10.1136/jmg-2023-109181},\n\tabstract = {Background Classic aniridia is a highly penetrant autosomal dominant disorder characterised by congenital absence of the iris, foveal hypoplasia, optic disc anomalies and progressive opacification of the cornea. {\\textgreater}90\\% of cases of classic aniridia are caused by heterozygous, loss-of-function variants affecting the PAX6 locus.\nMethods Short-read whole genome sequencing was performed on 51 (39 affected) individuals from 37 different families who had screened negative for mutations in the PAX6 coding region.\nResults Likely causative mutations were identified in 22 out of 37 (59\\%) families. In 19 out of 22 families, the causative genomic changes have an interpretable deleterious impact on the PAX6 locus. Of these 19 families, 1 has a novel heterozygous PAX6 frameshift variant missed on previous screens, 4 have single nucleotide variants (SNVs) (one novel) affecting essential splice sites of PAX6 5′ non-coding exons and 2 have deep intronic SNV (one novel) resulting in gain of a donor splice site. In 12 out of 19, the causative variants are large-scale structural variants; 5 have partial or whole gene deletions of PAX6, 3 have deletions encompassing critical PAX6 cis-regulatory elements, 2 have balanced inversions with disruptive breakpoints within the PAX6 locus and 2 have complex rearrangements disrupting PAX6. The remaining 3 of 22 families have deletions encompassing FOXC1 (a known cause of atypical aniridia). Seven of the causative variants occurred de novo and one cosegregated with familial aniridia. We were unable to establish inheritance status in the remaining probands. No plausibly causative SNVs were identified in PAX6 cis-regulatory elements.\nConclusion Whole genome sequencing proves to be an effective diagnostic test in most individuals with previously unexplained aniridia.},\n\tlanguage = {en},\n\turldate = {2024-01-23},\n\tjournal = {Journal of Medical Genetics},\n\tauthor = {Hall, Hildegard Nikki and Parry, David and Halachev, Mihail and Williamson, Kathleen A. and Donnelly, Kevin and Parada, Jose Campos and Bhatia, Shipra and Joseph, Jeffrey and Holden, Simon and Prescott, Trine E. and Bitoun, Pierre and Kirk, Edwin P. and Newbury-Ecob, Ruth and Lachlan, Katherine and Bernar, Juan and Heyningen, Veronica van and FitzPatrick, David R. and Meynert, Alison},\n\tmonth = nov,\n\tyear = {2023},\n\tpmid = {38050128},\n\tnote = {Publisher: BMJ Publishing Group Ltd\nSection: Developmental defects},\n\tkeywords = {Alamut, Eye Diseases, Genetic Testing, Mutation},\n}\n\n

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\n \n\n \n \n \n \n \n \n Integrated Molecular Characterization of HER2-Low Breast Cancer Using Next Generation Sequencing (NGS).\n \n \n \n \n\n\n \n Merlin, J.; Husson, M.; Sahki, N.; Gilson, P.; Massard, V.; Harlé, A.; and Leroux, A.\n\n\n \n\n\n\n Biomedicines, 11(12): 3164. November 2023.\n Number: 12 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Integrated$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{merlin_integrated_2023,\n\ttitle = {Integrated {Molecular} {Characterization} of {HER2}-{Low} {Breast} {Cancer} {Using} {Next} {Generation} {Sequencing} ({NGS})},\n\tvolume = {11},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2227-9059},\n\turl = {https://www.mdpi.com/2227-9059/11/12/3164},\n\tdoi = {10.3390/biomedicines11123164},\n\tabstract = {Based on immunohistochemistry (IHC) and in situ hybridization (ISH), HER2-low breast cancers (BC) subtype—defined as IHC1+ or IHC2+/ISH− tumors—emerged and represent more than half of all BC. We evaluated the performance of NGS for integrated molecular characterization of HER2-low BC, including identification of actionable molecular targets, copy number variation (CNV), and microsatellite instability (MSI) analysis. Thirty-one BC specimens (11 HER2+, 10 HER2−, and 10 HER2-low) were routinely analyzed using IHC and ISH, and were selected and analyzed using NGS for gene mutations including ESR1, PIK3CA, AKT1, ERBB2, TP53, BRCA1, and BRCA2, CNV, and MSI. CNV values for the ERBB2 gene were significantly (p {\\textless} 0.001) different between HER2+, and either HER2-low or HER2− tumors with mean values of 7.8 (SD = 6.8), 1.9 (SD = 0.3), and 2.0 (SD = 0.3), respectively. Using 3.25 as the cutoff value, 96.8\\% overall concordance of HER2 status was achieved between IHC and NGS compared to IHC and ISH. Using NGS, gene mutations and amplifications were detected in 68\\% (21/31) and 19\\% (6/31) of the cases, respectively. One case of MSI was detected in a HER2-negative and ISH unamplified case. Beside IHC, NGS allows the identification of HER2-low subtype simultaneously, with the detection of multiple actionable gene mutations being helpful for molecular board treatment selection.},\n\tlanguage = {en},\n\tnumber = {12},\n\turldate = {2024-01-23},\n\tjournal = {Biomedicines},\n\tauthor = {Merlin, Jean-Louis and Husson, Marie and Sahki, Nassim and Gilson, Pauline and Massard, Vincent and Harlé, Alexandre and Leroux, Agnès},\n\tmonth = nov,\n\tyear = {2023},\n\tnote = {Number: 12\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Breast cancer, Custom Panel, Custom STS, DDM, HER2-low, antibody-drug conjugate, copy number variation, molecular diagnosis, next generation sequencing},\n\tpages = {3164},\n}\n\n

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\n \n\n \n \n \n \n \n \n Direct Comparative Analysis of a Pharmacogenomics Panel with PacBio Hifi® Long-Read and Illumina Short-Read Sequencing.\n \n \n \n \n\n\n \n Barthélémy, D.; Belmonte, E.; Pilla, L. D.; Bardel, C.; Duport, E.; Gautier, V.; and Payen, L.\n\n\n \n\n\n\n Journal of Personalized Medicine, 13(12): 1655. November 2023.\n Number: 12 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Direct$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{barthelemy_direct_2023,\n\ttitle = {Direct {Comparative} {Analysis} of a {Pharmacogenomics} {Panel} with {PacBio} {Hifi}® {Long}-{Read} and {Illumina} {Short}-{Read} {Sequencing}},\n\tvolume = {13},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2075-4426},\n\turl = {https://www.mdpi.com/2075-4426/13/12/1655},\n\tdoi = {10.3390/jpm13121655},\n\tabstract = {Background: Pharmacogenetics (PGx) aims to determine genetic signatures that can be used in clinical settings to individualize treatment for each patient, including anti-cancer drugs, anti-psychotics, and painkillers. Taken together, a better understanding of the impacts of genetic variants on the corresponding protein function or expression permits the prediction of the pharmacological response: responders, non-responders, and those with adverse drug reactions (ADRs). Objective: This work provides a comparison between innovative long-read sequencing (LRS) and short-read sequencing (SRS) techniques. Methods and Materials: The gene panel captured using PacBio HiFi® sequencing was tested on thirteen clinical samples on GENTYANE’s platform. SRS, using a comprehensive pharmacogenetics panel, was performed in routine settings at the Civil Hospitals of Lyon. We focused on complex regions analysis, including copy number variations (CNVs), structural variants, repeated regions, and phasing-haplotyping for three key pharmacogenes: CYP2D6, UGT1A1, and NAT2. Results: Variants and the corresponding expected star (*) alleles were reported. Although only 38.4\\% concordance was found for haplotype determination and 61.5\\% for diplotype, this did not affect the metabolism scoring. A better accuracy of LRS was obtained for the detection of the CYP2D6*5 haplotype in the presence of the duplicated wild-type CYP2D6*2 form. A total concordance was performed for UGT1A1 TA repeat detection. Direct phasing using the LRS approach allowed us to correct certain NAT2 profiles. Conclusions: Combining an optimized variant-calling pipeline and with direct phasing analysis, LRS is a robust technique for PGx analysis that can minimize the risk of mis-haplotyping.},\n\tlanguage = {en},\n\tnumber = {12},\n\turldate = {2024-01-23},\n\tjournal = {Journal of Personalized Medicine},\n\tauthor = {Barthélémy, David and Belmonte, Elodie and Pilla, Laurie Di and Bardel, Claire and Duport, Eve and Gautier, Veronique and Payen, Léa},\n\tmonth = nov,\n\tyear = {2023},\n\tnote = {Number: 12\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Benchmark, CNV, DDM, NGS, copy number variation (CNV), haplotyping, long-read sequencing (LSR), pharmacogenetics, phasing, short-read sequencing (SRS)},\n\tpages = {1655},\n}\n\n

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\n \n\n \n \n \n \n \n \n Quantification of JAK2 V167F in Patients with Myeloproliferative Neoplasms: Comparison of NGS and Digital PCR with Quantitative PCR.\n \n \n \n \n\n\n \n Stuckey, R.; Santana, G.; Florido, Y.; Segura-Díaz, A.; Gómez-Casares, M. T.; and Bilbao-Sieyro, C.\n\n\n \n\n\n\n Blood, 142: 6396. November 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Quantification$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{stuckey_quantification_2023,\n\tseries = {65th {ASH} {Annual} {Meeting} {Abstracts}},\n\ttitle = {Quantification of {JAK2} {V167F} in {Patients} with {Myeloproliferative} {Neoplasms}: {Comparison} of {NGS} and {Digital} {PCR} with {Quantitative} {PCR}},\n\tvolume = {142},\n\tissn = {0006-4971},\n\tshorttitle = {Quantification of {JAK2} {V167F} in {Patients} with {Myeloproliferative} {Neoplasms}},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0006497123129934},\n\tdoi = {10.1182/blood-2023-188510},\n\tabstract = {Introduction: JAK2 V617F is the most common mutation in the Philadelphia-negative myeloproliferative neoplasms (MPN), detected in 97\\% of polycythemia vera (PV), and approximately 55\\% of essential thrombocythemia (ET) and primary myelofibrosis (PMF) cases. According to the WHO, JAK2 V617F positivity is a major criteria for PV, ET or PMF diagnosis. But JAK2 V617F quantification at diagnosis could be useful since a high allelic frequency (or VAF) has been associated with increased symptom burden in PV, risk of thrombotic events in ET and progression in PMF. The current gold standard technique for JAK2 V617F quantification is allele-specific quantitative PCR (qPCR). However, digital PCR (dPCR) is increasingly being employed since it permits absolute quantification of JAK2 V617F without the need for a standard curve. QPCR vs. dPCR comparisons have shown high conformance between the two methods. Moreover, next-generation sequencing technologies (NGS) are increasingly used for MPN diagnosis. The aim of this study was to evaluate the concordance between dPCR and NGS for JAK2 V617F quantification at diagnosis. Methods: JAK2 V617F was quantified in the same sample of genomic DNA, extracted from total leukocytes from peripheral blood or bone marrow at diagnosis, by digital PCR (dPCR) and by NGS. The Absolute Q™ Liquid Biopsy dPCR Assay (JAK2 12600) was used in the QuantStudio™ Absolute Q™ Digital PCR System (Applied Biosystems) with 25 ng DNA. This assay quantifies the number of JAK2 WT-VIC and JAK2 V617F-FAM positive signals in 20000 partitions, determined as copies JAK2 V617F/µl input sample, and expressed as percentage VAF, with a limit of detection of 0.1\\%. NGS was performed with the MiSeq (Illumina) platform and the targeted 30-gene panel Myeloid Solution™ (SOPHiA GENETICS) using 200 ng DNA. VAF was determined as the number of variant reads divided by the number of total reads (reported as a percentage), with a limit of detection of 2.5\\%. Statistical analyses were performed using R-commander version 2.8. P-values {\\textless}0.05 were considered statistically significant. Results: The quantification of JAK2 V617F was carried out in a total of 52 patient samples with both techniques. Of the 52 patients, 5 had a diagnosis of ET and 47 had PV. The average VAF of JAK2 V617F using dPCR was 14.1\\% and 48.2\\%, and 17.1\\% and 47.6\\% using NGS for ET patients and PV patients, respectively. The concordance of positivity for JAK2 V617F between the two methods was 100\\%. With dPCR, the average VAF of JAK2 V617F was 44.62\\% (range 2.7\\%-100\\%). With NGS, the average VAF of JAK2 V617F was 44.95\\% (range 2.5\\%-96.5\\%), with an average coverage/read depth {\\textgreater}3500 reads. At diagnosis, there was no difference in the mean VAF of JAK2 V617F determined using dPCR vs. NGS (44.62 vs. 44.95, p=0.792, paired Student t-test). There was an excellent correlation between the VAF of JAK2 V617F determined using dPCR vs. NGS (Pearson correlation coefficient 0.944, p{\\textless}0.001; Figure 1). Only 7 samples had a deviation {\\textgreater}10\\% in the VAF quantification. These determinations are indicated in orange in the graph and listed in the table . The cause of 2/7 deviations might have been a limited DNA volume/concentration available for dPCR. The high concordance of variant quantification by dPCR andNGS was maintained for JAK2 V617F with low VAFs (≤20\\%, mean 12.0\\% vs. 11.8\\%, respectively; p=0.840) and high VAFs (≥80\\%, mean 90.6\\% vs. 89.9\\%, respectively; p=0.858). Conclusions: Overall, excellent correlation was observed between the VAF of JAK2 V617F obtained using dPCR and NGS, showing that NGS is a robust quantification method. However, 7 samples had a difference {\\textgreater}10\\% VAF, with a deviation {\\textgreater}25\\% in 3 cases. Standardization of molecular techniques for JAK2 V617F quantification is important if the VAF is to be monitored during MPN patient follow-up as a biomarker for disease evolution and for response to treatment, with VAF reductions shown for pegylated interferon and ruxolitinib. DPCR might be better suited for follow-up quantification due to its higher sensitivity and lower price, while NGS at diagnosis, apart from detecting and quantifying JAK2 V617F at baseline, has the advantage of providing information on other gene mutations with prognostic value.},\n\turldate = {2024-01-23},\n\tjournal = {Blood},\n\tauthor = {Stuckey, Ruth and Santana, Guillermo and Florido, Yanira and Segura-Díaz, Adrián and Gómez-Casares, Maria Teresa and Bilbao-Sieyro, Cristina},\n\tmonth = nov,\n\tyear = {2023},\n\tkeywords = {MPN, MYS, Myelofibrosis, Myeloid Solution, Myeloproliferative Neoplasms, myeloproliferative neoplasms (MPN)},\n\tpages = {6396},\n}\n\n

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\n Introduction: JAK2 V617F is the most common mutation in the Philadelphia-negative myeloproliferative neoplasms (MPN), detected in 97% of polycythemia vera (PV), and approximately 55% of essential thrombocythemia (ET) and primary myelofibrosis (PMF) cases. According to the WHO, JAK2 V617F positivity is a major criteria for PV, ET or PMF diagnosis. But JAK2 V617F quantification at diagnosis could be useful since a high allelic frequency (or VAF) has been associated with increased symptom burden in PV, risk of thrombotic events in ET and progression in PMF. The current gold standard technique for JAK2 V617F quantification is allele-specific quantitative PCR (qPCR). However, digital PCR (dPCR) is increasingly being employed since it permits absolute quantification of JAK2 V617F without the need for a standard curve. QPCR vs. dPCR comparisons have shown high conformance between the two methods. Moreover, next-generation sequencing technologies (NGS) are increasingly used for MPN diagnosis. The aim of this study was to evaluate the concordance between dPCR and NGS for JAK2 V617F quantification at diagnosis. Methods: JAK2 V617F was quantified in the same sample of genomic DNA, extracted from total leukocytes from peripheral blood or bone marrow at diagnosis, by digital PCR (dPCR) and by NGS. The Absolute Q™ Liquid Biopsy dPCR Assay (JAK2 12600) was used in the QuantStudio™ Absolute Q™ Digital PCR System (Applied Biosystems) with 25 ng DNA. This assay quantifies the number of JAK2 WT-VIC and JAK2 V617F-FAM positive signals in 20000 partitions, determined as copies JAK2 V617F/µl input sample, and expressed as percentage VAF, with a limit of detection of 0.1%. NGS was performed with the MiSeq (Illumina) platform and the targeted 30-gene panel Myeloid Solution™ (SOPHiA GENETICS) using 200 ng DNA. VAF was determined as the number of variant reads divided by the number of total reads (reported as a percentage), with a limit of detection of 2.5%. Statistical analyses were performed using R-commander version 2.8. P-values \\textless0.05 were considered statistically significant. Results: The quantification of JAK2 V617F was carried out in a total of 52 patient samples with both techniques. Of the 52 patients, 5 had a diagnosis of ET and 47 had PV. The average VAF of JAK2 V617F using dPCR was 14.1% and 48.2%, and 17.1% and 47.6% using NGS for ET patients and PV patients, respectively. The concordance of positivity for JAK2 V617F between the two methods was 100%. With dPCR, the average VAF of JAK2 V617F was 44.62% (range 2.7%-100%). With NGS, the average VAF of JAK2 V617F was 44.95% (range 2.5%-96.5%), with an average coverage/read depth \\textgreater3500 reads. At diagnosis, there was no difference in the mean VAF of JAK2 V617F determined using dPCR vs. NGS (44.62 vs. 44.95, p=0.792, paired Student t-test). There was an excellent correlation between the VAF of JAK2 V617F determined using dPCR vs. NGS (Pearson correlation coefficient 0.944, p\\textless0.001; Figure 1). Only 7 samples had a deviation \\textgreater10% in the VAF quantification. These determinations are indicated in orange in the graph and listed in the table . The cause of 2/7 deviations might have been a limited DNA volume/concentration available for dPCR. The high concordance of variant quantification by dPCR andNGS was maintained for JAK2 V617F with low VAFs (≤20%, mean 12.0% vs. 11.8%, respectively; p=0.840) and high VAFs (≥80%, mean 90.6% vs. 89.9%, respectively; p=0.858). Conclusions: Overall, excellent correlation was observed between the VAF of JAK2 V617F obtained using dPCR and NGS, showing that NGS is a robust quantification method. However, 7 samples had a difference \\textgreater10% VAF, with a deviation \\textgreater25% in 3 cases. Standardization of molecular techniques for JAK2 V617F quantification is important if the VAF is to be monitored during MPN patient follow-up as a biomarker for disease evolution and for response to treatment, with VAF reductions shown for pegylated interferon and ruxolitinib. DPCR might be better suited for follow-up quantification due to its higher sensitivity and lower price, while NGS at diagnosis, apart from detecting and quantifying JAK2 V617F at baseline, has the advantage of providing information on other gene mutations with prognostic value.\n

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\n \n\n \n \n \n \n \n \n Clinical, Cytogenetic and Molecular Characterization of a 96 MDS and AML Cohort with TP53 Mutation.\n \n \n \n \n\n\n \n Duranjou, M.; Castoldi, C.; Alary, A. S.; Hicheri, Y.; Saillard, C.; Rouzaud, C.; Charbonnier, A.; Mohty, B.; D'Incan, E.; Rey, J.; Hospital, M. A.; Devillier, R.; Vey, N.; Gelsi-Boyer, V.; Lhoumeau, A.; Murati, A.; Golesi, F.; Mozziconacci, M. J.; Ittel, A.; and Garciaz, S.\n\n\n \n\n\n\n Blood, 142: 6483. November 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Clinical,$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{duranjou_clinical_2023,\n\tseries = {65th {ASH} {Annual} {Meeting} {Abstracts}},\n\ttitle = {Clinical, {Cytogenetic} and {Molecular} {Characterization} of a 96 {MDS} and {AML} {Cohort} with {TP53} {Mutation}},\n\tvolume = {142},\n\tissn = {0006-4971},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0006497123130801},\n\tdoi = {10.1182/blood-2023-186086},\n\tabstract = {Introduction The last European LeukamiaNet (ELN) recommendations (Döhner H. et al. Blood. 2022) and the International Consensus Classification (ICC, Hasserjian R.P. et al. Virchows Arch. 2023) described a new entity, called myelodysplastic syndrome (MDS)/ acute myeloid leukemia (AML) with TP53 mutation ( TP53mut), comprising high-risk MDS with an excess of bone marrow blasts cells (more than 10\\%) and a TP53 mutation (variant allele frequency VAF ≥ 10\\%). They suggested that MDS and AML represent a biologic continuum rather than two distinct diseases separated by a blast cutoff. Among teams who worked on that topic, T. Grob et al. ( Blood. 2022) studied the molecular characterization of high-risk AML and MDS with TP53mut and suggested that these two types of pathologies should be considered as a single entity, with no difference in molecular characteristics or survival. In this study, we describe the clinical, cytogenetic, and molecular characteristics of a cohort of 96 MDS and AMLs with TP53mut. Patients and methods We included all the patients with AML, MDS/AML, MDS with increased blasts (MDS-IB1) and MDS-low blast (MDS-LB) with at least one TP53mut (VAF ≥ 1\\%) received between Aug. 2020 and Dec. 2022 at the Institut Paoli-Calmettes (IPC, Marseille, France). Clinical and biological data were extracted retrospectively from the AML IPC database. Morphologic and cytogenetic data were analyzed by standard techniques. NGS was performed using a custom targeted panel of 60 genes (Custom Myeloid Lymphoid Solution, SOPHIA GENETICS). Results We registered 96 patients with a TP53 mutation (VAF ≥ 1\\%), divided into AML (n=60), MDS/AML (n=14), MDS-IB1 (n=12) and MDS-LB (n=10). Median age was 71 (range, 28-88). Thirty-eight patients had been treated for a prior solid malignancy and 26 patients had a history of myeloid malignancy. TP53mut was detected at diagnosis for 85 patients and at relapse or during follow-up for 12 patients (no NGS data available at diagnosis). We detected 142 mutations in the TP53 gene, mostly missense (73\\%) between exon 4 and exon 11 with a median VAF of 39\\% (Figure 1). We found 3 hotspots mutations in positions 273, 248 and 220 with respectively 9, 9 and 8 mutations. Biallelic status (presence of ≥ 2 mutations or a mutation + a deletion) was found in 66 patients (69\\%). Karyotypes were available for 95 patients. The karyotype was abnormal in 88\\% of cases, complex in 71\\% and unfavorable in 80\\% of cases according to ELN classification or Revised International Prognostic Scoring System (R-IPSS). Complete NGS analysis revealed at least one mutation in 59 of the other genes of the panel in 67 patients (70\\%), the most frequent being DNMT3A (22\\%), TET2 (17\\%), ASXL1 (13\\%) and PPM1D (11\\%) (Figure 2). In our cohort of TP53mut LB-MDS (n=10), we found that 9/10 patients had co-mutations in DNMT3A (n=4) , TET2 (n=6) and PPM1D (n=2) genes, 7/10 with biallelic status and 3/10 with complex karyotype. AML and MDS/AML patients with TP53mut detected at diagnosis (n=65) were treated with intensive chemotherapy (n=13), VEN-AZA (n=26), non-intensive therapy (n=14) or best supportive care (BSC, n=12). Seventeen patients were treated with allogeneic stem-cell transplantation (ASCT). With a median follow-up (FU) of 13 months, median overall survival (OS) of the whole cohort was 7 months (ranges, 1-41). Median OS in the AML and MDS/AML group was 6 months (ranges, 1-41). Patients treated with non-intensive approach had the longest median OS (15 months) compared to patients treated with intensive chemotherapy and VEN-based approaches (8 and 6 months, respectively) and patients treated with BSC (1 month, p=0.02). Patients with MDS-IB1 and MDS-LB had 11-months median OS (ranges, 1-28). The four patients treated with upfront ASCT were still alive at the last FU date and have an estimated median OS of 18.5 months (ranges, 6-26). Conclusion Our data confirm that MDS and AML with TP53 mutation are frequently associated with complex karyotypes and have a poor prognosis. nterestingly we identified mutations in PPM1D gene, involved in TP53 pathway, in 11\\% of cases. Patients with AML or MDS/AML treated with non-intensive approach seem to have the longest OS (15 months). Patients with MDS-IB1 or MDS-LB treated with upfront ASCT seem to have a prolonged OS (18.5 months). Clinical, functional and mechanistic studies are required to complete these findings.},\n\turldate = {2024-01-23},\n\tjournal = {Blood},\n\tauthor = {Duranjou, Marine and Castoldi, Cécile and Alary, Anne Sophie and Hicheri, Yosr and Saillard, Colombe and Rouzaud, Camille and Charbonnier, Aude and Mohty, Bilal and D'Incan, Evelyne and Rey, Jerome and Hospital, Marie Anne and Devillier, Raynier and Vey, Norbert and Gelsi-Boyer, Véronique and Lhoumeau, Anne-Catherine and Murati, Anne and Golesi, Florence and Mozziconacci, Marie Joelle and Ittel, Antoine and Garciaz, Sylvain},\n\tmonth = nov,\n\tyear = {2023},\n\tkeywords = {AML, Acute myeloid leukaemia, Custom Cancer Panel, Custom MYS, TP53},\n\tpages = {6483},\n}\n\n

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\n Introduction The last European LeukamiaNet (ELN) recommendations (Döhner H. et al. Blood. 2022) and the International Consensus Classification (ICC, Hasserjian R.P. et al. Virchows Arch. 2023) described a new entity, called myelodysplastic syndrome (MDS)/ acute myeloid leukemia (AML) with TP53 mutation ( TP53mut), comprising high-risk MDS with an excess of bone marrow blasts cells (more than 10%) and a TP53 mutation (variant allele frequency VAF ≥ 10%). They suggested that MDS and AML represent a biologic continuum rather than two distinct diseases separated by a blast cutoff. Among teams who worked on that topic, T. Grob et al. ( Blood. 2022) studied the molecular characterization of high-risk AML and MDS with TP53mut and suggested that these two types of pathologies should be considered as a single entity, with no difference in molecular characteristics or survival. In this study, we describe the clinical, cytogenetic, and molecular characteristics of a cohort of 96 MDS and AMLs with TP53mut. Patients and methods We included all the patients with AML, MDS/AML, MDS with increased blasts (MDS-IB1) and MDS-low blast (MDS-LB) with at least one TP53mut (VAF ≥ 1%) received between Aug. 2020 and Dec. 2022 at the Institut Paoli-Calmettes (IPC, Marseille, France). Clinical and biological data were extracted retrospectively from the AML IPC database. Morphologic and cytogenetic data were analyzed by standard techniques. NGS was performed using a custom targeted panel of 60 genes (Custom Myeloid Lymphoid Solution, SOPHIA GENETICS). Results We registered 96 patients with a TP53 mutation (VAF ≥ 1%), divided into AML (n=60), MDS/AML (n=14), MDS-IB1 (n=12) and MDS-LB (n=10). Median age was 71 (range, 28-88). Thirty-eight patients had been treated for a prior solid malignancy and 26 patients had a history of myeloid malignancy. TP53mut was detected at diagnosis for 85 patients and at relapse or during follow-up for 12 patients (no NGS data available at diagnosis). We detected 142 mutations in the TP53 gene, mostly missense (73%) between exon 4 and exon 11 with a median VAF of 39% (Figure 1). We found 3 hotspots mutations in positions 273, 248 and 220 with respectively 9, 9 and 8 mutations. Biallelic status (presence of ≥ 2 mutations or a mutation + a deletion) was found in 66 patients (69%). Karyotypes were available for 95 patients. The karyotype was abnormal in 88% of cases, complex in 71% and unfavorable in 80% of cases according to ELN classification or Revised International Prognostic Scoring System (R-IPSS). Complete NGS analysis revealed at least one mutation in 59 of the other genes of the panel in 67 patients (70%), the most frequent being DNMT3A (22%), TET2 (17%), ASXL1 (13%) and PPM1D (11%) (Figure 2). In our cohort of TP53mut LB-MDS (n=10), we found that 9/10 patients had co-mutations in DNMT3A (n=4) , TET2 (n=6) and PPM1D (n=2) genes, 7/10 with biallelic status and 3/10 with complex karyotype. AML and MDS/AML patients with TP53mut detected at diagnosis (n=65) were treated with intensive chemotherapy (n=13), VEN-AZA (n=26), non-intensive therapy (n=14) or best supportive care (BSC, n=12). Seventeen patients were treated with allogeneic stem-cell transplantation (ASCT). With a median follow-up (FU) of 13 months, median overall survival (OS) of the whole cohort was 7 months (ranges, 1-41). Median OS in the AML and MDS/AML group was 6 months (ranges, 1-41). Patients treated with non-intensive approach had the longest median OS (15 months) compared to patients treated with intensive chemotherapy and VEN-based approaches (8 and 6 months, respectively) and patients treated with BSC (1 month, p=0.02). Patients with MDS-IB1 and MDS-LB had 11-months median OS (ranges, 1-28). The four patients treated with upfront ASCT were still alive at the last FU date and have an estimated median OS of 18.5 months (ranges, 6-26). Conclusion Our data confirm that MDS and AML with TP53 mutation are frequently associated with complex karyotypes and have a poor prognosis. nterestingly we identified mutations in PPM1D gene, involved in TP53 pathway, in 11% of cases. Patients with AML or MDS/AML treated with non-intensive approach seem to have the longest OS (15 months). Patients with MDS-IB1 or MDS-LB treated with upfront ASCT seem to have a prolonged OS (18.5 months). Clinical, functional and mechanistic studies are required to complete these findings.\n

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\n \n\n \n \n \n \n \n \n Mutational Burden in High Risk Genes Do Not Affect Remission Rates and MRD Clearance in Elderly AML Patients Receiving CPX-351 Induction.\n \n \n \n \n\n\n \n Riva, C.; Minetto, P.; Carminati, E.; Chies, M.; Vernarecci, C.; Ferro, B.; Maio, E.; Zecchetti, G.; Frello, M.; Miglino, M.; Tedone, E.; Colombo, N.; Nurra, C.; Puglisi, F.; Cagnetta, A.; Cea, M.; Fugazza, G.; Lemoli, R. M.; and Guolo, F.\n\n\n \n\n\n\n Blood, 142: 6016. November 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Mutational$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{riva_mutational_2023,\n\tseries = {65th {ASH} {Annual} {Meeting} {Abstracts}},\n\ttitle = {Mutational {Burden} in {High} {Risk} {Genes} {Do} {Not} {Affect} {Remission} {Rates} and {MRD} {Clearance} in {Elderly} {AML} {Patients} {Receiving} {CPX}-351 {Induction}},\n\tvolume = {142},\n\tissn = {0006-4971},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0006497123126152},\n\tdoi = {10.1182/blood-2023-186555},\n\tabstract = {Background: CPX-351 has recently been approved for the treatment of patients diagnosed with Acute Myeloid Leukemia (AML) arising from a previous myelodisplastic syndrome (s-AML) or secondary to chemotherapy (t-AML) as per former WHO 2016 classification. Minimal residual disease (MRD) assessment is a strong prognostic factor for relapse and shorter survival in AML patients undergoing intensive induction chemotherapy. Recent studies explored the role of genomic profile of AML influencing clinical outcome. In particular, Papaemmanuil et al showed that mutations in critical genes such as TP53, ASXL1, SRSF2 and RUNX1 are independently associated with a worse prognosis; moreover, co-occurrence of different high-risk mutations are predictors of dismal outcome when conventional chemotherapy is administered. Adverse risk mutations are particularly frequent in s-AML and t-AML. As clinical trials evaluating the prognostic relevance of MRD in the context of different molecular subsets mainly involve younger patients affected by de novo AML and receiving conventional 3+7 chemotherapy, there is a lack of data to define the impact of specific mutations on MRD clearance and prognosis in elderly s- AML and t-AML patients receiving CPX-351 induction. Aims: The aim of this study was to evaluate the prognostic impact of recurrent genic mutations and mutational burden at diagnosis on CR probability, MRD clearance and prognosis in a cohort of elderly s-AML or t-AML patients treated with CPX-351 induction chemotherapy. Methods: The study included 67 elderly patients ({\\textgreater}60 year, median age 69, range 60-77) with a diagnosis of s-AML or t-AML according to WHO2016 classification, treated in our Center with CPX-351. Next generation sequencing (NGS) was performed using the Myeloid Solution panel by SOPHiA Genetics, encompassing 34 critical genes mutations. Sample have been processed on a Illumina MiSeq platform and the analysis performed with SOPHiA DDM® Software. MRD was analysed in all patients achieving complete remission (CR) with multicolour flow-cytometry, with a threshold of 0.1\\%. Results: AML patients were re-classified according to ELN 2022 risk score which was adverse, intermediate and favourable in 35, 29 and 3 patients, respectively. Median number of mutations for single patient (mutational burden) by NGS was 4 (range 2-9). Most frequent mutations involved: RUNX1 (44\\%), ASXL1 (37\\%), TP53 (33\\%), IDH1 (18\\%), IDH2 (14\\%), DNMT3A (14\\%), TET2 (8\\%). Four patients died before response assessment, mainly due to infections. Fifty-four patients (81\\%) achieved complete remission (CR) after first induction cycle; MRD evaluation was negative in 28/54 responding patients (52\\%). Univariate and multivariate analysis showed that factors traditionally associated with poor outcome such as ELN risk group, leukocytosis at diagnosis or previous treatment with hypomethylating agents did not affect the probability of CR rate and MRD negativity. Interestingly, having any high risk mutation, the combination of ≥2 high risk mutations or high mutational burden (having ≥ 4) did not affect CR probability and MRD negativity rate both in univariate and multivariate analysis. After cycle 2, the cumulative CR rate was 56/67 (84\\%), with 33/56 (59\\%) responding patients obtaining MFC MRD negativity. After a median follow up of 36 months (CI 95\\%; 22.4 -48.5 months), median OS was 19 months (CI 95\\% 13-24), whereas 2 year OS was 24\\%. Multivariate OS analysis revealed that negative MRD was the strongest independent predictor of longer survival (p{\\textless}0.05). Notably, OS was not affected by mutational burden (29.2\\% and 27.6\\% for patients with less or more than 4 mutations, respectively, p=n.s, Fig.1). In landmark analysis, patients achieving CR and proceeding to allogeneic stem cell transplantation consolidation (HSCT) within 3 months from CR (N=13) had a significantly better outcome if compared to CR patients who did not receive HSCT or proceeded to transplant later (N= 41, 2-year OS: 84.6\\% and 31.7, respectively, p{\\textless}0.03, Fig. 2). Conclusion : CPX-351 is able to induce good quality remission with high CR rate and MRD negativity, regardless of mutational burden, allowing a high number of elderly AML patients to undergo to HSCT. MRD evaluation has proven to be a strong prognostic tool also in the setting of elderly s-AML and t-AML patients receiving CPX-351. The prognostic value of high risk mutation seems to be less relevant in CPX-351 treated patients.},\n\turldate = {2024-01-23},\n\tjournal = {Blood},\n\tauthor = {Riva, Carola and Minetto, Paola and Carminati, Enrico and Chies, Maria and Vernarecci, Chiara and Ferro, Beatrice and Maio, Elena and Zecchetti, Giada and Frello, Michela and Miglino, Maurizio and Tedone, Elisabetta and Colombo, Nicoletta and Nurra, Clara and Puglisi, Francesco and Cagnetta, Antonia and Cea, Michele and Fugazza, Giuseppina and Lemoli, Roberto Massimo and Guolo, Fabio},\n\tmonth = nov,\n\tyear = {2023},\n\tkeywords = {AML, Acute myeloid leukaemia, MYS},\n\tpages = {6016},\n}\n\n

\n\n\n

\n Background: CPX-351 has recently been approved for the treatment of patients diagnosed with Acute Myeloid Leukemia (AML) arising from a previous myelodisplastic syndrome (s-AML) or secondary to chemotherapy (t-AML) as per former WHO 2016 classification. Minimal residual disease (MRD) assessment is a strong prognostic factor for relapse and shorter survival in AML patients undergoing intensive induction chemotherapy. Recent studies explored the role of genomic profile of AML influencing clinical outcome. In particular, Papaemmanuil et al showed that mutations in critical genes such as TP53, ASXL1, SRSF2 and RUNX1 are independently associated with a worse prognosis; moreover, co-occurrence of different high-risk mutations are predictors of dismal outcome when conventional chemotherapy is administered. Adverse risk mutations are particularly frequent in s-AML and t-AML. As clinical trials evaluating the prognostic relevance of MRD in the context of different molecular subsets mainly involve younger patients affected by de novo AML and receiving conventional 3+7 chemotherapy, there is a lack of data to define the impact of specific mutations on MRD clearance and prognosis in elderly s- AML and t-AML patients receiving CPX-351 induction. Aims: The aim of this study was to evaluate the prognostic impact of recurrent genic mutations and mutational burden at diagnosis on CR probability, MRD clearance and prognosis in a cohort of elderly s-AML or t-AML patients treated with CPX-351 induction chemotherapy. Methods: The study included 67 elderly patients (\\textgreater60 year, median age 69, range 60-77) with a diagnosis of s-AML or t-AML according to WHO2016 classification, treated in our Center with CPX-351. Next generation sequencing (NGS) was performed using the Myeloid Solution panel by SOPHiA Genetics, encompassing 34 critical genes mutations. Sample have been processed on a Illumina MiSeq platform and the analysis performed with SOPHiA DDM® Software. MRD was analysed in all patients achieving complete remission (CR) with multicolour flow-cytometry, with a threshold of 0.1%. Results: AML patients were re-classified according to ELN 2022 risk score which was adverse, intermediate and favourable in 35, 29 and 3 patients, respectively. Median number of mutations for single patient (mutational burden) by NGS was 4 (range 2-9). Most frequent mutations involved: RUNX1 (44%), ASXL1 (37%), TP53 (33%), IDH1 (18%), IDH2 (14%), DNMT3A (14%), TET2 (8%). Four patients died before response assessment, mainly due to infections. Fifty-four patients (81%) achieved complete remission (CR) after first induction cycle; MRD evaluation was negative in 28/54 responding patients (52%). Univariate and multivariate analysis showed that factors traditionally associated with poor outcome such as ELN risk group, leukocytosis at diagnosis or previous treatment with hypomethylating agents did not affect the probability of CR rate and MRD negativity. Interestingly, having any high risk mutation, the combination of ≥2 high risk mutations or high mutational burden (having ≥ 4) did not affect CR probability and MRD negativity rate both in univariate and multivariate analysis. After cycle 2, the cumulative CR rate was 56/67 (84%), with 33/56 (59%) responding patients obtaining MFC MRD negativity. After a median follow up of 36 months (CI 95%; 22.4 -48.5 months), median OS was 19 months (CI 95% 13-24), whereas 2 year OS was 24%. Multivariate OS analysis revealed that negative MRD was the strongest independent predictor of longer survival (p\\textless0.05). Notably, OS was not affected by mutational burden (29.2% and 27.6% for patients with less or more than 4 mutations, respectively, p=n.s, Fig.1). In landmark analysis, patients achieving CR and proceeding to allogeneic stem cell transplantation consolidation (HSCT) within 3 months from CR (N=13) had a significantly better outcome if compared to CR patients who did not receive HSCT or proceeded to transplant later (N= 41, 2-year OS: 84.6% and 31.7, respectively, p\\textless0.03, Fig. 2). Conclusion : CPX-351 is able to induce good quality remission with high CR rate and MRD negativity, regardless of mutational burden, allowing a high number of elderly AML patients to undergo to HSCT. MRD evaluation has proven to be a strong prognostic tool also in the setting of elderly s-AML and t-AML patients receiving CPX-351. The prognostic value of high risk mutation seems to be less relevant in CPX-351 treated patients.\n

\n\n\n

\n \n\n \n \n \n \n \n \n Proteogenomics Coupled with Ex Vivo Profiling for Therapeutic Targeting in AML.\n \n \n \n \n\n\n \n Murray, H. C; Enjeti, A. K; Samaraweera, S.; Brzozowski, J. S; Miller, K.; D'Andrea, R. J; and Verrills, N. M\n\n\n \n\n\n\n Blood, 142: 4300. November 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Proteogenomics$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{murray_proteogenomics_2023,\n\tseries = {65th {ASH} {Annual} {Meeting} {Abstracts}},\n\ttitle = {Proteogenomics {Coupled} with {Ex} {Vivo} {Profiling} for {Therapeutic} {Targeting} in {AML}},\n\tvolume = {142},\n\tissn = {0006-4971},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0006497123109013},\n\tdoi = {10.1182/blood-2023-191314},\n\tabstract = {AML is the most common acute leukaemia in adults and incidence is on the rise, partly due to population ageing. Despite the emergence of new targeted therapies for AML patients, survival rates remain dismal ({\\textasciitilde}27\\% at 5 years). Current challenges include the rapid development of resistance and the inability to predict which therapy is optimal for each patient, especially for those without ‘actionable’ mutations. These challenges are compounded by the lack of complete testing platforms for capturing critical patient-specific molecular profiles beyond somatic mutations, such as changes in the proteome and phosphoproteome. Due to the heterogeneous nature of AML, individualised screening and personalised treatment plans are likely required to improve treatment and survival outcomes for AML patients. By combining genetic profiling, phosphoproteomic and proteomic analysis, we have developed a pipeline for profiling AML patient samples. Using this pipeline, we have identified novel therapies for different leukaemia subtypes ( Leukemia, 2021). In this study, we have integrated genomic, proteomic, and phosphoproteomic profiling together with ex vivo drug sensitivity profiling for a functional read-out of drug sensitivity or resistance, to identify optimal therapeutic regimes for individual AML patients. Ex vivo drug sensitivity profiling has been performed on 71 patients. Genomic profiling was performed using the SOPHiA Genetics Myeloid Panel. The mutation frequency identified was similar to previous reports ( TCGA, N Engl J Med 2013). The drug screen panel included AML standard of care treatments (e.g., cytarabine, midostaurin) as well as investigational agents. Cell survival was measured at 24 hours using an ATPlite assay or Annexin V staining. Results identified both known and novel associations with mutation subgroups. Consistent with previous reports ( Jawhar, Blood 2017), IDH2 mutations were associated with reduced sensitivity to midostaurin (p=0.0039). Samples with NPM1 mutation were significantly more sensitive to Aurora kinase/CDK inhibitor JNJ7706621 compared to NPM1 wildtype (p=0.0007). This association also held true in the BeatAML cohort (Vizome, p{\\textless}0.0001). NPM1 has documented roles in cell cycle regulation, and these results suggest that mutant NPM1 may sensitise to cell cycle targeted therapies. Multi-omic analyses of 23 intermediate/high risk patients, 9 of which had no actionable mutations, identified further drug vulnerabilities, with {\\textgreater}2 therapies identified for each patient. Validation of this approach is exemplified by individual case studies where our profiling platform correlates with clinical outcome. In the first case, the patient presented with a KRAS mutation, predictive of resistance to midostaurin. Proteomic profiling identified low expression of BCL2, predictive of resistance to venetoclax. Phosphoproteomic profiling however identified activation of DNA repair and CDK proteins, suggesting sensitivity to DNA repair and CDK inhibitors. Ex vivo drug sensitivity profiling of the patient blasts identified resistance to midostaurin and venetoclax, but sensitivity to PARP and CDK inhibitors. Concurrently, the patient received a combination of standard chemotherapy and targeted therapy (cytarabine, midostaurin, venetoclax) and was primary refractory to treatment. In a second case, proteogenomics and ex vivo screening predicted sensitivity to midostaurin and venetoclax. The patient received cytarabine, midostaurin, and venetoclax therapy and achieved remission. In our third case study, ex vivo screening predicted sensitivity to standard of care agents (cytarabine, midostaurin, venetoclax). While the patient achieved remission with standard of care chemotherapy, they subsequently relapsed. At relapse, ex vivo screening identified reduced sensitivity to cytarabine but a high level of venetoclax sensitivity. The patient was placed on FLAG with venetoclax and was bridged to transplant. Therefore, our approach can predict treatment sensitivities and resistance to standard of care therapies, and may also identify alternative clinically available therapies. The results of these and further case studies will be presented at the meeting.},\n\turldate = {2024-01-23},\n\tjournal = {Blood},\n\tauthor = {Murray, Heather C and Enjeti, Anoop K and Samaraweera, Saumya and Brzozowski, Joshua S and Miller, Kasey and D'Andrea, Richard J and Verrills, Nicole M},\n\tmonth = nov,\n\tyear = {2023},\n\tkeywords = {AML, Acute myeloid leukaemia, MYS, Myeloid Solution},\n\tpages = {4300},\n}\n\n

\n\n\n

\n AML is the most common acute leukaemia in adults and incidence is on the rise, partly due to population ageing. Despite the emergence of new targeted therapies for AML patients, survival rates remain dismal (~27% at 5 years). Current challenges include the rapid development of resistance and the inability to predict which therapy is optimal for each patient, especially for those without ‘actionable’ mutations. These challenges are compounded by the lack of complete testing platforms for capturing critical patient-specific molecular profiles beyond somatic mutations, such as changes in the proteome and phosphoproteome. Due to the heterogeneous nature of AML, individualised screening and personalised treatment plans are likely required to improve treatment and survival outcomes for AML patients. By combining genetic profiling, phosphoproteomic and proteomic analysis, we have developed a pipeline for profiling AML patient samples. Using this pipeline, we have identified novel therapies for different leukaemia subtypes ( Leukemia, 2021). In this study, we have integrated genomic, proteomic, and phosphoproteomic profiling together with ex vivo drug sensitivity profiling for a functional read-out of drug sensitivity or resistance, to identify optimal therapeutic regimes for individual AML patients. Ex vivo drug sensitivity profiling has been performed on 71 patients. Genomic profiling was performed using the SOPHiA Genetics Myeloid Panel. The mutation frequency identified was similar to previous reports ( TCGA, N Engl J Med 2013). The drug screen panel included AML standard of care treatments (e.g., cytarabine, midostaurin) as well as investigational agents. Cell survival was measured at 24 hours using an ATPlite assay or Annexin V staining. Results identified both known and novel associations with mutation subgroups. Consistent with previous reports ( Jawhar, Blood 2017), IDH2 mutations were associated with reduced sensitivity to midostaurin (p=0.0039). Samples with NPM1 mutation were significantly more sensitive to Aurora kinase/CDK inhibitor JNJ7706621 compared to NPM1 wildtype (p=0.0007). This association also held true in the BeatAML cohort (Vizome, p\\textless0.0001). NPM1 has documented roles in cell cycle regulation, and these results suggest that mutant NPM1 may sensitise to cell cycle targeted therapies. Multi-omic analyses of 23 intermediate/high risk patients, 9 of which had no actionable mutations, identified further drug vulnerabilities, with \\textgreater2 therapies identified for each patient. Validation of this approach is exemplified by individual case studies where our profiling platform correlates with clinical outcome. In the first case, the patient presented with a KRAS mutation, predictive of resistance to midostaurin. Proteomic profiling identified low expression of BCL2, predictive of resistance to venetoclax. Phosphoproteomic profiling however identified activation of DNA repair and CDK proteins, suggesting sensitivity to DNA repair and CDK inhibitors. Ex vivo drug sensitivity profiling of the patient blasts identified resistance to midostaurin and venetoclax, but sensitivity to PARP and CDK inhibitors. Concurrently, the patient received a combination of standard chemotherapy and targeted therapy (cytarabine, midostaurin, venetoclax) and was primary refractory to treatment. In a second case, proteogenomics and ex vivo screening predicted sensitivity to midostaurin and venetoclax. The patient received cytarabine, midostaurin, and venetoclax therapy and achieved remission. In our third case study, ex vivo screening predicted sensitivity to standard of care agents (cytarabine, midostaurin, venetoclax). While the patient achieved remission with standard of care chemotherapy, they subsequently relapsed. At relapse, ex vivo screening identified reduced sensitivity to cytarabine but a high level of venetoclax sensitivity. The patient was placed on FLAG with venetoclax and was bridged to transplant. Therefore, our approach can predict treatment sensitivities and resistance to standard of care therapies, and may also identify alternative clinically available therapies. The results of these and further case studies will be presented at the meeting.\n

\n\n\n

\n \n\n \n \n \n \n \n \n Lysinuric protein intolerance caused by a homozygous SLC7A7 deletion and presented with hyperferritinemia and osteoporosis in two siblings.\n \n \n \n \n\n\n \n Kalay, I.; Aykut, H.; Caliskan, Z.; Yigit, G.; and Wollnik, B.\n\n\n \n\n\n\n Molecular Genetics and Metabolism Reports, 37: 101022. November 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Lysinuric$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{kalay_lysinuric_2023,\n\ttitle = {Lysinuric protein intolerance caused by a homozygous {SLC7A7} deletion and presented with hyperferritinemia and osteoporosis in two siblings},\n\tvolume = {37},\n\tissn = {2214-4269},\n\turl = {https://www.sciencedirect.com/science/article/pii/S221442692300068X},\n\tdoi = {10.1016/j.ymgmr.2023.101022},\n\tabstract = {Lysinuric protein intolerance (LPI) is a rare, inherited aminoaciduria caused by biallelic pathogenic variants in the amino acid transporter gene SLC7A7 (OMIM *603593). Individuals with LPI show extreme variability in their clinical presentation, and LPI is included in the differential diagnosis of several disorders such as urea cycle disorders, lysosomal storage diseases, malabsorption diseases, autoimmune disorders, hemochromatosis, and osteoporosis. The phenotypic variability of LPI and the lack of a specific clinical presentation have caused various misdiagnoses. Here, we report two siblings diagnosed in their 4th decade of life with LPI, manifesting rare hyperferritinemia. Additionally, they presented with short stature, multiple bone fractures due to osteoporosis, and they showed an aversion to protein-rich food. Using a combination of exome sequencing, microarray analysis and qPCR, we identified a novel homozygous deletion in SLC7A7 encompassing exons 3 to 10, which is predicted to lead to disruption of SLC7A7 function. This is the first report of lysinuric protein intolerance in a Turkish family associated with this so far unknown deletion in SLC7A7.},\n\turldate = {2024-01-23},\n\tjournal = {Molecular Genetics and Metabolism Reports},\n\tauthor = {Kalay, Irem and Aykut, Hüseyin and Caliskan, Zuhal and Yigit, Gökhan and Wollnik, Bernd},\n\tmonth = nov,\n\tyear = {2023},\n\tkeywords = {CES, CNV, Clinical Exome Solution, DDM, Hyperferritinemia, Lysinuric protein intolerance (LPI), Multiple bone fractures, clinical exome sequencing (CES), copy number variation (CNV), deletion},\n\tpages = {101022},\n}\n\n

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\n \n\n \n \n \n \n \n \n Yield of exome sequencing in patients with developmental and epileptic encephalopathies and inconclusive targeted gene panel.\n \n \n \n \n\n\n \n Sedlackova, L.; Sterbova, K.; Vlckova, M.; Seeman, P.; Zarubova, J.; Marusic, P.; Krsek, P.; Krijtova, H.; Musilova, A.; and Lassuthova, P.\n\n\n \n\n\n\n European Journal of Paediatric Neurology, 48: 17–29. November 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Yield$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{sedlackova_yield_2023,\n\ttitle = {Yield of exome sequencing in patients with developmental and epileptic encephalopathies and inconclusive targeted gene panel},\n\tvolume = {48},\n\tissn = {1090-3798},\n\turl = {https://www.sciencedirect.com/science/article/pii/S1090379823001617},\n\tdoi = {10.1016/j.ejpn.2023.10.006},\n\tabstract = {Objective\nDevelopmental and epileptic encephalopathies (DEEs) are a group of severe, early-onset epilepsies characterised by refractory seizures, developmental delay, or regression and generally poor prognosis. DEE are now known to have an identifiable molecular genetic basis and are usually examined using a gene panel. However, for many patients, the genetic cause has still not been identified. The aims of this study were to identify causal variants for DEE in patients for whom the previous examination with a gene panel did not determine their genetic diagnosis. It also aims for a detailed description and broadening of the phenotypic spectrum of several rare DEEs.\nMethods\nIn the last five years (2015–2020), 141 patients from all over the Czech Republic were referred to our department for genetic testing in association with their diagnosis of epilepsy. All patients underwent custom-designed gene panel testing prior to enrolment into the study, and their results were inconclusive. We opted for whole exome sequencing (WES) to identify the cause of their disorder. If a causal or potentially causal variant was identified, we performed a detailed clinical evaluation and phenotype-genotype correlation study to better describe the specific rare subtypes.\nResults\nExplanatory causative variants were detected in 20 patients (14\\%), likely pathogenic variants that explain the epilepsy in 5 patients (3.5\\%) and likely pathogenic variants that do not fully explain the epilepsy in 11 patients (7.5\\%), and variants in candidate genes in 4 patients (3\\%). Variants were mostly de novo 29/40 (72.5\\%).\nSignificance\nWES enables us to identify the cause of the disease in additional patients, even after gene panel testing. It is very important to perform a WES in DEE patients as soon as possible, since it will spare the patients and their families many years of a diagnostic odyssey. In particular, patients with rare epilepsies might significantly benefit from this approach, and we propose using WES as a new standard in the diagnosis of DEE instead of targeted gene panel testing.},\n\turldate = {2024-01-23},\n\tjournal = {European Journal of Paediatric Neurology},\n\tauthor = {Sedlackova, Lucie and Sterbova, Katalin and Vlckova, Marketa and Seeman, Pavel and Zarubova, Jana and Marusic, Petr and Krsek, Pavel and Krijtova, Hana and Musilova, Alena and Lassuthova, Petra},\n\tmonth = nov,\n\tyear = {2023},\n\tkeywords = {Alamut, Alamut Visual Plus, Alamut Visual Plus v1.6.1, Developmental and epileptic encephalopathies (DEE), Exome sequencing, Gene panel},\n\tpages = {17--29},\n}\n\n

\n\n\n

\n Objective Developmental and epileptic encephalopathies (DEEs) are a group of severe, early-onset epilepsies characterised by refractory seizures, developmental delay, or regression and generally poor prognosis. DEE are now known to have an identifiable molecular genetic basis and are usually examined using a gene panel. However, for many patients, the genetic cause has still not been identified. The aims of this study were to identify causal variants for DEE in patients for whom the previous examination with a gene panel did not determine their genetic diagnosis. It also aims for a detailed description and broadening of the phenotypic spectrum of several rare DEEs. Methods In the last five years (2015–2020), 141 patients from all over the Czech Republic were referred to our department for genetic testing in association with their diagnosis of epilepsy. All patients underwent custom-designed gene panel testing prior to enrolment into the study, and their results were inconclusive. We opted for whole exome sequencing (WES) to identify the cause of their disorder. If a causal or potentially causal variant was identified, we performed a detailed clinical evaluation and phenotype-genotype correlation study to better describe the specific rare subtypes. Results Explanatory causative variants were detected in 20 patients (14%), likely pathogenic variants that explain the epilepsy in 5 patients (3.5%) and likely pathogenic variants that do not fully explain the epilepsy in 11 patients (7.5%), and variants in candidate genes in 4 patients (3%). Variants were mostly de novo 29/40 (72.5%). Significance WES enables us to identify the cause of the disease in additional patients, even after gene panel testing. It is very important to perform a WES in DEE patients as soon as possible, since it will spare the patients and their families many years of a diagnostic odyssey. In particular, patients with rare epilepsies might significantly benefit from this approach, and we propose using WES as a new standard in the diagnosis of DEE instead of targeted gene panel testing.\n

\n\n\n

\n \n\n \n \n \n \n \n \n Improving diagnostic precision in primary ovarian insufficiency using comprehensive genetic and autoantibody testing.\n \n \n \n \n\n\n \n Vogt, E. C.; Bratland, E.; Berland, S.; Berentsen, R.; Lund, A.; Björnsdottir, S.; Husebye, E.; and Øksnes, M.\n\n\n \n\n\n\n Human Reproduction, 39(1): 177–189. November 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Improving$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{vogt_improving_2023,\n\ttitle = {Improving diagnostic precision in primary ovarian insufficiency using comprehensive genetic and autoantibody testing},\n\tvolume = {39},\n\tissn = {1460-2350},\n\turl = {https://doi.org/10.1093/humrep/dead233},\n\tdoi = {10.1093/humrep/dead233},\n\tabstract = {Is it possible to find the cause of primary ovarian insufficiency (POI) in more women by extensive screening?Adding next generation sequencing techniques including a POI-associated gene panel, extended whole exome sequencing data, as well as specific autoantibody assays to the recommended diagnostic investigations increased the determination of a potential etiological diagnosis of POI from 11\\% to 41\\%.POI affects ∼1\\% of women. Clinical presentations and pathogenic mechanisms are heterogeneous and include genetic, autoimmune, and environmental factors, but the underlying etiology remains unknown in the majority of cases.Prospective cross-sectional study of 100 women with newly diagnosed POI of unknown cause consecutively referred to Haukeland University Hospital, Bergen, Norway, January 2019 to December 2021.In addition to standard recommended diagnostic investigations including screening for chromosomal anomalies and premutations in the fragile X mental retardation 1 gene (FMR1) we used whole exome sequencing, including targeted analysis of 103 ovarian-related genes, and assays of autoantibodies against steroid cell antigens.We identified chromosomal aberrations in 8\\%, FMR1 premutations in 3\\%, genetic variants related to POI in 16\\%, and autoimmune POI in 3\\%. Furthermore in 11\\% we identified POI associated genetic Variants of unknown signifcance (VUS). A homozygous pathogenic variant in the ZSWIM7 gene (NM\\_001042697.2) was found in two women, corroborating this as a novel cause of monogenic POI. No associations between phenotypes and genotypes were found.Use of candidate genetic and autoimmune markers limit the possibility to discover new markers. To further investigate the genetic variants, family studies would have been useful. We found a relatively high proportion of genetic variants in women from Africa and lack of genetic diversity in the genomic databases can impact diagnostic accuracy.Since no specific clinical or biochemical markers predicted the underlying cause of POI discussion of which tests should be part of diagnostic screening in clinical practice remains open. New technology has altered the availability and effectiveness of genetic testing, and cost-effectiveness analyses are required to aid sustainable diagnostics.The study was supported by grants and fellowships from Stiftelsen Kristian Gerhard Jebsen, the Novonordisk Foundation, the Norwegian Research Council, University of Bergen, and the Regional Health Authorities of Western Norway. The authors declare no conflict of interest.NCT04082169},\n\tnumber = {1},\n\turldate = {2024-01-23},\n\tjournal = {Human Reproduction},\n\tauthor = {Vogt, Elinor Chelsom and Bratland, Eirik and Berland, Siren and Berentsen, Ragnhild and Lund, Agnethe and Björnsdottir, Sigridur and Husebye, Eystein and Øksnes, Marianne},\n\tmonth = nov,\n\tyear = {2023},\n\tkeywords = {Alamut Visual, FMR1, Primary ovarian insufficiency, VUS},\n\tpages = {177--189},\n}\n\n

\n\n\n

\n Is it possible to find the cause of primary ovarian insufficiency (POI) in more women by extensive screening?Adding next generation sequencing techniques including a POI-associated gene panel, extended whole exome sequencing data, as well as specific autoantibody assays to the recommended diagnostic investigations increased the determination of a potential etiological diagnosis of POI from 11% to 41%.POI affects ∼1% of women. Clinical presentations and pathogenic mechanisms are heterogeneous and include genetic, autoimmune, and environmental factors, but the underlying etiology remains unknown in the majority of cases.Prospective cross-sectional study of 100 women with newly diagnosed POI of unknown cause consecutively referred to Haukeland University Hospital, Bergen, Norway, January 2019 to December 2021.In addition to standard recommended diagnostic investigations including screening for chromosomal anomalies and premutations in the fragile X mental retardation 1 gene (FMR1) we used whole exome sequencing, including targeted analysis of 103 ovarian-related genes, and assays of autoantibodies against steroid cell antigens.We identified chromosomal aberrations in 8%, FMR1 premutations in 3%, genetic variants related to POI in 16%, and autoimmune POI in 3%. Furthermore in 11% we identified POI associated genetic Variants of unknown signifcance (VUS). A homozygous pathogenic variant in the ZSWIM7 gene (NM_001042697.2) was found in two women, corroborating this as a novel cause of monogenic POI. No associations between phenotypes and genotypes were found.Use of candidate genetic and autoimmune markers limit the possibility to discover new markers. To further investigate the genetic variants, family studies would have been useful. We found a relatively high proportion of genetic variants in women from Africa and lack of genetic diversity in the genomic databases can impact diagnostic accuracy.Since no specific clinical or biochemical markers predicted the underlying cause of POI discussion of which tests should be part of diagnostic screening in clinical practice remains open. New technology has altered the availability and effectiveness of genetic testing, and cost-effectiveness analyses are required to aid sustainable diagnostics.The study was supported by grants and fellowships from Stiftelsen Kristian Gerhard Jebsen, the Novonordisk Foundation, the Norwegian Research Council, University of Bergen, and the Regional Health Authorities of Western Norway. The authors declare no conflict of interest.NCT04082169\n

\n\n\n

\n \n\n \n \n \n \n \n \n Prevalence of BRCA1 and BRCA2 germline variants in an unselected pancreatic cancer patient cohort in Pakistan.\n \n \n \n \n\n\n \n Muhammad, N.; Azeem, A.; Arif, S.; Naeemi, H.; Masood, I.; Hassan, U.; Ijaz, B.; Hanif, F.; Syed, A. A.; Yusuf, M. A.; and Rashid, M. U.\n\n\n \n\n\n\n Hereditary Cancer in Clinical Practice, 21(1): 22. November 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Prevalence$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{muhammad_prevalence_2023,\n\ttitle = {Prevalence of {BRCA1} and {BRCA2} germline variants in an unselected pancreatic cancer patient cohort in {Pakistan}},\n\tvolume = {21},\n\tissn = {1897-4287},\n\turl = {https://doi.org/10.1186/s13053-023-00269-x},\n\tdoi = {10.1186/s13053-023-00269-x},\n\tabstract = {BRCA1 and BRCA2 (BRCA1/2) are the most frequently investigated genes among Caucasian pancreatic cancer patients, whereas limited reports are available among Asians. We aimed to investigate the prevalence of BRCA1/2 germline variants in Pakistani pancreatic cancer patients.},\n\tnumber = {1},\n\turldate = {2024-01-23},\n\tjournal = {Hereditary Cancer in Clinical Practice},\n\tauthor = {Muhammad, Noor and Azeem, Ayesha and Arif, Shumaila and Naeemi, Humaira and Masood, Iqra and Hassan, Usman and Ijaz, Bushra and Hanif, Faisal and Syed, Aamir Ali and Yusuf, Muhammed Aasim and Rashid, Muhammad Usman},\n\tmonth = nov,\n\tyear = {2023},\n\tkeywords = {Alamut, Alamut Visual Plus, Alamut Visual Plus v.1.2, BRCA1, BRCA2, Germline variants, Pakistan, Pancreatic cancer},\n\tpages = {22},\n}\n\n

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\n \n\n \n \n \n \n \n \n In-depth molecular analysis of lymphomas with lymphoplasmacytic differentiation may provide more precise diagnosis and rational treatment allocation.\n \n \n \n \n\n\n \n Brunner, A.; Thalhammer-Thurner, G. C.; Willenbacher, W.; Haun, M.; Zelger, B. G.; and Willenbacher, E.\n\n\n \n\n\n\n Annals of Hematology, 103(2): 553–563. November 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"In-depth$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{brunner_-depth_2023,\n\ttitle = {In-depth molecular analysis of lymphomas with lymphoplasmacytic differentiation may provide more precise diagnosis and rational treatment allocation},\n\tvolume = {103},\n\tissn = {1432-0584},\n\turl = {https://doi.org/10.1007/s00277-023-05531-9},\n\tdoi = {10.1007/s00277-023-05531-9},\n\tabstract = {We performed a molecular analysis of formalin-fixed paraffin embedded and decalcified bone marrow trephine biopsies of 41 patients with a B-cell disorder with lymphoplasmacytic differentiation to enable a more precise diagnosis and to describe potentially prognostic and therapeutic relevant mutations. Analysis was performed with a commercially available next-generation sequencing (NGS) lymphoma panel (Lymphoma Solution, SophiaGenetics). Results were correlated with clinical and pathological parameters. Our group covered a spectrum of B-cell disorders with plasmacytic differentiation ranging from Waldenstroem’s macroglobulinemia (WM), to small-B-cell lymphomas with plasmacytic differentiation (SBCL-PC) to IgM myeloma (MM). The most helpful diagnostic criteria included morphology and immuno-phenotype as a prerequisite for the interpretation of molecular analysis. MYD88 mutation was present in nearly all WM, but also in 50\\% of SBCL-PCs, while MM were consistently negative. Driver mutations, such as TP53, were already detectable early in the course of the respective diseases indicating a higher risk of progression, transformation, and reduced progression-free survival. In addition, we report on a novel BIRC3 frameshift mutation in one case of a progressive WM. Our data indicate that patients with LPL/WM might benefit from thorough pathological work-up and detailed molecular analysis in terms of precise diagnosis and targeted treatment allocation.},\n\tlanguage = {en},\n\tnumber = {2},\n\turldate = {2024-01-23},\n\tjournal = {Annals of Hematology},\n\tauthor = {Brunner, Andrea and Thalhammer-Thurner, Gudrun Carolina and Willenbacher, Wolfgang and Haun, Margot and Zelger, Bettina Gudrun and Willenbacher, Ella},\n\tmonth = nov,\n\tyear = {2023},\n\tkeywords = {DDM, Lymphoma, Lymphoma solution, Lymphoplasmacytic lymphoma, Mutations, Next-generation sequencing, Small B-cell lymphomas with plasmacytic differentiation, Waldenstroem’s macroglobulinemia},\n\tpages = {553--563},\n}\n\n

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\n \n\n \n \n \n \n \n \n One-step NGS molecular analysis of the CFTR gene on newborn dried blood spots gives a higher diagnostic sensitivity in affected and carrier subjects: A pilot study.\n \n \n \n \n\n\n \n Nunziato, M.; Starnone, F.; Giordano, S.; D'Antonio, M.; Scognamiglio, D.; Esposito, M. V.; Correra, A.; Di Maggio, F.; D'Argenio, V.; Luca Scaglione, G.; Castaldo, G.; and Salvatore, F.\n\n\n \n\n\n\n Clinica Chimica Acta, 552: 117625. November 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"One-step$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{nunziato_one-step_2023,\n\ttitle = {One-step {NGS} molecular analysis of the {CFTR} gene on newborn dried blood spots gives a higher diagnostic sensitivity in affected and carrier subjects: {A} pilot study},\n\tvolume = {552},\n\tissn = {0009-8981},\n\tshorttitle = {One-step {NGS} molecular analysis of the {CFTR} gene on newborn dried blood spots gives a higher diagnostic sensitivity in affected and carrier subjects},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0009898123004278},\n\tdoi = {10.1016/j.cca.2023.117625},\n\tabstract = {Background\nCystic fibrosis is the most common hereditary recessive disease with an incidence of about 1:2500/3000. It has long been known that the disease is caused by deleterious mutations in the CFTR gene. Conventionally, the disease is diagnosed in several phases. The analysis of all the possible disease-causing molecular alterations is time consuming and may not lead to a definitive diagnosis in several cases. Consequently, we propose, in this paper, a rapid sequencing method that, in a single procedural asset, reveals the presence of small mutations and also the copy number variants (CNVs) from the DNA extracted from the Guthrie Spot.\nMaterials and Methods\nWe first sequenced 30 blood spots, then we validated the method on 100 spots that underwent both traditional analyses and this complete NGS sequencing, and lastly, we tested the strategy on patients who normally do not reach the molecular sequencing step because of low level of Immune-Reactive Trypsinogen.\nResults\nUsing this procedure, we identified 97 variants in the CFTR gene of our samples and 6 CNVs. Notably, the significant data were obtained in the group of patients with borderline or negative IRT who routinely would not undergo molecular testing. We also identified 6 carriers of “disease-causing” variants.\nConclusion\nThis method is very robust. Indeed, there was a 100\\% concordance with Sanger sequencing validation, and 6 mutation carriers were identified who normally escaped molecular testing with actual conventional procedure. There were also 3 duplications of almost the entire gene in heterozygosity, which were not seen with traditional methods. Being quick and easy to perform, we suggest that complete sequencing of the CFTR gene, as in this study be considered for all newborns.},\n\turldate = {2024-01-23},\n\tjournal = {Clinica Chimica Acta},\n\tauthor = {Nunziato, Marcella and Starnone, Flavio and Giordano, Sonia and D'Antonio, Marcella and Scognamiglio, Domenico and Esposito, Maria Valeria and Correra, Antonio and Di Maggio, Federica and D'Argenio, Valeria and Luca Scaglione, Giovanni and Castaldo, Giuseppe and Salvatore, Francesco},\n\tmonth = nov,\n\tyear = {2023},\n\tkeywords = {Analytical sensitivity increase, Cystic fibrosis, DDM, DDM v.4, Guthrie dried blood spot, Next generation sequencing, One-step newborn screening},\n\tpages = {117625},\n}\n\n

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\n \n\n \n \n \n \n \n \n Novel Pathogenic Variants in the Gene Encoding Stereocilin (STRC) Causing Non-Syndromic Moderate Hearing Loss in Spanish and Argentinean Subjects.\n \n \n \n \n\n\n \n Domínguez-Ruiz, M.; Ruiz-Palmero, L.; Buonfiglio, P. I.; García-Vaquero, I.; Gómez-Rosas, E.; Goñi, M.; Villamar, M.; Morín, M.; Moreno-Pelayo, M. A.; Elgoyhen, A. B.; del Castillo, F. J.; Dalamón, V.; and del Castillo, I.\n\n\n \n\n\n\n Biomedicines, 11(11): 2943. October 2023.\n Number: 11 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Novel$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{dominguez-ruiz_novel_2023,\n\ttitle = {Novel {Pathogenic} {Variants} in the {Gene} {Encoding} {Stereocilin} ({STRC}) {Causing} {Non}-{Syndromic} {Moderate} {Hearing} {Loss} in {Spanish} and {Argentinean} {Subjects}},\n\tvolume = {11},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2227-9059},\n\turl = {https://www.mdpi.com/2227-9059/11/11/2943},\n\tdoi = {10.3390/biomedicines11112943},\n\tabstract = {Non-syndromic hearing impairment (NSHI) is a very heterogeneous genetic condition, involving over 130 genes. Mutations in GJB2, encoding connexin-26, are a major cause of NSHI (the DFNB1 type), but few other genes have significant epidemiological contributions. Mutations in the STRC gene result in the DFNB16 type of autosomal recessive NSHI, a common cause of moderate hearing loss. STRC is located in a tandem duplicated region that includes the STRCP1 pseudogene, and so it is prone to rearrangements causing structural variations. Firstly, we screened a cohort of 122 Spanish familial cases of non-DFNB1 NSHI with at least two affected siblings and unaffected parents, and with different degrees of hearing loss (mild to profound). Secondly, we screened a cohort of 64 Spanish sporadic non-DFNB1 cases, and a cohort of 35 Argentinean non-DFNB1 cases, all of them with moderate hearing loss. Amplification of marker D15S784, massively parallel DNA sequencing, multiplex ligation-dependent probe amplification and long-range gene-specific PCR followed by Sanger sequencing were used to search and confirm single-nucleotide variants (SNVs) and deletions involving STRC. Causative variants were found in 13 Spanish familial cases (10.7\\%), 5 Spanish simplex cases (7.8\\%) and 2 Argentinean cases (5.7\\%). In all, 34 deleted alleles and 6 SNVs, 5 of which are novel. All affected subjects had moderate hearing impairment. Our results further support this strong genotype–phenotype correlation and highlight the significant contribution of STRC mutations to moderate NSHI in the Spanish population.},\n\tlanguage = {en},\n\tnumber = {11},\n\turldate = {2024-01-23},\n\tjournal = {Biomedicines},\n\tauthor = {Domínguez-Ruiz, María and Ruiz-Palmero, Laura and Buonfiglio, Paula I. and García-Vaquero, Irene and Gómez-Rosas, Elena and Goñi, Marina and Villamar, Manuela and Morín, Matías and Moreno-Pelayo, Miguel A. and Elgoyhen, Ana B. and del Castillo, Francisco J. and Dalamón, Viviana and del Castillo, Ignacio},\n\tmonth = oct,\n\tyear = {2023},\n\tnote = {Number: 11\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {DDM, DFNB16, STRC, genetic epidemiology, non-syndromic hearing impairment, stereocilin},\n\tpages = {2943},\n}\n\n

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\n \n\n \n \n \n \n \n \n Theranostic biomarkers and PARP-inhibitors effectiveness in patients with non-BRCA associated homologous recombination deficient tumors: Still looking through a dirty glass window?.\n \n \n \n \n\n\n \n Incorvaia, L.; Perez, A.; Marchetti, C.; Brando, C.; Gristina, V.; Cancelliere, D.; Pivetti, A.; Contino, S.; Giovanni, E. D.; Barraco, N.; Bono, M.; Giurintano, A.; Russo, T. D. B.; Gottardo, A.; Cutaia, S.; Pedone, E.; Peri, M.; Corsini, L. R.; Fanale, D.; Galvano, A.; Scambia, G.; Badalamenti, G.; Russo, A.; and Bazan, V.\n\n\n \n\n\n\n Cancer Treatment Reviews, 121. October 2023.\n Publisher: Elsevier\n\n\n\n
\n\n\n\n \n \n $\"Theranostic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{incorvaia_theranostic_2023,\n\ttitle = {Theranostic biomarkers and {PARP}-inhibitors effectiveness in patients with non-{BRCA} associated homologous recombination deficient tumors: {Still} looking through a dirty glass window?},\n\tvolume = {121},\n\tissn = {0305-7372, 1532-1967},\n\tshorttitle = {Theranostic biomarkers and {PARP}-inhibitors effectiveness in patients with non-{BRCA} associated homologous recombination deficient tumors},\n\turl = {https://www.cancertreatmentreviews.com/article/S0305-7372(23)00143-3/fulltext},\n\tdoi = {10.1016/j.ctrv.2023.102650},\n\tlanguage = {English},\n\turldate = {2024-01-23},\n\tjournal = {Cancer Treatment Reviews},\n\tauthor = {Incorvaia, Lorena and Perez, Alessandro and Marchetti, Claudia and Brando, Chiara and Gristina, Valerio and Cancelliere, Daniela and Pivetti, Alessia and Contino, Silvia and Giovanni, Emilia Di and Barraco, Nadia and Bono, Marco and Giurintano, Ambra and Russo, Tancredi Didier Bazan and Gottardo, Andrea and Cutaia, Sofia and Pedone, Erika and Peri, Marta and Corsini, Lidia Rita and Fanale, Daniele and Galvano, Antonio and Scambia, Giovanni and Badalamenti, Giuseppe and Russo, Antonio and Bazan, Viviana},\n\tmonth = oct,\n\tyear = {2023},\n\tpmid = {37939446},\n\tnote = {Publisher: Elsevier},\n\tkeywords = {BRCA, Benchmark, Breast cancer, HRD, Homologous recombination deficiency, Homologous recombination repair, Ovarian cancer, PARP-inhibitors},\n}\n\n

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\n \n\n \n \n \n \n \n \n Bi-allelic truncating variants in CASP2 underlie a neurodevelopmental disorder with lissencephaly.\n \n \n \n \n\n\n \n Uctepe, E.; Vona, B.; Esen, F. N.; Sonmez, F. M.; Smol, T.; Tümer, S.; Mancılar, H.; Geylan Durgun, D. E.; Boute, O.; Moghbeli, M.; Ghayoor Karimiani, E.; Hashemi, N.; Bakhshoodeh, B.; Kim, H. G.; Maroofian, R.; and Yesilyurt, A.\n\n\n \n\n\n\n European Journal of Human Genetics, 32(1): 52–60. October 2023.\n Number: 1 Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"Bi-allelic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{uctepe_bi-allelic_2023,\n\ttitle = {Bi-allelic truncating variants in {CASP2} underlie a neurodevelopmental disorder with lissencephaly},\n\tvolume = {32},\n\tcopyright = {2023 The Author(s)},\n\tissn = {1476-5438},\n\turl = {https://www.nature.com/articles/s41431-023-01461-2},\n\tdoi = {10.1038/s41431-023-01461-2},\n\tabstract = {Lissencephaly (LIS) is a malformation of cortical development due to deficient neuronal migration and abnormal formation of cerebral convolutions or gyri. Thirty-one LIS-associated genes have been previously described. Recently, biallelic pathogenic variants in CRADD and PIDD1, have associated with LIS impacting the previously established role of the PIDDosome in activating caspase-2. In this report, we describe biallelic truncating variants in CASP2, another subunit of PIDDosome complex. Seven patients from five independent families presenting with a neurodevelopmental phenotype were identified through GeneMatcher-facilitated international collaborations. Exome sequencing analysis was carried out and revealed two distinct novel homozygous (NM\\_032982.4:c.1156delT (p.Tyr386ThrfsTer25), and c.1174 C {\\textgreater} T (p.Gln392Ter)) and compound heterozygous variants (c.[130 C {\\textgreater} T];[876 + 1 G {\\textgreater} T] p.[Arg44Ter];[?]) in CASP2 segregating within the families in a manner compatible with an autosomal recessive pattern. RNA studies of the c.876 + 1 G {\\textgreater} T variant indicated usage of two cryptic splice donor sites, each introducing a premature stop codon. All patients from whom brain MRIs were available had a typical fronto-temporal LIS and pachygyria, remarkably resembling the CRADD and PIDD1-related neuroimaging findings. Other findings included developmental delay, attention deficit hyperactivity disorder, hypotonia, seizure, poor social skills, and autistic traits. In summary, we present patients with CASP2-related ID, anterior-predominant LIS, and pachygyria similar to previously reported patients with CRADD and PIDD1-related disorders, expanding the genetic spectrum of LIS and lending support that each component of the PIDDosome complex is critical for normal development of the human cerebral cortex and brain function.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2024-01-23},\n\tjournal = {European Journal of Human Genetics},\n\tauthor = {Uctepe, Eyyup and Vona, Barbara and Esen, Fatma Nisa and Sonmez, F. Mujgan and Smol, Thomas and Tümer, Sait and Mancılar, Hanifenur and Geylan Durgun, Dilan Ece and Boute, Odile and Moghbeli, Meysam and Ghayoor Karimiani, Ehsan and Hashemi, Narges and Bakhshoodeh, Behnoosh and Kim, Hyung Goo and Maroofian, Reza and Yesilyurt, Ahmet},\n\tmonth = oct,\n\tyear = {2023},\n\tnote = {Number: 1\nPublisher: Nature Publishing Group},\n\tkeywords = {Alamut, Alamut Visual, Alamut Visual Plus v1.6.1, Disease genetics, Genetic testing, Genetics research, Neurodevelopmental disorders},\n\tpages = {52--60},\n}\n\n

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\n \n\n \n \n \n \n \n Implementation, Evolution, and Laboratory Performance of Methods-Based Proficiency Testing for Next-Generation Sequencing Detection of Germline Sequence Variants.\n \n \n \n\n\n \n Tsuchiya, K. D.; Funke, B.; Hegde, M.; Santani, A.; Souers, R. J.; Szelinger, S.; Halley, J.; Zhao, Q.; Mot, N.; Roy, A.; Smith, V. L.; Zhang, B. M.; Voelkerding, K.; and Moyer, A. M.\n\n\n \n\n\n\n Archives of Pathology & Laboratory Medicine. October 2023.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{tsuchiya_implementation_2023,\n\ttitle = {Implementation, {Evolution}, and {Laboratory} {Performance} of {Methods}-{Based} {Proficiency} {Testing} for {Next}-{Generation} {Sequencing} {Detection} of {Germline} {Sequence} {Variants}},\n\tissn = {1543-2165},\n\tdoi = {10.5858/arpa.2023-0090-CP},\n\tabstract = {CONTEXT.—: Next-generation sequencing (NGS)-based assays are used for diagnosis of diverse inherited disorders. Limited data are available pertaining to interlaboratory analytical performance of these assays.\nOBJECTIVE.—: To report on the College of American Pathologists (CAP) NGS Germline Program, which is methods based, and explore the evolution in laboratory testing practices.\nDESIGN.—: Results from the NGS Germline Program from 2016-2020 were analyzed for interlaboratory analytical performance. Self-reported laboratory testing practices were also evaluated.\nRESULTS.—: From 2016-2020, a total of 297 laboratories participated in at least 1 program mailing. Of the 289 laboratories that provided information on tests offered, 138 (47.8\\%) offered only panel testing throughout their enrollment, while 35 (12.1\\%) offered panels and exome testing, 30 (10.4\\%) offered only exomes, 9 (3.1\\%) offered only genomes, and 15 (5.2\\%) offered panels, exomes, and genomes. The remainder (62 laboratories, 21.4\\%) changed their test offerings during the 2016-2020 timeframe. Considering each genomic position/interval, the median detection percentage at variant positions across the 2016-2020 mailings ranged from 94.3\\% to 100\\%, while at reference positions (no variant detected), the median correct response percentage was 100\\% across all mailings. When considering performance of individual laboratories, 89.5\\% (136 of 152) to 98.0\\% (149 of 152) of laboratories successfully met the detection threshold (≥90\\% of the variants present), while 94.6\\% (87 of 92) to 100\\% (163 of 163) of laboratories met the 95\\% specificity threshold across mailings.\nCONCLUSIONS.—: Since the inception of this program, laboratories have consistently performed well. The median sensitivity and specificity of detection of sequence variants included in this program (eg, single nucleotide variants, insertions, and deletions) were 100.0\\%.},\n\tlanguage = {eng},\n\tjournal = {Archives of Pathology \\& Laboratory Medicine},\n\tauthor = {Tsuchiya, Karen D. and Funke, Birgit and Hegde, Madhuri and Santani, Avni and Souers, Rhona J. and Szelinger, Szabolcs and Halley, Jaimie and Zhao, Qin and Mot, Nicole and Roy, Angshumoy and Smith, Vanessa L. and Zhang, Bing M. and Voelkerding, Karl and Moyer, Ann M.},\n\tmonth = oct,\n\tyear = {2023},\n\tpmid = {37852169},\n\tkeywords = {Alamut Visual, Benchmark, NGS, NGS-next generation sequencing},\n}\n\n

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\n \n\n \n \n \n \n \n \n Detection of tumor DNA in bronchoscopic fluids in peripheral non small cell lung cancer: a proof-of-concept study.\n \n \n \n \n\n\n \n Arhant, G.; Lachkar, S.; Thiebaut, P.; Marguet, F.; Lamy, A.; Thiberville, L.; Salaün, M.; Guisier, F.; Sabourin, J.; and Piton, N.\n\n\n \n\n\n\n JTO Clinical and Research Reports,100596. October 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Detection$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{arhant_detection_2023,\n\ttitle = {Detection of tumor {DNA} in bronchoscopic fluids in peripheral non small cell lung cancer: a proof-of-concept study},\n\tissn = {2666-3643},\n\tshorttitle = {Detection of tumor {DNA} in bronchoscopic fluids in peripheral non small cell lung cancer},\n\turl = {https://www.sciencedirect.com/science/article/pii/S266636432300139X},\n\tdoi = {10.1016/j.jtocrr.2023.100596},\n\tabstract = {Background\nDNA Genotyping from plasma is a useful tool for molecular characterization of non-small cell lung cancer. However, the false negative rate justifies the development of methods with higher sensitivity, especially in difficult to reach peripheral lung tumours.\nResearch question\nWhat is the added value of molecular analysis from fluid collected during r-EBUS for peripheral lung cancer, compared to biopsy and circulating tumour DNA analyses?\nStudy design and methods\nWe aimed at comparing molecular analysis from the supernatant of guide sheath flush fluid collected during r-EBUS bronchoscopy to plasma sampling and tumour biopsies in patients with peripheral non-small cell lung cancer. DNA was genotyped using high-throughput sequencing or the COBAS® Mutation Test. Sixty-five patients with peripheral lung tumours were subjected to concomitant sampling of guide sheath flush supernatant, plasma tumour DNA and tumour biopsy/cytology using r-EBUS. Thirty-three patients (including 24 newly diagnosed non-small cell lung cancers) with an identifiable tumour mutation in the primary lesion were selected for the comparative analysis.\nResults\nGuide sheath flush-based genotyping yielded a mutation detection rate of 61.8\\% (17/24 mutated EGFR, 1/2 ERBB2, 1/1 KRAS, 1/1 MAP2K, 1/4 MET, and 0/1 STK11), compared to 33\\% in plasma-based genotyping (p = 0.0151). Furthermore, in the 8/34 r-EBUS without tumor cells on microscopic examination, we were able to detect the mutation in 4 paired guide sheath flush supernatant, compared to only 2 in paired plasma.\nInterpretation\nThe detection of tumor DNA in the supernatant of guide sheath flush fluid collected during r-EBUS bronchoscopy represents a sensitive and complementary method for genotyping non-small cell lung cancer.},\n\turldate = {2024-01-23},\n\tjournal = {JTO Clinical and Research Reports},\n\tauthor = {Arhant, Gwenaëlle and Lachkar, Samy and Thiebaut, Pierre-Alain and Marguet, Florent and Lamy, Aude and Thiberville, Luc and Salaün, Mathieu and Guisier, Florian and Sabourin, Jean-Christophe and Piton, Nicolas},\n\tmonth = oct,\n\tyear = {2023},\n\tkeywords = {Alamut, EGFR, Pulmonology, bronchoscopy, guide sheath flush, liquid biopsy, molecular biology, non-small cell lung carcinoma, peripheral lung nodule, radial-EndoBronchial UltraSound, targeted therapy, thoracic oncology, tumor DNA, tumor genotyping},\n\tpages = {100596},\n}\n\n

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\n \n\n \n \n \n \n \n Analysis of Turkish Breast Cancer Patients With ATM-Heterozygous Germline Mutation According to Clinicopathological Features.\n \n \n \n\n\n \n Ünsal, O.; Güvercin, B.; Özet, A.; and Ergün, M. A.\n\n\n \n\n\n\n Cureus, 15(10): e47324. October 2023.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{unsal_analysis_2023,\n\ttitle = {Analysis of {Turkish} {Breast} {Cancer} {Patients} {With} {ATM}-{Heterozygous} {Germline} {Mutation} {According} to {Clinicopathological} {Features}},\n\tvolume = {15},\n\tissn = {2168-8184},\n\tdoi = {10.7759/cureus.47324},\n\tabstract = {OBJECTIVE: The ATM gene is one of the most common breast cancer (BC) susceptibility genes after BRCA1/2 and has been shown to be a moderate BC susceptibility gene. The association between ATM germline mutation and clinical features of BC is now unknown. In this article, clinicopathological features of BC patients with ATM germline heterozygous mutation were investigated.\nMATERIALS AND METHODS: Patients admitted to the Medical Genetics department of a tertiary hospital between January 2020 and December 2022 were examined. Only invasive BC patients with pathogenic mutation, likely pathogenic mutation, or variants of uncertain significance (VUS) were included in the study.\nRESULTS: In all, 121 patients were included in the study. The median age at the first cancer diagnosis of the patients was 44 years. Of the total number of patients, 75.2\\% (91) had the histological subtype of infiltrating ductal carcinoma, and 43\\% (52) had Luminal B molecular subtype features. At a median follow-up of 16 months, 5.8\\% (7) of patients developed cancer in the contralateral breast. In addition, 7.4\\% (9) of the patients developed a second primary cancer during follow-up. When the patients were compared according to ATM variant classification, the localization, histologic types, and molecular subtypes of the BC were not different between all groups (respectively; p=0.68, p=0.65, p=0.32).\nCONCLUSIONS: To the best of our knowledge, this is the first publication that evaluates the clinical and pathological characteristics of BC patients with germline heterozygous ATM mutations in the Turkish population. When patients were compared according to variant classifications of ATM mutation, patients' histological and molecular subtypes were similar.},\n\tlanguage = {eng},\n\tnumber = {10},\n\tjournal = {Cureus},\n\tauthor = {Ünsal, Oktay and Güvercin, Büşra and Özet, Ahmet and Ergün, Mehmet Ali},\n\tmonth = oct,\n\tyear = {2023},\n\tpmid = {38021491},\n\tpmcid = {PMC10657162},\n\tkeywords = {DDM, HCS, HCS v.1, Hereditary Cancer Solution, atm, breast cancer, germline mutation, heterozygous, turkish population},\n\tpages = {e47324},\n}\n\n

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\n \n\n \n \n \n \n \n Genetic overlap between ALS and other neurodegenerative or neuromuscular disorders.\n \n \n \n\n\n \n Olsen, C. G.; Busk, Ø. L.; Holla, Ø. L.; Tveten, K.; Holmøy, T.; Tysnes, O.; and Høyer, H.\n\n\n \n\n\n\n Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration,1–11. October 2023.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{olsen_genetic_2023,\n\ttitle = {Genetic overlap between {ALS} and other neurodegenerative or neuromuscular disorders},\n\tissn = {2167-9223},\n\tdoi = {10.1080/21678421.2023.2270705},\n\tabstract = {Objective: In Norway, 89\\% of patients with Amyotrophic lateral sclerosis (ALS) lacks a genetic diagnose. ALS genes and genes that cause other neuromuscular or neurodegenerative disorders extensively overlap. This population-based study examined whether patients with ALS have a family history of neurological disorders and explored the occurrence of rare genetic variants associated with other neurodegenerative or neuromuscular disorders. Methods: During a two-year period, blood samples and clinical data from patients with ALS were collected from all 17 neurological departments in Norway. Our genetic analysis involved exome sequencing and bioinformatics filtering of 510 genes associated with neurodegenerative and neuromuscular disorders. The variants were interpreted using genotype-phenotype correlations and bioinformatics tools. Results: A total of 279 patients from a Norwegian population-based ALS cohort participated in this study. Thirty-one percent of the patients had first- or second-degree relatives with other neurodegenerative disorders, most commonly dementia and Parkinson's disease. The genetic analysis identified 20 possible pathogenic variants, in ATL3, AFG3L2, ATP7A, BICD2, HARS1, KIF1A, LRRK2, MSTO1, NEK1, NEFH, and SORL1, in 25 patients. NEK1 risk variants were present in 2.5\\% of this ALS cohort. Only four of the 25 patients reported relatives with other neurodegenerative or neuromuscular disorders. Conclusion: Gene variants known to cause other neurodegenerative or neuromuscular disorders, most frequently in NEK1, were identified in 9\\% of the patients with ALS. Most of these patients had no family history of other neurodegenerative or neuromuscular disorders. Our findings indicated that AFG3L2, ATP7A, BICD2, KIF1A, and MSTO1 should be further explored as potential ALS-causing genes.},\n\tlanguage = {eng},\n\tjournal = {Amyotrophic Lateral Sclerosis \\& Frontotemporal Degeneration},\n\tauthor = {Olsen, Cathrine Goberg and Busk, Øyvind Løvold and Holla, Øystein Lunde and Tveten, Kristian and Holmøy, Trygve and Tysnes, Ole-Bjørn and Høyer, Helle},\n\tmonth = oct,\n\tyear = {2023},\n\tpmid = {37849306},\n\tkeywords = {Alamut Visual, Amyotrophic lateral sclerosis, amyotrophic lateral sclerosis susceptibility, genetic analysis, pleiotropy},\n\tpages = {1--11},\n}\n\n

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\n \n\n \n \n \n \n \n NLRP12-associated autoinflammatory disease: much more than the FCAS phenotype.\n \n \n \n\n\n \n Demir, F.; and Sözeri, B.\n\n\n \n\n\n\n Clinical and Experimental Rheumatology, 41(10): 2115–2121. October 2023.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{demir_nlrp12-associated_2023,\n\ttitle = {{NLRP12}-associated autoinflammatory disease: much more than the {FCAS} phenotype},\n\tvolume = {41},\n\tissn = {0392-856X},\n\tshorttitle = {{NLRP12}-associated autoinflammatory disease},\n\tdoi = {10.55563/clinexprheumatol/kzggp3},\n\tabstract = {OBJECTIVES: NLRP12-associated autoinflammatory disease (NLRP12-AID) is a rarely seen periodic fever syndrome also known as familial cold autoinflammatory syndrome-2 (FCAS2), caused by autosomal dominant inherited mutations in the NLRP12 gene. We aimed to present our clinical experience constituting one of the largest paediatric NLRP12-AID cohort.\nMETHODS: The patients with preliminary diagnosis of systemic autoinflammatory disease (SAID) other than familial Mediterranean fever (FMF) and PFAPA syndrome were evaluated with the next-generation-sequence (NGS) genetic-panel analysis between January-2016 and January-2022. Among children carrying NLRP12-variant, patients with recurrent episodes of autoinflammatory disease manifestations were diagnosed with NLRP12-AID. Demographic, clinical and laboratory data, treatments and outcomes of patients were presented.\nRESULTS: Seventeen patients were diagnosed with NLRP12-AID. The mean age at diagnosis was 114.7±69.5 months. The most frequently seen clinical manifestations were respectively; fever (100\\%), arthritis/arthralgia (58.8\\%), rash (52.9\\%), abdominal pain (52.9\\%), diarrhoea (41.2\\%), myalgia/fatigue (53.2\\%) and, conjunctivitis (11.7\\%). Clinical manifestations were triggered by cold exposure in three patients (17.6\\%). Seven patients had pathogenic, one had likely pathogenic, seven had VUS, and two had novel heterozygous variants. The most common defined variant in the NLRP12 gene was R352C. Complete response was achieved in 5 patients and partial response was in 6 with colchicine treatment. Attacks were prevented with anti-IL-1 treatments in 6 patients unresponsive to colchicine.\nCONCLUSIONS: In conclusion, the disease can cause effects on various tissues, especially the musculoskeletal and gastrointestinal systems, apart from FCAS symptoms. We think that a patient who can be defined as syndrome of undifferentiated recurrent fever should also be evaluated genetically in terms of NLRP12 previously.},\n\tlanguage = {eng},\n\tnumber = {10},\n\tjournal = {Clinical and Experimental Rheumatology},\n\tauthor = {Demir, Ferhat and Sözeri, Betül},\n\tmonth = oct,\n\tyear = {2023},\n\tpmid = {37877365},\n\tkeywords = {Child, Colchicine, Cryopyrin-Associated Periodic Syndromes, Custom, Custom Panel, DDM, Familial Mediterranean Fever, Hereditary Autoinflammatory Diseases, Humans, Intracellular Signaling Peptides and Proteins, Phenotype, Syndrome},\n\tpages = {2115--2121},\n}\n\n

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\n \n\n \n \n \n \n \n \n Role of gene sequencing in classifying struma ovarii: BRAF p.G469A mutation and TERT promoter alterations favour malignant struma ovarii.\n \n \n \n \n\n\n \n Neyrand, S.; Trecourt, A.; Lopez, J.; Just, P. A.; Descotes, F.; Borson-Chazot, F.; Ray-Coquard, I.; Decaussin-Petrucci, M.; and Devouassoux-Shisheboran, M.\n\n\n \n\n\n\n Histopathology, 84(2): 291–300. September 2023.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/his.15052\n\n\n\n
\n\n\n\n \n \n $\"Role$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{neyrand_role_2023,\n\ttitle = {Role of gene sequencing in classifying struma ovarii: {BRAF} p.{G469A} mutation and {TERT} promoter alterations favour malignant struma ovarii},\n\tvolume = {84},\n\tcopyright = {© 2023 The Authors. Histopathology published by John Wiley \\& Sons Ltd.},\n\tissn = {1365-2559},\n\tshorttitle = {Role of gene sequencing in classifying struma ovarii},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1111/his.15052},\n\tdoi = {10.1111/his.15052},\n\tabstract = {Aims Struma ovarii (SO) are rare, accounting for 0.3–1\\% of ovarian tumours, and include benign and malignant lesions. In most cases, histology is not predictive of clinical outcome and prognosis. The prognosis of histologically malignant thyroid-type carcinomas can indeed be excellent, while SO, composed of normal thyroid tissue, can recur and are designated highly differentiated follicular carcinoma of the ovary. Clearer diagnostic criteria are therefore required. Methods and results We retrospectively studied 31 SO using DNA and RNA sequencing with pan-cancer gene panels, including eight biologically malignant SO (BMSO) defined based on ovarian serosal or extra-ovarian dissemination at presentation or during follow-up, 10 stage IA histologically malignant SO (HMSO) with thyroid-type carcinoma morphology and 13 biologically and histologically benign SO (BSO), with none of the above-mentioned characteristics. Molecular alterations were observed in 87.5\\% of BMSO, 70\\% of HMSO and 7.7\\% of BSO (P {\\textless} 0.001). All patients with a peritoneal dissemination at presentation or during follow-up had at least one gene alteration. BRAF mutations (44.5\\%) were only observed in malignant forms (HMSO and BMSO) and TERT promoter alterations (25\\%) only in cases of BMSO. The BRAF p.G469A mutation, which is extremely rare in thyroid carcinomas, was the molecular alteration most frequently associated with malignant SO (28.5\\%). Conclusion Our results highlight the clinical utility of molecular sequencing in SO, based on this limited number of cases. However, as malignant SO evolve slowly, more extensive molecular studies in SO with more than 10 years’ follow-up are required to draw any conclusions on the prognostic value of the associated gene alterations.},\n\tlanguage = {en},\n\tnumber = {2},\n\turldate = {2024-01-22},\n\tjournal = {Histopathology},\n\tauthor = {Neyrand, Sophie and Trecourt, Alexis and Lopez, Jonathan and Just, Pierre Alexandre and Descotes, Françoise and Borson-Chazot, Françoise and Ray-Coquard, Isabelle and Decaussin-Petrucci, Myriam and Devouassoux-Shisheboran, Mojgan},\n\tmonth = sep,\n\tyear = {2023},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/his.15052},\n\tkeywords = {BRAF, DDM, DDM v.4, HDFCO, STS, TERT alteration, gene mutation, malignant struma ovarii, struma ovarii},\n\tpages = {291--300},\n}\n\n

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\n \n\n \n \n \n \n \n \n Expanding the genotype–phenotype correlations in Alport syndrome: novel mutations, digenic inheritance, and genetic modifiers.\n \n \n \n \n\n\n \n Sahin, I.; Kandemir, N.; and Saat, H.\n\n\n \n\n\n\n Egyptian Journal of Medical Human Genetics, 24(1): 59. October 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Expanding$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{sahin_expanding_2023,\n\ttitle = {Expanding the genotype–phenotype correlations in {Alport} syndrome: novel mutations, digenic inheritance, and genetic modifiers},\n\tvolume = {24},\n\tissn = {2090-2441},\n\tshorttitle = {Expanding the genotype–phenotype correlations in {Alport} syndrome},\n\turl = {https://doi.org/10.1186/s43042-023-00441-x},\n\tdoi = {10.1186/s43042-023-00441-x},\n\tabstract = {Alport syndrome (AS) is the second most prevalent genetic cause of kidney failure, behind autosomal-dominant polycystic kidney disease, affecting at least one in 5000 individuals worldwide. AS is caused by COL4A3, COL4A4, and COL4A5 mutations. It is characterized as three distinct disorders of type IV collagen 3/4/5 based on a genetic evaluation: X-linked, autosomal, and digenic. About two-thirds of AS cases are X-linked (XLAS), 15\\% are autosomal recessive (ARAS), and 20\\% are autosomal dominant (ADAS). The spectrum of phenotypes associated with AS ranges from increasing renal disease with extrarenal abnormalities to isolated hematuria. Coinherited genetic mutations contribute significantly to clinical severity and variability.},\n\tnumber = {1},\n\turldate = {2024-01-22},\n\tjournal = {Egyptian Journal of Medical Human Genetics},\n\tauthor = {Sahin, Ibrahim and Kandemir, Nefise and Saat, Hanife},\n\tmonth = oct,\n\tyear = {2023},\n\tkeywords = {Alport syndrome, CES, COL4A3, COL4A4, COL4A5, DDM, Digenic, Genetic modifier},\n\tpages = {59},\n}\n\n

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\n \n\n \n \n \n \n \n \n Polyposis found on index colonoscopy in a 56-year-old female - BMPR1A variant in juvenile polyposis syndrome: A case report.\n \n \n \n \n\n\n \n Wu, M. Y.; Toon, C.; Field, M.; and Wong, M.\n\n\n \n\n\n\n World Journal of Gastrointestinal Endoscopy, 15(10): 623–628. October 2023.\n Publisher: Baishideng Publishing Group Inc.\n\n\n\n
\n\n\n\n \n \n $\"Polyposis$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{wu_polyposis_2023,\n\ttitle = {Polyposis found on index colonoscopy in a 56-year-old female - {BMPR1A} variant in juvenile polyposis syndrome: {A} case report},\n\tvolume = {15},\n\tshorttitle = {Polyposis found on index colonoscopy in a 56-year-old female - {BMPR1A} variant in juvenile polyposis syndrome},\n\turl = {https://www.wjgnet.com/1948-5190/full/v15/i10/623.htm},\n\tdoi = {10.4253/wjge.v15.i10.623},\n\tabstract = {Polyposis found on index colonoscopy in a 56-year-old female - BMPR1A variant in juvenile polyposis syndrome: A case report},\n\tlanguage = {en},\n\tnumber = {10},\n\turldate = {2024-01-22},\n\tjournal = {World Journal of Gastrointestinal Endoscopy},\n\tauthor = {Wu, Michael Yulong and Toon, Christopher and Field, Michael and Wong, May},\n\tmonth = oct,\n\tyear = {2023},\n\tnote = {Publisher: Baishideng Publishing Group Inc.},\n\tkeywords = {DDM},\n\tpages = {623--628},\n}\n\n

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\n \n\n \n \n \n \n \n \n Different Phenotypes of a New Mutation: Two Siblings with ADA-2 Deficiency Presenting with Anemia and Neutropenia (Case Reports and Literature Review). \\textbar Asthma Allergy Immunology / Astim Allerji Immunoloji \\textbar EBSCOhost.\n \n \n \n \n\n\n \n Ozdemir, O.; Orhan, M. F.; Buyukavci, M.; Yilmaz, E. A.; and Gorukmez, O.\n\n\n \n\n\n\n August 2023.\n ISSN: 1308-9234 Issue: 2 Pages: 143 Volume: 21\n\n\n\n
\n\n\n\n \n \n $\"Different$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@misc{ozdemir_different_2023,\n\ttitle = {Different {Phenotypes} of a {New} {Mutation}: {Two} {Siblings} with {ADA}-2 {Deficiency} {Presenting} with {Anemia} and {Neutropenia} ({Case} {Reports} and {Literature} {Review}). {\\textbar} {Asthma} {Allergy} {Immunology} / {Astim} {Allerji} {Immunoloji} {\\textbar} {EBSCOhost}},\n\tshorttitle = {Different {Phenotypes} of a {New} {Mutation}},\n\turl = {https://openurl.ebsco.com/contentitem/doi:10.21911%2Faai.102?sid=ebsco:plink:crawler&id=ebsco:doi:10.21911%2Faai.102},\n\tlanguage = {en},\n\turldate = {2024-01-22},\n\tauthor = {Ozdemir, Oner and Orhan, Mehmet Fatih and Buyukavci, Mustafa and Yilmaz, Emine Aylin and Gorukmez, Orhan},\n\tmonth = aug,\n\tyear = {2023},\n\tdoi = {10.21911/aai.102},\n\tnote = {ISSN: 1308-9234\nIssue: 2\nPages: 143\nVolume: 21},\n\tkeywords = {Custom, Custom Panel, Hereditary periodic fever syndromes panel},\n}\n\n

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\n \n\n \n \n \n \n \n \n Combined Presence in Heterozygosis of Two Variant Usher Syndrome Genes in Two Siblings Affected by Isolated Profound Age-Related Hearing Loss.\n \n \n \n \n\n\n \n Borgese, N.; Guillén-Samander, A.; Colombo, S. F.; Mancassola, G.; Di Berardino, F.; Zanetti, D.; and Carrera, P.\n\n\n \n\n\n\n Biomedicines, 11(10): 2657. September 2023.\n Number: 10 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Combined$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{borgese_combined_2023,\n\ttitle = {Combined {Presence} in {Heterozygosis} of {Two} {Variant} {Usher} {Syndrome} {Genes} in {Two} {Siblings} {Affected} by {Isolated} {Profound} {Age}-{Related} {Hearing} {Loss}},\n\tvolume = {11},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2227-9059},\n\turl = {https://www.mdpi.com/2227-9059/11/10/2657},\n\tdoi = {10.3390/biomedicines11102657},\n\tabstract = {Sensorineural age-related hearing loss affects a large proportion of the elderly population, and has both environmental and genetic causes. Notwithstanding increasing interest in this debilitating condition, the genetic risk factors remain largely unknown. Here, we report the case of two sisters affected by isolated profound sensorineural hearing loss after the age of seventy. Genomic DNA sequencing revealed that the siblings shared two monoallelic variants in two genes linked to Usher Syndrome (USH genes), a recessive disorder of the ear and the retina: a rare pathogenic truncating variant in USH1G and a previously unreported missense variant in ADGRV1. Structure predictions suggest a negative effect on protein stability of the latter variant, allowing its classification as likely pathogenic according to American College of Medical Genetics criteria. Thus, the presence in heterozygosis of two recessive alleles, which each cause syndromic deafness, may underlie digenic inheritance of the age-related non-syndromic hearing loss of the siblings, a hypothesis that is strengthened by the knowledge that the two genes are integrated in the same functional network, which underlies stereocilium development and organization. These results enlarge the spectrum and complexity of the phenotypic consequences of USH gene mutations beyond the simple Mendelian inheritance of classical Usher syndrome.},\n\tlanguage = {en},\n\tnumber = {10},\n\turldate = {2024-01-22},\n\tjournal = {Biomedicines},\n\tauthor = {Borgese, Nica and Guillén-Samander, Andrés and Colombo, Sara Francesca and Mancassola, Giulia and Di Berardino, Federica and Zanetti, Diego and Carrera, Paola},\n\tmonth = sep,\n\tyear = {2023},\n\tnote = {Number: 10\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {ADGRV1, Alamut Visual Plus, SANS, Usher gene network, haploinsufficiency, nonsyndromic deafness},\n\tpages = {2657},\n}\n\n

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\n \n\n \n \n \n \n \n \n ATP7B Gene Variant Profile İdentified by NGS in Wilson’s Disease.\n \n \n \n \n\n\n \n Gorukmez, O.; Özgür, T.; Gorukmez, O.; and Topak, A.\n\n\n \n\n\n\n Fetal and Pediatric Pathology, 0(0): 1–10. September 2023.\n Publisher: Taylor & Francis _eprint: https://doi.org/10.1080/15513815.2023.2260005\n\n\n\n
\n\n\n\n \n \n $\"ATP7B$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{gorukmez_atp7b_2023,\n\ttitle = {{ATP7B} {Gene} {Variant} {Profile} İdentified by {NGS} in {Wilson}’s {Disease}},\n\tvolume = {0},\n\tissn = {1551-3815},\n\turl = {https://doi.org/10.1080/15513815.2023.2260005},\n\tdoi = {10.1080/15513815.2023.2260005},\n\tabstract = {Background: Wilson’s disease (WD) is a copper metabolism disorder caused by ATP7B gene mutations and shows an autosomal recessive pattern of inheritance. We aimed to contribute to the mutation profile of ATP7B and show demographic and phenotypic differences in this study. Materials and methods: The clinical and demographic characteristics of patients who underwent ATP7B gene sequence analysis using next-generation sequencing were evaluated to improve genotype-phenotype correlation in WD. Results: An uncertain significance (D563N) and seven likely pathogenic (Y532D, Y715Y, T977K, K1028*, E1086K, A1227Pfs*103, and E1242K) variants were identified as associated with WD. Uniparental disomy was detected in one case. Conclusion: Our work expanded the ATP7B variant spectrum and pointed to clinical heterogeneity in ATP7B variants among patients with WD. All symptomatic patients had hepatic involvement and were clinically and/or genetically diagnosed with WD in the pediatric period. T977K, A1003V, H1069Q, E1086K, and N1270S variants were associated with hepatic failure.},\n\tnumber = {0},\n\turldate = {2023-10-19},\n\tjournal = {Fetal and Pediatric Pathology},\n\tauthor = {Gorukmez, Orhan and Özgür, Taner and Gorukmez, Ozlem and Topak, Ali},\n\tmonth = sep,\n\tyear = {2023},\n\tpmid = {37737146},\n\tnote = {Publisher: Taylor \\& Francis\n\\_eprint: https://doi.org/10.1080/15513815.2023.2260005},\n\tkeywords = {ATP7B, DDM, NGS, Wilson’s disease},\n\tpages = {1--10},\n}\n\n

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\n \n\n \n \n \n \n \n \n Expression profiling of extramedullary acute myeloid leukemia suggests involvement of epithelial–mesenchymal transition pathways.\n \n \n \n \n\n\n \n Ottone, T.; Silvestrini, G.; Piazza, R.; Travaglini, S.; Gurnari, C.; Marchesi, F.; Nardozza, A. M.; Fabiani, E.; Attardi, E.; Guarnera, L.; Divona, M.; Ricci, P.; Irno Consalvo, M. A.; Ienzi, S.; Arcese, R.; Biagi, A.; Fiori, L.; Novello, M.; Mauriello, A.; Venditti, A.; Anemona, L.; and Voso, M. T.\n\n\n \n\n\n\n Leukemia,1–12. October 2023.\n Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"Expression$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{ottone_expression_2023,\n\ttitle = {Expression profiling of extramedullary acute myeloid leukemia suggests involvement of epithelial–mesenchymal transition pathways},\n\tcopyright = {2023 The Author(s), under exclusive licence to Springer Nature Limited},\n\tissn = {1476-5551},\n\turl = {https://www.nature.com/articles/s41375-023-02054-0},\n\tdoi = {10.1038/s41375-023-02054-0},\n\tabstract = {Extramedullary (EM) colonization is a rare complication of acute myeloid leukemia (AML), occurring in about 10\\% of patients, but the processes underlying tissue invasion are not entirely characterized. Through the application of RNAseq technology, we examined the transcriptome profile of 13 AMLs, 9 of whom presented an EM localization. Our analysis revealed significant deregulation within the extracellular matrix (ECM)-receptor interaction and focal-adhesion pathways, specifically in the EM sites. The transcription factor TWIST1, which is known to impact on cancer invasion by dysregulating epithelial–mesenchymal-transition (EMT) processes, was significantly upregulated in EM-AML. To test the functional impact of TWIST1 overexpression, we treated OCI-AML3s with TWIST1-siRNA or metformin, a drug known to inhibit tumor progression in cancer models. After 48 h, we showed downregulation of TWIST1, and of the EMT-related genes FN1 and SNAI2. This was associated with significant impairment of migration and invasion processes by Boyden chamber assays. Our study shed light on the molecular mechanisms associated with EM tissue invasion in AML, and on the ability of metformin to interfere with key players of this process. TWIST1 may configure as candidate marker of EM-AML progression, and inhibition of EMT-pathways may represent an innovative therapeutic intervention to prevent or treat this complication.},\n\tlanguage = {en},\n\turldate = {2023-10-19},\n\tjournal = {Leukemia},\n\tauthor = {Ottone, T. and Silvestrini, G. and Piazza, R. and Travaglini, S. and Gurnari, C. and Marchesi, F. and Nardozza, A. M. and Fabiani, E. and Attardi, E. and Guarnera, L. and Divona, M. and Ricci, P. and Irno Consalvo, M. A. and Ienzi, S. and Arcese, R. and Biagi, A. and Fiori, L. and Novello, M. and Mauriello, A. and Venditti, A. and Anemona, L. and Voso, M. T.},\n\tmonth = oct,\n\tyear = {2023},\n\tnote = {Publisher: Nature Publishing Group},\n\tkeywords = {Acute myeloid leukaemia, DDM, Haematological diseases, MYS, Myeloid},\n\tpages = {1--12},\n}\n\n

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\n \n\n \n \n \n \n \n \n Ovarian high-grade serous carcinoma with transitional-like (SET) morphology: a homologous recombination-deficient tumor.\n \n \n \n \n\n\n \n D'Angelo, E.; Espinosa, I.; Felicioni, L.; Buttitta, F.; and Prat, J.\n\n\n \n\n\n\n Human Pathology, 141: 15–21. November 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Ovarian$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{dangelo_ovarian_2023,\n\ttitle = {Ovarian high-grade serous carcinoma with transitional-like ({SET}) morphology: a homologous recombination-deficient tumor},\n\tvolume = {141},\n\tissn = {0046-8177},\n\tshorttitle = {Ovarian high-grade serous carcinoma with transitional-like ({SET}) morphology},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0046817723001855},\n\tdoi = {10.1016/j.humpath.2023.08.010},\n\tabstract = {Thirteen years ago, we pointed out that ovarian transitional cell carcinomas (TCCs) and conventional high-grade serous carcinomas (HGSCs) had similar genetic alterations and clinical behavior. Consequently, ovarian TCC is now classified as a morphologic variant of HGSC. Defective homologous recombination, resulting from genetic or epigenetic inactivation of DNA damage repair genes, such as BRCA1/2, occurs in approximately 50\\% of the HGSCs. Although BRCA mutations have been associated with HGSCs with solid, pseudoendometrioid or transitional (SET) features, little is known about the role of non-BRCA homologous recombinationrepair (HRR) genes and the HRR status in these tumors. Using two commercially available assays (Myriad Genetics MyChoice CDx Plus test and SOPHiA Dx Homologous Recombination Deficiency Solution), we study mutations of BRCA1/2 and non-BRCA HRR genes (ATM, BARD1, BRIP1, CDK12, CHEK1/2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L), and the HRR status in 19 HGSCs with SET features and 20 HGSCs with classic morphology. We also studied, as control cases, 5 endometrioid carcinomas, 1 clear cell carcinoma, 2 low-grade serous carcinomas, and 1 malignant Brenner tumor. Seven HGSCs with SET features (7/19; 37\\%) showed BRCA mutations (4 BRCA1, 2 BRCA2, and 1 BRCA1/2). Mutations in non-BRCA HRR genes were found in ATM (1/15; 7\\%), BARD1 (1/15; 7\\%), and BRIP1 (1/19; 5\\%). Most HGSCs with SET features (17/19; 90\\%) were considered to be homologous recombination-deficient tumors. Three HGSCs with classic morphology (3/20; 15\\%) showed BRCA2 mutations. Mutations in non-BRCA HRR genes were found in CDK12 (2/14; 14\\%), FANCL (1/14; 7\\%), RAD51B (1/14; 7\\%), and RAD54L (1/14; 7\\%). Eleven HGSCs with classical morphology (11/20; 55\\%) were considered to be homologous recombination deficient. In contrast, all ovarian carcinoma control cases (5 endometrioid carcinomas, 1 clear cell carcinoma, 2 low-grade serous carcinomas, and 1 malignant Brenner tumor) were homologous recombination proficient and did not have BRCA mutations. Our results show that the majority of HGSCs with SET features are homologous recombination-deficient tumors independently of the BRCA status and highlight the importance of the HRR tumor testing, especially in BRCA wild-type tumors. Recognition of transitional cell variant of HGSCs may help to identify patients most likely to benefit from PARP inhibitors.},\n\turldate = {2023-10-19},\n\tjournal = {Human Pathology},\n\tauthor = {D'Angelo, Emanuela and Espinosa, Iñigo and Felicioni, Lara and Buttitta, Fiamma and Prat, Jaime},\n\tmonth = nov,\n\tyear = {2023},\n\tkeywords = {HRD, High-grade serous carcinoma, Homologous recombination deficiency, SET features, Transitional-like morphology},\n\tpages = {15--21},\n}\n\n

\n\n\n

\n Thirteen years ago, we pointed out that ovarian transitional cell carcinomas (TCCs) and conventional high-grade serous carcinomas (HGSCs) had similar genetic alterations and clinical behavior. Consequently, ovarian TCC is now classified as a morphologic variant of HGSC. Defective homologous recombination, resulting from genetic or epigenetic inactivation of DNA damage repair genes, such as BRCA1/2, occurs in approximately 50% of the HGSCs. Although BRCA mutations have been associated with HGSCs with solid, pseudoendometrioid or transitional (SET) features, little is known about the role of non-BRCA homologous recombinationrepair (HRR) genes and the HRR status in these tumors. Using two commercially available assays (Myriad Genetics MyChoice CDx Plus test and SOPHiA Dx Homologous Recombination Deficiency Solution), we study mutations of BRCA1/2 and non-BRCA HRR genes (ATM, BARD1, BRIP1, CDK12, CHEK1/2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L), and the HRR status in 19 HGSCs with SET features and 20 HGSCs with classic morphology. We also studied, as control cases, 5 endometrioid carcinomas, 1 clear cell carcinoma, 2 low-grade serous carcinomas, and 1 malignant Brenner tumor. Seven HGSCs with SET features (7/19; 37%) showed BRCA mutations (4 BRCA1, 2 BRCA2, and 1 BRCA1/2). Mutations in non-BRCA HRR genes were found in ATM (1/15; 7%), BARD1 (1/15; 7%), and BRIP1 (1/19; 5%). Most HGSCs with SET features (17/19; 90%) were considered to be homologous recombination-deficient tumors. Three HGSCs with classic morphology (3/20; 15%) showed BRCA2 mutations. Mutations in non-BRCA HRR genes were found in CDK12 (2/14; 14%), FANCL (1/14; 7%), RAD51B (1/14; 7%), and RAD54L (1/14; 7%). Eleven HGSCs with classical morphology (11/20; 55%) were considered to be homologous recombination deficient. In contrast, all ovarian carcinoma control cases (5 endometrioid carcinomas, 1 clear cell carcinoma, 2 low-grade serous carcinomas, and 1 malignant Brenner tumor) were homologous recombination proficient and did not have BRCA mutations. Our results show that the majority of HGSCs with SET features are homologous recombination-deficient tumors independently of the BRCA status and highlight the importance of the HRR tumor testing, especially in BRCA wild-type tumors. Recognition of transitional cell variant of HGSCs may help to identify patients most likely to benefit from PARP inhibitors.\n

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\n \n\n \n \n \n \n \n \n All-CLL: A Capture-based Next-generation Sequencing Panel for the Molecular Characterization of Chronic Lymphocytic Leukemia.\n \n \n \n \n\n\n \n López-Oreja, I.; López-Guerra, M.; Correa, J.; Mozas, P.; Muntañola, A.; Muñoz, L.; Salgado, A.; Ruiz-Gaspà, S.; Costa, D.; Beà, S.; Jares, P.; Campo, E.; Colomer, D.; and Nadeu, F.\n\n\n \n\n\n\n HemaSphere, 7(10). September 2023.\n Publisher: Wolters Kluwer Health\n\n\n\n
\n\n\n\n \n \n $\"All-CLL:$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{lopez-oreja_all-cll_2023,\n\ttitle = {All-{CLL}: {A} {Capture}-based {Next}-generation {Sequencing} {Panel} for the {Molecular} {Characterization} of {Chronic} {Lymphocytic} {Leukemia}},\n\tvolume = {7},\n\tshorttitle = {All-{CLL}},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10516383/},\n\tdoi = {10.1097/HS9.0000000000000962},\n\tlanguage = {en},\n\tnumber = {10},\n\turldate = {2023-10-18},\n\tjournal = {HemaSphere},\n\tauthor = {López-Oreja, Irene and López-Guerra, Mónica and Correa, Juan and Mozas, Pablo and Muntañola, Ana and Muñoz, Luz and Salgado, Ana-Camino and Ruiz-Gaspà, Sílvia and Costa, Dolors and Beà, Sílvia and Jares, Pedro and Campo, Elías and Colomer, Dolors and Nadeu, Ferran},\n\tmonth = sep,\n\tyear = {2023},\n\tpmid = {37746159},\n\tnote = {Publisher: Wolters Kluwer Health},\n\tkeywords = {CLL, Chronic lymphocytic leukaemia, Custom Cancer Panel, Custom Panel},\n}\n\n

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\n \n\n \n \n \n \n \n \n Ophthalmologic Phenotype–Genotype Correlations in Patients With Oculocutaneous Albinism Followed in a Reference Center.\n \n \n \n \n\n\n \n Seguy, P.; Korobelnik, J.; Delyfer, M.; Michaud, V.; Arveiler, B.; Lasseaux, E.; Gattoussi, S.; Rougier, M.; Trin, K.; Morice-Picard, F.; Ghomashchi, N.; and Coste, V.\n\n\n \n\n\n\n Investigative Ophthalmology & Visual Science, 64(12): 26. September 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Ophthalmologic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{seguy_ophthalmologic_2023,\n\ttitle = {Ophthalmologic {Phenotype}–{Genotype} {Correlations} in {Patients} {With} {Oculocutaneous} {Albinism} {Followed} in a {Reference} {Center}},\n\tvolume = {64},\n\tissn = {1552-5783},\n\turl = {https://doi.org/10.1167/iovs.64.12.26},\n\tdoi = {10.1167/iovs.64.12.26},\n\tabstract = {Albinism is a group of genetic disorders that includes several conditions related to a defect in melanin production. There is a broad phenotypic and genotypic variability between the different forms. The aim of this study was to assess the ophthalmologic characteristics according to patients’ genotypes in a cohort followed in the Reference Center for oculocutaneous albinism (OCA) of Bordeaux University Hospital, France.    A retrospective observational study was conducted in a cohort of patients with OCA seen in consultation in the ophthalmology department between 2017 and 2021 in whom a genetic analysis was performed.    In total, 127 patients with OCA were included in this study and matched with the results of the genetic analysis. In the population aged over 6 years, there was no statistical difference in binocular visual acuity between the OCA1, OCA2, and OCA4 forms (P = 0.27). There was difference in ametropia between the three forms (P = 0.003). A two-by-two comparison using the Bonferroni correction showed a significant difference in ametropia between the OCA2 and OCA4 forms (P = 0.007) and between the OCA1 and OCA2 forms (P = 0.0075). Regardless of the form, most patients (75.4\\%) had grade 4 foveal hypoplasia. There was no association between the grade of foveal hypoplasia and the gene involved (P = 0.87).    We described a genotype–phenotype correlation for the three most represented forms of albinism in our cohort. This study allowed assessing the degree of visual deficiency in young children with OCA.},\n\tnumber = {12},\n\turldate = {2023-10-18},\n\tjournal = {Investigative Ophthalmology \\& Visual Science},\n\tauthor = {Seguy, Paul-Henri and Korobelnik, Jean-François and Delyfer, Marie-Noëlle and Michaud, Vincent and Arveiler, Benoit and Lasseaux, Eulalie and Gattoussi, Sarra and Rougier, Marie-Bénédicte and Trin, Kilian and Morice-Picard, Fanny and Ghomashchi, Nathalie and Coste, Valentine},\n\tmonth = sep,\n\tyear = {2023},\n\tkeywords = {Alamut Visual, OCT, albinism, choroid, foveal hypoplasia, genetic diseases},\n\tpages = {26},\n}\n\n

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\n \n\n \n \n \n \n \n \n Single-cell multi-omics identifies chronic inflammation as a driver of TP53-mutant leukemic evolution.\n \n \n \n \n\n\n \n Rodriguez-Meira, A.; Norfo, R.; Wen, S.; Chédeville, A. L.; Rahman, H.; O’Sullivan, J.; Wang, G.; Louka, E.; Kretzschmar, W. W.; Paterson, A.; Brierley, C.; Martin, J.; Demeule, C.; Bashton, M.; Sousos, N.; Moralli, D.; Subha Meem, L.; Carrelha, J.; Wu, B.; Hamblin, A.; Guermouche, H.; Pasquier, F.; Marzac, C.; Girodon, F.; Vainchenker, W.; Drummond, M.; Harrison, C.; Chapman, J. R.; Plo, I.; Jacobsen, S. E. W.; Psaila, B.; Thongjuea, S.; Antony-Debré, I.; and Mead, A. J.\n\n\n \n\n\n\n Nature Genetics, 55(9): 1531–1541. September 2023.\n Number: 9 Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"Single-cell$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{rodriguez-meira_single-cell_2023,\n\ttitle = {Single-cell multi-omics identifies chronic inflammation as a driver of {TP53}-mutant leukemic evolution},\n\tvolume = {55},\n\tcopyright = {2023 The Author(s)},\n\tissn = {1546-1718},\n\turl = {https://www.nature.com/articles/s41588-023-01480-1},\n\tdoi = {10.1038/s41588-023-01480-1},\n\tabstract = {Understanding the genetic and nongenetic determinants of tumor protein 53 (TP53)-mutation-driven clonal evolution and subsequent transformation is a crucial step toward the design of rational therapeutic strategies. Here we carry out allelic resolution single-cell multi-omic analysis of hematopoietic stem/progenitor cells (HSPCs) from patients with a myeloproliferative neoplasm who transform to TP53-mutant secondary acute myeloid leukemia (sAML). All patients showed dominant TP53 ‘multihit’ HSPC clones at transformation, with a leukemia stem cell transcriptional signature strongly predictive of adverse outcomes in independent cohorts, across both TP53-mutant and wild-type (WT) AML. Through analysis of serial samples, antecedent TP53-heterozygous clones and in vivo perturbations, we demonstrate a hitherto unrecognized effect of chronic inflammation, which suppressed TP53 WT HSPCs while enhancing the fitness advantage of TP53-mutant cells and promoted genetic evolution. Our findings will facilitate the development of risk-stratification, early detection and treatment strategies for TP53-mutant leukemia, and are of broad relevance to other cancer types.},\n\tlanguage = {en},\n\tnumber = {9},\n\turldate = {2023-10-18},\n\tjournal = {Nature Genetics},\n\tauthor = {Rodriguez-Meira, Alba and Norfo, Ruggiero and Wen, Sean and Chédeville, Agathe L. and Rahman, Haseeb and O’Sullivan, Jennifer and Wang, Guanlin and Louka, Eleni and Kretzschmar, Warren W. and Paterson, Aimee and Brierley, Charlotte and Martin, Jean-Edouard and Demeule, Caroline and Bashton, Matthew and Sousos, Nikolaos and Moralli, Daniela and Subha Meem, Lamia and Carrelha, Joana and Wu, Bishan and Hamblin, Angela and Guermouche, Helene and Pasquier, Florence and Marzac, Christophe and Girodon, François and Vainchenker, William and Drummond, Mark and Harrison, Claire and Chapman, J. Ross and Plo, Isabelle and Jacobsen, Sten Eirik W. and Psaila, Bethan and Thongjuea, Supat and Antony-Debré, Iléana and Mead, Adam J.},\n\tmonth = sep,\n\tyear = {2023},\n\tnote = {Number: 9\nPublisher: Nature Publishing Group},\n\tkeywords = {Cancer stem cells, DDM, Leukaemia, Transcriptomics},\n\tpages = {1531--1541},\n}\n\n

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\n \n\n \n \n \n \n \n \n Heterozygosity of ALG9 in Association with Autosomal Dominant Polycystic Liver Disease.\n \n \n \n \n\n\n \n Boerrigter, M. M.; Duijzer, R.; te Morsche, R. H. M.; and Drenth, J. P. H.\n\n\n \n\n\n\n Genes, 14(9): 1755. September 2023.\n Number: 9 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Heterozygosity$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{boerrigter_heterozygosity_2023,\n\ttitle = {Heterozygosity of {ALG9} in {Association} with {Autosomal} {Dominant} {Polycystic} {Liver} {Disease}},\n\tvolume = {14},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2073-4425},\n\turl = {https://www.mdpi.com/2073-4425/14/9/1755},\n\tdoi = {10.3390/genes14091755},\n\tabstract = {α-1,2-mannosyltransferase (ALG9) germline variants are linked to autosomal dominant polycystic kidney disease (ADPKD). Many individuals affected with ADPKD possess polycystic livers as a common extrarenal manifestation. We performed whole exome sequencing in a female with autosomal dominant polycystic liver disease (ADPLD) without kidney cysts and established the presence of a heterozygous missense variant (c.677G{\\textgreater}C p.(Gly226Ala)) in ALG9. In silico pathogenicity prediction and 3D protein modeling determined this variant as pathogenic. Loss of heterozygosity is regularly seen in liver cyst walls. Immunohistochemistry indicated the absence of ALG9 in liver tissue from this patient. ALG9 expression was absent in cyst wall lining from ALG9- and PRKCSH-caused ADPLD patients but present in the liver cyst lining derived from an ADPKD patient with a PKD2 variant. Thus, heterozygous pathogenic variants in ALG9 are also associated with ADPLD. Somatic loss of heterozygosity of the ALG9 enzyme was seen in the ALG9 patient but also in ADPLD patients with a different genetic background. This expanded the phenotypic spectrum of ADPLD to ALG9.},\n\tlanguage = {en},\n\tnumber = {9},\n\turldate = {2023-10-18},\n\tjournal = {Genes},\n\tauthor = {Boerrigter, Melissa M. and Duijzer, Renée and te Morsche, René H. M. and Drenth, Joost P. H.},\n\tmonth = sep,\n\tyear = {2023},\n\tnote = {Number: 9\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {ADPLD, ALG9, Alamut Visual Plus, Alamut Visual Plus v.1.4, PCLD, cyst wall, polycystic liver disease (PLD), whole exome sequencing},\n\tpages = {1755},\n}\n\n

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\n \n\n \n \n \n \n \n Evaluation of common NLRP3 Q703K variant in pediatric patients with autoinflammatory disease: CAPS and PFAPA.\n \n \n \n\n\n \n Kendir-Demirkol, Y.; Jenny, L. A.; Demir, F.; and Sözeri, B.\n\n\n \n\n\n\n The Turkish Journal of Pediatrics, 65(4): 650–660. August 2023.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{kendir-demirkol_evaluation_2023,\n\ttitle = {Evaluation of common {NLRP3} {Q703K} variant in pediatric patients with autoinflammatory disease: {CAPS} and {PFAPA}},\n\tvolume = {65},\n\tissn = {2791-6421},\n\tshorttitle = {Evaluation of common {NLRP3} {Q703K} variant in pediatric patients with autoinflammatory disease},\n\tdoi = {10.24953/turkjped.2023.166},\n\tabstract = {BACKGROUND: Gain-of-function mutations of the NLR family pyrin domain containing 3 (NLRP3) gene have been implicated in autoinflammatory diseases. The NLRP3 Q703K variant is a common variant associated with Cryopyrin-associated periodic syndromes (CAPS) and periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome. However, the genotype-phenotype correlation between NLRP3 Q703K variant, CAPS and PFAPA is unclear. In this study, we aimed to investigate the frequency of the NLRP3 Q703K variant in patients with and without autoinflammatory disease and characterize the phenotype in only Q703K variant positive patients.\nMETHODS: A retrospective analysis of 639 patients with autoinflammatory symptoms was conducted. Patients underwent next-generation sequencing (NGS) panel analysis of 16 genes, including NLRP3. For the 68 patients carrying the only Q703K variant, their clinical and demographic information was evaluated. Genetic data from 1461 patients without autoinflammatory symptoms were used as the control group.\nRESULTS: Of our 639 autoinflammatory symptomatic patients, the Q703K mutation was detected in 68 (5.3\\% allele frequency). Heterozygous mutations were detected in 141 patients without autoinflammatory symptoms (4.8\\% allele frequency, p=0.4887). Of the patients with variant in Q703K, 10 patients were diagnosed with CAPS , 7 patients were diagnosed with PFAPA and the remaining 39 were diagnosed with undefined systemic autoinflammatory disease (uSAID) Conclusions. The Q703K variant, which is seen with similar frequency in the control and autoinflammatory groups, is also of higher prevalence in patients with mild CAPS symptoms and PFAPA syndrome. This variant, together with other undetected genetic variants or epigenetic modifications, may be responsible for the corresponding phenotype. As such, it is essential for clinicians to evaluate their patients using both genetic and clinical evaluations.},\n\tlanguage = {eng},\n\tnumber = {4},\n\tjournal = {The Turkish Journal of Pediatrics},\n\tauthor = {Kendir-Demirkol, Yasemin and Jenny, Laura A. and Demir, Ferhat and Sözeri, Betül},\n\tmonth = aug,\n\tyear = {2023},\n\tpmid = {37661680},\n\tkeywords = {CES, Clinical Exome Solution, Cryopyrin-Associated Periodic Syndromes, Custom Panel, DDM, Gene Frequency, Heterozygote, Humans, Lymphadenopathy, NLR Family, Pyrin Domain-Containing 3 Protein, Pharyngitis, Retrospective Studies, aphthous stomatitis, clinical exome sequencing, cryopyrin-associated periodic syndromes; periodic fever, pharyngitis and cervical adenitis; NLRP3 gene; Q703K variant},\n\tpages = {650--660},\n}\n\n

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\n \n\n \n \n \n \n \n \n Heterozygous TP63 pathogenic variants in isolated primary ovarian insufficiency.\n \n \n \n \n\n\n \n Vanderschelden, R. K.; Rodriguez-Escriba, M.; Chan, S. H.; Berman, A. J.; Rajkovic, A.; and Yatsenko, S. A.\n\n\n \n\n\n\n Journal of Assisted Reproduction and Genetics, 40(9): 2211–2218. September 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Heterozygous$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{vanderschelden_heterozygous_2023,\n\ttitle = {Heterozygous {TP63} pathogenic variants in isolated primary ovarian insufficiency},\n\tvolume = {40},\n\tissn = {1573-7330},\n\turl = {https://doi.org/10.1007/s10815-023-02886-w},\n\tdoi = {10.1007/s10815-023-02886-w},\n\tabstract = {Our study aimed to identify the genetic causes of non-syndromic primary ovarian insufficiency (POI) in female patients.},\n\tlanguage = {en},\n\tnumber = {9},\n\turldate = {2023-10-18},\n\tjournal = {Journal of Assisted Reproduction and Genetics},\n\tauthor = {Vanderschelden, Rachel K. and Rodriguez-Escriba, Marta and Chan, Serena H. and Berman, Andrea J. and Rajkovic, Aleksandar and Yatsenko, Svetlana A.},\n\tmonth = sep,\n\tyear = {2023},\n\tkeywords = {DDM, DNA repair, Isolated POI, Pleiotropy, Primary ovarian insufficiency, TP63, WES, Whole exome sequencing},\n\tpages = {2211--2218},\n}\n\n

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\n \n\n \n \n \n \n \n \n Recombinant von Willebrand factor and tranexamic acid for heavy menstrual bleeding in patients with mild and moderate von Willebrand disease in the USA (VWDMin): a phase 3, open-label, randomised, crossover trial.\n \n \n \n \n\n\n \n Ragni, M. V.; Rothenberger, S. D.; Feldman, R.; Nance, D.; Leavitt, A. D.; Malec, L.; Kulkarni, R.; Sidonio, R.; Kraut, E.; Lasky, J.; Pruthi, R.; Angelini, D.; Philipp, C.; Hwang, N.; Wheeler, A. P.; Seaman, C.; Machin, N.; Xavier, F.; Meyer, M.; Bellissimo, D.; Humphreys, G.; Smith, K. J.; Merricks, E. P.; Nichols, T. C.; Ivanco, D.; Vehec, D.; Koerbel, G.; and Althouse, A. D.\n\n\n \n\n\n\n The Lancet Haematology, 10(8): e612–e623. August 2023.\n Publisher: Elsevier\n\n\n\n
\n\n\n\n \n \n $\"Recombinant$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{ragni_recombinant_2023,\n\ttitle = {Recombinant von {Willebrand} factor and tranexamic acid for heavy menstrual bleeding in patients with mild and moderate von {Willebrand} disease in the {USA} ({VWDMin}): a phase 3, open-label, randomised, crossover trial},\n\tvolume = {10},\n\tissn = {2352-3026},\n\tshorttitle = {Recombinant von {Willebrand} factor and tranexamic acid for heavy menstrual bleeding in patients with mild and moderate von {Willebrand} disease in the {USA} ({VWDMin})},\n\turl = {https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(23)00119-9/fulltext},\n\tdoi = {10.1016/S2352-3026(23)00119-9},\n\tlanguage = {English},\n\tnumber = {8},\n\turldate = {2023-10-18},\n\tjournal = {The Lancet Haematology},\n\tauthor = {Ragni, Margaret V. and Rothenberger, Scott D. and Feldman, Robert and Nance, Danielle and Leavitt, Andrew D. and Malec, Lynn and Kulkarni, Roshni and Sidonio, Robert and Kraut, Eric and Lasky, Joseph and Pruthi, Rajiv and Angelini, Dana and Philipp, Claire and Hwang, Nina and Wheeler, Allison P. and Seaman, Craig and Machin, Nicoletta and Xavier, Frederico and Meyer, Michael and Bellissimo, Daniel and Humphreys, Gregory and Smith, Kenneth J. and Merricks, Elizabeth P. and Nichols, Timothy C. and Ivanco, Dana and Vehec, Deborah and Koerbel, Glory and Althouse, Andrew D.},\n\tmonth = aug,\n\tyear = {2023},\n\tpmid = {37385272},\n\tnote = {Publisher: Elsevier},\n\tkeywords = {CES, Clinical Exome Solution, DDM, clinical exome sequencing, von Willebrand disease},\n\tpages = {e612--e623},\n}\n\n

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\n \n\n \n \n \n \n \n \n Identification of a novel pathogenic deep intronic variant in PTEN resulting in pseudoexon inclusion in a patient with juvenile polyps.\n \n \n \n \n\n\n \n Jelsig, A. M.; Rønlund, K.; Gede, L. B.; Frederiksen, J. H.; Karstensen, J. G.; Birkedal, U.; and van Overeem Hansen, T.\n\n\n \n\n\n\n Journal of Human Genetics, 68(10): 721–724. June 2023.\n Number: 10 Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"Identification$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{jelsig_identification_2023,\n\ttitle = {Identification of a novel pathogenic deep intronic variant in {PTEN} resulting in pseudoexon inclusion in a patient with juvenile polyps},\n\tvolume = {68},\n\tcopyright = {2023 The Japan Society of Human Genetics},\n\tissn = {1435-232X},\n\turl = {https://www.nature.com/articles/s10038-023-01174-w},\n\tdoi = {10.1038/s10038-023-01174-w},\n\tabstract = {Colorectal, hamartomatous juvenile polyps occur as part of different hereditary syndromes, including Juvenile polyposis syndrome and PTEN-hamartoma tumour syndrome. However, based on clinical manifestations alone, it is difficult to differentiate between the syndromes, and genetic analysis with an NGS-panel is often used to aid diagnostics. We report a 59-year-old male with colorectal juvenile polyps, who had been referred to genetic testing but had normal genetic analysis. He did not fulfil the clinical criteria of PTEN- hamartoma tumour syndrome, but the clinical criteria of Juvenile polyposis syndrome. With Whole Genome Sequencing we detected a novel intronic variant of unknown significance in PTEN (NC\\_000010.11:g.89687361 A {\\textgreater} G(chr10, hg19), NM\\_000314.8:c.209 + 2047 A {\\textgreater} G). RNA analysis classified the variant as likely pathogenic as it results in a pseudoexon inclusion introducing a frameshift and a premature stop codon. The patient was then diagnosed with PTEN-hamartoma Tumour syndrome. To our knowledge this is the first report of a variant resulting in pseudoexon inclusion in PTEN.},\n\tlanguage = {en},\n\tnumber = {10},\n\turldate = {2023-10-18},\n\tjournal = {Journal of Human Genetics},\n\tauthor = {Jelsig, Anne Marie and Rønlund, Karina and Gede, Lene Bjerring and Frederiksen, Jane Hübertz and Karstensen, John Gásdal and Birkedal, Ulf and van Overeem Hansen, Thomas},\n\tmonth = jun,\n\tyear = {2023},\n\tnote = {Number: 10\nPublisher: Nature Publishing Group},\n\tkeywords = {Alamut, Cancer genetics, Genotype},\n\tpages = {721--724},\n}\n\n

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\n \n\n \n \n \n \n \n \n Mild TSC phenotype and non-penetrance associated with a frameshift variant in TSC2 prompts caution in evaluating pathogenicity of frameshift variants.\n \n \n \n \n\n\n \n Farach, L. S.; Northrup, H.; Nellist, M.; van Unen, L.; Hillman, P.; Klonowska, K.; Ekong, R.; Crino, P. B.; and Au, K. S.\n\n\n \n\n\n\n Gene, 877: 147566. August 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Mild$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{farach_mild_2023,\n\ttitle = {Mild {TSC} phenotype and non-penetrance associated with a frameshift variant in {TSC2} prompts caution in evaluating pathogenicity of frameshift variants},\n\tvolume = {877},\n\tissn = {0378-1119},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0378111923004079},\n\tdoi = {10.1016/j.gene.2023.147566},\n\tabstract = {Introduction\nTechnological advances in genetic testing, particularly the adoption of noninvasive prenatal screening (NIPS) for single gene disorders such as tuberous sclerosis complex (TSC, OMIM\\# 613254), mean that putative/possible pathogenetic DNA variants can be identified prior to the appearance of a disease phenotype. Without a phenotype, accurate prediction of variant pathogenicity is crucial. Here, we report a TSC2 frameshift variant, NM\\_000548.5(TSC2):c.4255\\_4256delCA, predicted to result in nonsense-mediated mRNA decay (NMD) and cessation of TSC2 protein production and thus pathogenic according to ACMG criteria, identified by NIPS and subsequently detected in family members with few or no symptoms of TSC. Due to the lack of TSC-associated features in the family, we hypothesized that the deletion created a non-canonical 5′ donor site resulting in cryptic splicing and a transcript encoding active TSC2 protein. Verifying the predicted effect of the variant was key to designating pathogenicity in this case and should be considered for other frameshift variants in other genetic disorders.\nMethods\nPhenotypic information on the family members was collected via review of the medical records and patient reports. RNA studies were performed using proband mRNA isolated from blood lymphocytes for RT-PCR and Sanger sequencing. Functional studies were performed by transient expression of the TSC2 variant proteins in cultured cells, followed by immunoblotting.\nResults\nNo family members harboring the variant met any major clinical diagnostic criteria for TSC, though a few minor features non-specific to TSC were present. RNA studies supported the hypothesis that the variant caused cryptic splicing, resulting in an mRNA transcript with an in-frame deletion of 93 base pairs r.[4255\\_4256del, 4251\\_4343del], p.[(Gln1419Valfs*104), (Gln1419\\_Ser1449del)]. Expression studies demonstrated that the canonical function of the resulting truncated TSC2 p.Gln1419\\_Ser1449del protein product was maintained and similar to wildtype.\nConclusion\nAlthough most frameshift variants are likely to result in NMD, the NM\\_000548.5(TSC2):c.4255\\_4256delCA variant creates a cryptic 5′ splice donor site, resulting in an in-frame deletion that retains TSC2 function, explaining why carriers of the variant do not have typical features of TSC. The information is important for this family and others with the same variant. Equally important is the lesson that predictions can be inaccurate, and that caution should be used when designating frameshift variants as pathogenic, especially when phenotypic information to corroborate testing results is unavailable. Our work demonstrates that functional RNA- and protein-based confirmation of the effects of DNA variants improves molecular genetic diagnostics.},\n\turldate = {2023-10-18},\n\tjournal = {Gene},\n\tauthor = {Farach, Laura S. and Northrup, Hope and Nellist, Mark and van Unen, Leontine and Hillman, Paul and Klonowska, Katarzyna and Ekong, Rosemary and Crino, Peter B. and Au, Kit Sing},\n\tmonth = aug,\n\tyear = {2023},\n\tkeywords = {Alamut Visual Plus, Alamut Visual Plus v.1.7, Genetic counseling, Genotype phenotype association, Non-invasive prenatal screening, Tuberous sclerosis complex},\n\tpages = {147566},\n}\n\n

\n\n\n

\n Introduction Technological advances in genetic testing, particularly the adoption of noninvasive prenatal screening (NIPS) for single gene disorders such as tuberous sclerosis complex (TSC, OMIM# 613254), mean that putative/possible pathogenetic DNA variants can be identified prior to the appearance of a disease phenotype. Without a phenotype, accurate prediction of variant pathogenicity is crucial. Here, we report a TSC2 frameshift variant, NM_000548.5(TSC2):c.4255_4256delCA, predicted to result in nonsense-mediated mRNA decay (NMD) and cessation of TSC2 protein production and thus pathogenic according to ACMG criteria, identified by NIPS and subsequently detected in family members with few or no symptoms of TSC. Due to the lack of TSC-associated features in the family, we hypothesized that the deletion created a non-canonical 5′ donor site resulting in cryptic splicing and a transcript encoding active TSC2 protein. Verifying the predicted effect of the variant was key to designating pathogenicity in this case and should be considered for other frameshift variants in other genetic disorders. Methods Phenotypic information on the family members was collected via review of the medical records and patient reports. RNA studies were performed using proband mRNA isolated from blood lymphocytes for RT-PCR and Sanger sequencing. Functional studies were performed by transient expression of the TSC2 variant proteins in cultured cells, followed by immunoblotting. Results No family members harboring the variant met any major clinical diagnostic criteria for TSC, though a few minor features non-specific to TSC were present. RNA studies supported the hypothesis that the variant caused cryptic splicing, resulting in an mRNA transcript with an in-frame deletion of 93 base pairs r.[4255_4256del, 4251_4343del], p.[(Gln1419Valfs*104), (Gln1419_Ser1449del)]. Expression studies demonstrated that the canonical function of the resulting truncated TSC2 p.Gln1419_Ser1449del protein product was maintained and similar to wildtype. Conclusion Although most frameshift variants are likely to result in NMD, the NM_000548.5(TSC2):c.4255_4256delCA variant creates a cryptic 5′ splice donor site, resulting in an in-frame deletion that retains TSC2 function, explaining why carriers of the variant do not have typical features of TSC. The information is important for this family and others with the same variant. Equally important is the lesson that predictions can be inaccurate, and that caution should be used when designating frameshift variants as pathogenic, especially when phenotypic information to corroborate testing results is unavailable. Our work demonstrates that functional RNA- and protein-based confirmation of the effects of DNA variants improves molecular genetic diagnostics.\n

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\n \n\n \n \n \n \n \n \n BCR-ABL1 co-occurring with CBFA2T3-GLIS2 and RAM immunophenotype in a non-Down syndrome infant with acute megakaryoblastic leukemia.\n \n \n \n \n\n\n \n de Matos, R. R. C.; Ferreira, G. M.; Bonecker, S.; Rouxinol, M.; da Costa, E. S.; Mello, F. V.; Abdelhay, E.; Ribeiro, R. C.; Zalcberg, I.; and Silva, M. L. M.\n\n\n \n\n\n\n Leukemia & Lymphoma, 0(0): 1–5. August 2023.\n Publisher: Taylor & Francis _eprint: https://doi.org/10.1080/10428194.2023.2243532\n\n\n\n
\n\n\n\n \n \n $\"BCR-ABL1$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{de_matos_bcr-abl1_2023,\n\ttitle = {{BCR}-{ABL1} co-occurring with {CBFA2T3}-{GLIS2} and {RAM} immunophenotype in a non-{Down} syndrome infant with acute megakaryoblastic leukemia},\n\tvolume = {0},\n\tissn = {1042-8194},\n\turl = {https://doi.org/10.1080/10428194.2023.2243532},\n\tdoi = {10.1080/10428194.2023.2243532},\n\tnumber = {0},\n\turldate = {2023-10-16},\n\tjournal = {Leukemia \\& Lymphoma},\n\tauthor = {de Matos, Roberto R. Capela and Ferreira, Gerson Moura and Bonecker, Simone and Rouxinol, Mainá and da Costa, Elaine Sobral and Mello, Fabiana V. and Abdelhay, Eliana and Ribeiro, Raul C. and Zalcberg, Ilana and Silva, Maria Luiza Macedo},\n\tmonth = aug,\n\tyear = {2023},\n\tpmid = {37548333},\n\tnote = {Publisher: Taylor \\& Francis\n\\_eprint: https://doi.org/10.1080/10428194.2023.2243532},\n\tkeywords = {MYS plus, MYS+},\n\tpages = {1--5},\n}\n\n

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\n \n\n \n \n \n \n \n \n Association of ABCA4 Gene Variants in Patients with Autosomal Recessive Cone-Rod Dystrophy and Retinitis Pigmentosa Cohorts from South India.\n \n \n \n \n\n\n \n Kadarkarai Raj Rajendran; Chermakani, P.; Anjanamurthy, R.; Rencilin, C. F.; and Sundaresan, P.\n\n\n \n\n\n\n Cytology and Genetics, 57(3): 258–267. June 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Association$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{kadarkarai_raj_rajendran_association_2023,\n\ttitle = {Association of {ABCA4} {Gene} {Variants} in {Patients} with {Autosomal} {Recessive} {Cone}-{Rod} {Dystrophy} and {Retinitis} {Pigmentosa} {Cohorts} from {South} {India}},\n\tvolume = {57},\n\tissn = {1934-9440},\n\turl = {https://doi.org/10.3103/S0095452723030088},\n\tdoi = {10.3103/S0095452723030088},\n\tabstract = {Background: The purpose of this study is to determine the genetic association and compare the distribution of ABCA4 gene variants in patients with various inherited retinal dystrophies, including autosomal recessive cone-rod dystrophy (AR-CRD) autosomal recessive retinitis pigmentosa (AR-RP) in the South Indian cohorts. Methods: This study included nineteen probands, ophthalmic examination of all the probands were carefully evaluated by the Paediatric Ophthalmologist. Eleven of the nineteen probands had the clinical phenotype of AR-CRD, eight showed AR-RP-like clinical phenotype. Genomic DNA was extracted from their peripheral blood, the exon and intronic boundaries of the ABCA4 gene were screened using the Sanger sequencing to identify the genetic association of these two retinal dystrophies. Results: Sanger sequencing results revealed that only 18\\% (2/11) of AR-CRD probands had disease-causing ABCA4 mutations, while the remaining 9 AR-CRD, 8 AR-RP were negative for the pathogenic variant associated with ABCA4. Furthermore, this study identified 18 common SNPs of the ABCA4 (2 missense, 3 synonymous, 13 intronic variants) and found them associated with AR-CRD and AR-RP probands. Conclusion:This is the first study to show that two missense variants in the ABCA4 (c.302T {\\textgreater} C, c.1319A {\\textgreater} G) are associated with AR-CRD probands and two rare NNCS variants (c.3191-10G {\\textgreater} T, c.3814-5G {\\textgreater} A) associated with AR-RP patients from the South Indian population.},\n\tlanguage = {en},\n\tnumber = {3},\n\turldate = {2023-10-16},\n\tjournal = {Cytology and Genetics},\n\tauthor = {{Kadarkarai Raj Rajendran} and Chermakani, Prakash and Anjanamurthy, Rupa and Rencilin, Clayton Fernando and Sundaresan, Periasamy},\n\tmonth = jun,\n\tyear = {2023},\n\tkeywords = {ABCA4, AR-CRD, AR-RP, Alamut visual v.1.1, Biointeractive Software, France), South Indian cohort, intronic variants},\n\tpages = {258--267},\n}\n\n

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\n \n\n \n \n \n \n \n \n An Integral Approach to the Molecular Diagnosis of Tuberous Sclerosis Complex: The Role of Mosaicism and Splicing Variants.\n \n \n \n \n\n\n \n Blasco-Pérez, L.; Iranzo-Nuez, L.; López-Ortega, R.; Martínez-Cruz, D.; Camprodon-Gómez, M.; Tenés, A.; Antolín, M.; Tizzano, E. F.; and García-Arumí, E.\n\n\n \n\n\n\n The Journal of Molecular Diagnostics, 25(9): 692–701. September 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"An$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{blasco-perez_integral_2023,\n\ttitle = {An {Integral} {Approach} to the {Molecular} {Diagnosis} of {Tuberous} {Sclerosis} {Complex}: {The} {Role} of {Mosaicism} and {Splicing} {Variants}},\n\tvolume = {25},\n\tissn = {1525-1578},\n\tshorttitle = {An {Integral} {Approach} to the {Molecular} {Diagnosis} of {Tuberous} {Sclerosis} {Complex}},\n\turl = {https://www.sciencedirect.com/science/article/pii/S1525157823001344},\n\tdoi = {10.1016/j.jmoldx.2023.06.006},\n\tabstract = {Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by the presence of hamartomas in multiple organs. At the molecular level, the disease is caused by pathogenic variants in the TSC1 and TSC2 genes, and only 10\\% to 25\\% of clinically diagnosed patients remain negative after multiplex ligation-dependent probe amplification and exon sequencing of both genes. Here, to improve the molecular diagnosis of TSC, we developed an integral approach that includes multiplex ligation-dependent probe amplification and deep-coverage next-generation sequencing of the entire TSC1 and TSC2 genes, along with an adapted bioinformatic pipeline to detect variants at low allele frequencies ({\\textgreater}1\\%). Using this workflow, the molecular cause was identified in 29 of 42 patients with TSC, describing here, for the first time, 12 novel pathogenic variants in TSC genes. These variants included seven splicing variants, five of which were studied at the cDNA level, determining their effect on splicing. In addition, 8 of the 29 pathogenic variants were detected in mosaicism, including four patients with previous negative study results who presented extremely low mosaic variants (allele frequency, {\\textless}16\\%). We demonstrate that this integral approach allows the molecular diagnosis of patients with TSC and improves the conventional one by adapting the technology to the detection of low-frequency mosaics.},\n\tnumber = {9},\n\turldate = {2023-10-16},\n\tjournal = {The Journal of Molecular Diagnostics},\n\tauthor = {Blasco-Pérez, Laura and Iranzo-Nuez, Leticia and López-Ortega, Ricard and Martínez-Cruz, Desirée and Camprodon-Gómez, María and Tenés, Anna and Antolín, María and Tizzano, Eduardo F. and García-Arumí, Elena},\n\tmonth = sep,\n\tyear = {2023},\n\tkeywords = {Alamut Visual Plus v.1.5.1, DDM},\n\tpages = {692--701},\n}\n\n

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\n \n\n \n \n \n \n \n \n A shared origin from a common ancestor: A case report of two histologically different tumors.\n \n \n \n \n\n\n \n Varea-Martínez, M.; García-Valero, E.; López-Reig, R.; Romero, I.; Machado, I.; Gómez-Ferrer, Á.; Aliaga, J.; Claramunt-Alonso, R.; Fernández-Serra, A.; Marenco-Jiménez, J. L.; García-Casado, Z.; and López-Guerrero, J. A.\n\n\n \n\n\n\n Pathology - Research and Practice, 248: 154648. June 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{varea-martinez_shared_2023,\n\ttitle = {A shared origin from a common ancestor: {A} case report of two histologically different tumors},\n\tvolume = {248},\n\tissn = {0344-0338},\n\tshorttitle = {A shared origin from a common ancestor},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0344033823003485},\n\tdoi = {10.1016/j.prp.2023.154648},\n\tabstract = {The origin of tumors has been under discussion over the years. Different theories have been suggested to explain this phenomenon. Among them, the Cancer-Stem Cells model, is one of the most outstanding. In this study, we reported a case of a 72-year-old man who presented two histologically different tumors with a 7-years gap, a Penile Squamous Cell Carcinoma and a Pleomorphic Undifferentiated Sarcoma, that share some molecular features. Phonotypical differences were showed and confirmed at histological and IHC levels. Molecular analysis showed an HPV infection in the carcinoma. Additionally, sequencing results revealed common (CDKN2A and TERT) and exclusive (FBXW7 and TP53) genetic alterations in both tumors (Table 1). The possible germline origin of common mutations was discarded after negative germline testing. Here we describe, for the first time a clinical case of a possible origin of two histologically different tumors from a common ancestor based on molecular data. Even if different hypothesis appear as possible, the Cancer Stem Cell-based model appears as the most suitable.},\n\turldate = {2023-10-16},\n\tjournal = {Pathology - Research and Practice},\n\tauthor = {Varea-Martínez, Maria and García-Valero, Eva and López-Reig, Raquel and Romero, Ignacio and Machado, Isidro and Gómez-Ferrer, Álvaro and Aliaga, Jessica and Claramunt-Alonso, Reyes and Fernández-Serra, Antonio and Marenco-Jiménez, José L. and García-Casado, Zaida and López-Guerrero, José Antonio},\n\tmonth = jun,\n\tyear = {2023},\n\tkeywords = {Cancer stem Cell, Case Report, DDM, DDM v.5.10.31, HCS, Next-generation sequencing, Penile Squamous cell carcinoma, Penile sarcoma, STS},\n\tpages = {154648},\n}\n\n

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\n \n\n \n \n \n \n \n \n Uncovering the expression of circPVT1 in the extracellular vesicles of acute myeloid leukemia patients.\n \n \n \n \n\n\n \n Ghetti, M.; Vannini, I.; Bochicchio, M. T.; Azzali, I.; Ledda, L.; Marconi, G.; Melloni, M.; Fabbri, F.; Rondoni, M.; Chicchi, R.; Angeli, D.; Ghelli Luserna di Rorà, A.; Giannini, B.; Zacheo, I.; Biguzzi, R.; Lanza, F.; Martinelli, G.; and Simonetti, G.\n\n\n \n\n\n\n Biomedicine & Pharmacotherapy, 165: 115235. September 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Uncovering$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{ghetti_uncovering_2023,\n\ttitle = {Uncovering the expression of {circPVT1} in the extracellular vesicles of acute myeloid leukemia patients},\n\tvolume = {165},\n\tissn = {0753-3322},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0753332223010260},\n\tdoi = {10.1016/j.biopha.2023.115235},\n\tabstract = {Extracellular vesicles (EVs) act as molecular mediators in the tumor microenvironment, by shuttling information contained within malignant cells and functioning as regulators of the immune system. Circular (circ)RNAs are characterized by a closed loop-like structure that makes them more stable in the extracellular milieu and suitable to be packaged inside EVs. circPVT1 (hsa\\_circ\\_0001821) showed an oncogenic role in several cancer types and immunosuppressive properties in myeloid and lymphoid cell subsets. In this study, we characterized EVs from acute myeloid leukemia (AML) patients in terms of size, concentrations, surface markers and circPVT1 cargo. We showed that circPVT1 is overexpressed by primary blast cells from newly-diagnosed AML patients compared with hematopoietic stem-progenitor cells and is released as cell-free RNA in the plasma. We isolated EVs from the plasma of AML patients and healthy subjects by size exclusion chromatography and characterized them by nanoparticle tracking analysis. EVs from patients’ plasma are larger compared with those from healthy subjects and their surface profile is characterized by higher levels of the leukemic cell markers CD133, CD105, CD49e and other immune-related epitopes, with differences according to AML molecular profile. Moreover, digital PCR analysis revealed that circPVT1 is more abundant inside EVs from the plasma of AML patients compared with healthy subjects. Our findings provide new insights on the features and content of AML EVs and suggest a role of circPVT1 in the crosstalk between AML cells and the tumor microenvironment.},\n\turldate = {2023-08-25},\n\tjournal = {Biomedicine \\& Pharmacotherapy},\n\tauthor = {Ghetti, Martina and Vannini, Ivan and Bochicchio, Maria Teresa and Azzali, Irene and Ledda, Lorenzo and Marconi, Giovanni and Melloni, Mattia and Fabbri, Francesco and Rondoni, Michela and Chicchi, Roberta and Angeli, Davide and Ghelli Luserna di Rorà, Andrea and Giannini, Barbara and Zacheo, Irene and Biguzzi, Rino and Lanza, Francesco and Martinelli, Giovanni and Simonetti, Giorgia},\n\tmonth = sep,\n\tyear = {2023},\n\tkeywords = {Acute myeloid leukemia, CirRNA, CircPVT1, DDM, Extracellular vesicles, Immune system, MYS, Myeloid},\n\tpages = {115235},\n}\n\n

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\n \n\n \n \n \n \n \n \n Aggressive B-cell non-Hodgkin lymphomas: a report of the lymphoma workshop of the 20th meeting of the European Association for Haematopathology.\n \n \n \n \n\n\n \n Rodriguez-Pinilla, S. M.; Docjinov, S.; Dotlic, S.; Gibson, S. E.; Hartmann, S.; Klimkowska, M.; Sabattini, E.; Tousseyn, T. A.; de Jong, D.; and Hsi, E. D.\n\n\n \n\n\n\n Virchows Archiv. August 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Aggressive$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{rodriguez-pinilla_aggressive_2023,\n\ttitle = {Aggressive {B}-cell non-{Hodgkin} lymphomas: a report of the lymphoma workshop of the 20th meeting of the {European} {Association} for {Haematopathology}},\n\tissn = {1432-2307},\n\tshorttitle = {Aggressive {B}-cell non-{Hodgkin} lymphomas},\n\turl = {https://doi.org/10.1007/s00428-023-03579-6},\n\tdoi = {10.1007/s00428-023-03579-6},\n\tabstract = {Aggressive B-cell non-Hodgkin lymphomas are a heterogeneous group of diseases and our concepts are evolving as we learn more about their clinical, pathologic, molecular genetic features. Session IV of the 2020 EAHP Workshop covered aggressive, predominantly high-grade B-cell lymphomas, many that were difficult to classify. In this manuscript, we summarize the features of the submitted cases and highlight differential diagnostic difficulties. We specifically review issues related to high-grade B-cell lymphomas (HGBCLs) with MYC and BCL2 and/or BCL6 rearrangements including TdT expression in these cases, HGBCL, not otherwise specified, large B-cell lymphomas with IRF4 rearrangement, high-grade/large B-cell lymphomas with 11q aberration, Burkitt lymphoma, and pleomorphic mantle cell lymphoma. Since the workshop, the 5th edition of the WHO Classification for Haematolymphoid Tumours (WHO-HAEM5) and International Consensus Classification (ICC) 2022 were published. We endeavor to use the updated terminology.},\n\tlanguage = {en},\n\turldate = {2023-08-25},\n\tjournal = {Virchows Archiv},\n\tauthor = {Rodriguez-Pinilla, Socorro Maria and Docjinov, Stefan and Dotlic, Snjezana and Gibson, Sarah E. and Hartmann, Sylvia and Klimkowska, Monika and Sabattini, Elena and Tousseyn, Thomas A. and de Jong, Daphne and Hsi, Eric. D.},\n\tmonth = aug,\n\tyear = {2023},\n\tkeywords = {Burkitt lymphoma, Custom, Custom Cancer Panel, Diffuse large B-cell lymphoma/high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, High-grade B-cell lymphoma, High-grade B-cell lymphoma/large B-cell lymphoma with 11q aberration, Large B-cell lymphoma with IRF4 rearrangement},\n}\n\n

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\n \n\n \n \n \n \n \n \n Reliability of flow-cytometry in diagnosis and prognostic stratification of myelodysplastic syndromes: correlations with morphology and mutational profile.\n \n \n \n \n\n\n \n Guarnera, L.; Fabiani, E.; Attrotto, C.; Hajrullaj, H.; Cristiano, A.; Latagliata, R.; Fenu, S.; Buccisano, F.; Irno-Consalvo, M.; Conti, C.; Voso, M. T.; and Maurillo, L.\n\n\n \n\n\n\n Annals of Hematology. August 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Reliability$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{guarnera_reliability_2023,\n\ttitle = {Reliability of flow-cytometry in diagnosis and prognostic stratification of myelodysplastic syndromes: correlations with morphology and mutational profile},\n\tissn = {1432-0584},\n\tshorttitle = {Reliability of flow-cytometry in diagnosis and prognostic stratification of myelodysplastic syndromes},\n\turl = {https://doi.org/10.1007/s00277-023-05384-2},\n\tdoi = {10.1007/s00277-023-05384-2},\n\tabstract = {Diagnosis and prognostic stratification of myelodysplastic syndromes (MDS) have been complemented by new techniques, including flow cytometry and NGS. To analyze the relationship between molecular and cytofluorimetric data, we enrolled in this retrospective study, 145 patients, including 106 diagnosed with MDS and 39 controls. At disease onset, immunophenotypic (IF), cytogenetic tests, and cytomorphological (CM) examination on bone marrow were carried out in all patients, while NGS was performed in 58 cases. Ogata score presented a specificity of 100\\% and a sensitivity of 59\\%. The detection of at least two phenotypic aberrancies in Ogata negative patients increased the sensitivity to 83\\% and specificity to 87\\%. Correlations were identified between IF aberrancies and mutations, including positive Ogata{\\textgreater}2 and mutations in SRSF2 (p=0.035), CD15 and U2AF1 (0.032), CD56 and DNMT3A (p=0.042), and CD38 and TP53 (p=0.026). In multivariate analysis, U2AF1 mutations, associated with del(20q) and/or abnormalities of chromosome 7 (group 4 as defined by the EuroMDS score), significantly correlated with an inferior overall survival (p=0.019). These parameters and Ogata score{\\textgreater}2 also showed a significant correlation with inferior event-free survival (p=0.023 and p=0.041, respectively). Both CM and FC features correlated with prognosis and mutational patterns. In an integrated MDS work-up, these tools may guide indications for mutational screening for optimal risk stratification.},\n\tlanguage = {en},\n\turldate = {2023-08-25},\n\tjournal = {Annals of Hematology},\n\tauthor = {Guarnera, Luca and Fabiani, Emiliano and Attrotto, Cristina and Hajrullaj, Hajro and Cristiano, Antonio and Latagliata, Roberto and Fenu, Susanna and Buccisano, Francesco and Irno-Consalvo, Maria and Conti, Consuelo and Voso, Maria Teresa and Maurillo, Luca},\n\tmonth = aug,\n\tyear = {2023},\n\tkeywords = {Acute myeloid leukemia, Clonal disorders, DDM, MYS, Myelodysplastic syndromes},\n}\n\n

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\n \n\n \n \n \n \n \n \n Unexpected Inheritance Patterns in a Large Cohort of Patients with a Suspected Ciliopathy.\n \n \n \n \n\n\n \n Gouronc, A.; Javey, E.; Leuvrey, A.; Nourisson, E.; Friedmann, S.; Reichert, V.; Derive, N.; Francannet, C.; Keren, B.; Lévy, J.; Planes, M.; Ruaud, L.; Amiel, J.; Dollfus, H.; Scheidecker, S.; and Muller, J.\n\n\n \n\n\n\n Human Mutation, 2023: e2564200. August 2023.\n Publisher: Hindawi\n\n\n\n
\n\n\n\n \n \n $\"Unexpected$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{gouronc_unexpected_2023,\n\ttitle = {Unexpected {Inheritance} {Patterns} in a {Large} {Cohort} of {Patients} with a {Suspected} {Ciliopathy}},\n\tvolume = {2023},\n\turl = {https://www.hindawi.com/journals/humu/2023/2564200/},\n\tdoi = {10.1155/2023/2564200},\n\tabstract = {Ciliopathies are rare genetic disorders caused by dysfunction of the primary or motile cilia. Their mode of inheritance is mostly autosomal recessive with biallelic pathogenic variants inherited from the parents. However, exceptions exist such as uniparental disomy (UPD) or the appearance of a de novo pathogenic variant in trans of an inherited pathogenic variant. These two genetic mechanisms are expected to be extremely rare, and few data are available in the literature, especially regarding ciliopathies. In this study, we investigated 940 individuals (812 families) with a suspected ciliopathy by Sanger sequencing, high-throughput sequencing and/or SNP array analysis and performed a literature review of UPD and de novo variants in ciliopathies. In a large cohort of 623 individuals (511 families) with a molecular diagnosis of ciliopathy (mainly Bardet-Biedl syndrome and Alström syndrome), we identified five UPD, revealing an inherited pathogenic variant and five pathogenic variants of de novo appearance (in trans of another pathogenic variant). Moreover, from these ten cases, we reported 15 different pathogenic variants of which five are novel. We demonstrated a relatively high prevalence of UPD and de novo variants in a large cohort of ciliopathies and highlighted the importance of identifying such rare genetic events, especially for genetic counseling.},\n\tlanguage = {en},\n\turldate = {2023-08-25},\n\tjournal = {Human Mutation},\n\tauthor = {Gouronc, Aurélie and Javey, Elodie and Leuvrey, Anne-Sophie and Nourisson, Elsa and Friedmann, Sylvie and Reichert, Valérie and Derive, Nicolas and Francannet, Christine and Keren, Boris and Lévy, Jonathan and Planes, Marc and Ruaud, Lyse and Amiel, Jeanne and Dollfus, Hélène and Scheidecker, Sophie and Muller, Jean},\n\tmonth = aug,\n\tyear = {2023},\n\tnote = {Publisher: Hindawi},\n\tkeywords = {Alamut, Alamut Batch, Alamut Batch 1.1.0},\n\tpages = {e2564200},\n}\n\n

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\n \n\n \n \n \n \n \n \n Radiomics in the characterization of lipid-poor adrenal adenomas at unenhanced CT: time to look beyond usual density metrics.\n \n \n \n \n\n\n \n Feliciani, G.; Serra, F.; Menghi, E.; Ferroni, F.; Sarnelli, A.; Feo, C.; Zatelli, M. C.; Ambrosio, M. R.; Giganti, M.; and Carnevale, A.\n\n\n \n\n\n\n European Radiology. August 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Radiomics$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{feliciani_radiomics_2023,\n\ttitle = {Radiomics in the characterization of lipid-poor adrenal adenomas at unenhanced {CT}: time to look beyond usual density metrics},\n\tissn = {1432-1084},\n\tshorttitle = {Radiomics in the characterization of lipid-poor adrenal adenomas at unenhanced {CT}},\n\turl = {https://doi.org/10.1007/s00330-023-10090-8},\n\tdoi = {10.1007/s00330-023-10090-8},\n\tabstract = {In this study, we developed a radiomic signature for the classification of benign lipid-poor adenomas, which may potentially help clinicians limit the number of unnecessary investigations in clinical practice. Indeterminate adrenal lesions of benign and malignant nature may exhibit different values of key radiomics features.},\n\tlanguage = {en},\n\turldate = {2023-08-25},\n\tjournal = {European Radiology},\n\tauthor = {Feliciani, Giacomo and Serra, Francesco and Menghi, Enrico and Ferroni, Fabio and Sarnelli, Anna and Feo, Carlo and Zatelli, Maria Chiara and Ambrosio, Maria Rosaria and Giganti, Melchiore and Carnevale, Aldo},\n\tmonth = aug,\n\tyear = {2023},\n\tkeywords = {Abdomen, Adrenal incidentaloma, Adrenocortical adenoma, Artificial intelligence, Radiomics, X-ray computed tomography},\n}\n\n

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\n \n\n \n \n \n \n \n \n Novel α-1,3-Glucosyltransferase Variants and Their Broad Clinical Polycystic Liver Disease Spectrum.\n \n \n \n \n\n\n \n Boerrigter, M. M.; te Morsche, R. H. M.; Venselaar, H.; Pastoors, N.; Geerts, A. M.; Hoorens, A.; and Drenth, J. P. H.\n\n\n \n\n\n\n Genes, 14(8): 1652. August 2023.\n Number: 8 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Novel$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{boerrigter_novel_2023,\n\ttitle = {Novel α-1,3-{Glucosyltransferase} {Variants} and {Their} {Broad} {Clinical} {Polycystic} {Liver} {Disease} {Spectrum}},\n\tvolume = {14},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2073-4425},\n\turl = {https://www.mdpi.com/2073-4425/14/8/1652},\n\tdoi = {10.3390/genes14081652},\n\tabstract = {Protein-truncating variants in α-1,3-glucosyltransferase (ALG8) are a risk factor for a mild cystic kidney disease phenotype. The association between these variants and liver cysts is limited. We aim to identify pathogenic ALG8 variants in our cohort of autosomal dominant polycystic liver disease (ADPLD) individuals. In order to fine-map the phenotypical spectrum of pathogenic ALG8 variant carriers, we performed targeted ALG8 screening in 478 ADPLD singletons, and exome sequencing in 48 singletons and 4 patients from two large ADPLD families. Eight novel and one previously reported pathogenic variant in ALG8 were discovered in sixteen patients. The ALG8 clinical phenotype ranges from mild to severe polycystic liver disease, and from innumerable small to multiple large hepatic cysts. The presence of {\\textless}5 renal cysts that do not affect renal function is common in this population. Three-dimensional homology modeling demonstrated that six variants cause a truncated ALG8 protein with abnormal functioning, and one variant is predicted to destabilize ALG8. For the seventh variant, immunostaining of the liver tissue showed a complete loss of ALG8 in the cystic cells. ALG8-associated ADPLD has a broad clinical spectrum, including the possibility of developing a small number of renal cysts. This broadens the ADPLD genotype–phenotype spectrum and narrows the gap between liver-specific ADPLD and kidney-specific ADPKD.},\n\tlanguage = {en},\n\tnumber = {8},\n\turldate = {2023-08-25},\n\tjournal = {Genes},\n\tauthor = {Boerrigter, Melissa M. and te Morsche, René H. M. and Venselaar, Hanka and Pastoors, Nikki and Geerts, Anja M. and Hoorens, Anne and Drenth, Joost P. H.},\n\tmonth = aug,\n\tyear = {2023},\n\tnote = {Number: 8\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {ADPLD, ALG8, Alamut, Alamut Visual Plus, Alamut Visual Plus v.1.4, clinical spectrum, next-generation sequencing, polycystic liver disease},\n\tpages = {1652},\n}\n\n

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\n \n\n \n \n \n \n \n \n Impact of High-to-Moderate Penetrance Genes on Genetic Testing: Looking over Breast Cancer.\n \n \n \n \n\n\n \n Turchiano, A.; Piglionica, M.; Martino, S.; Bagnulo, R.; Garganese, A.; De Luisi, A.; Chirulli, S.; Iacoviello, M.; Stasi, M.; Tabaku, O.; Meneleo, E.; Capurso, M.; Crocetta, S.; Lattarulo, S.; Krylovska, Y.; Lastella, P.; Forleo, C.; Stella, A.; Bukvic, N.; Simone, C.; and Resta, N.\n\n\n \n\n\n\n Genes, 14(8): 1530. July 2023.\n Number: 8 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Impact$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{turchiano_impact_2023,\n\ttitle = {Impact of {High}-to-{Moderate} {Penetrance} {Genes} on {Genetic} {Testing}: {Looking} over {Breast} {Cancer}},\n\tvolume = {14},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2073-4425},\n\tshorttitle = {Impact of {High}-to-{Moderate} {Penetrance} {Genes} on {Genetic} {Testing}},\n\turl = {https://www.mdpi.com/2073-4425/14/8/1530},\n\tdoi = {10.3390/genes14081530},\n\tabstract = {Breast cancer (BC) is the most common cancer and the leading cause of cancer death in women worldwide. Since the discovery of the highly penetrant susceptibility genes BRCA1 and BRCA2, many other predisposition genes that confer a moderate risk of BC have been identified. Advances in multigene panel testing have allowed the simultaneous sequencing of BRCA1/2 with these genes in a cost-effective way. Germline DNA from 521 cases with BC fulfilling diagnostic criteria for hereditary BC were screened with multigene NGS testing. Pathogenic (PVs) and likely pathogenic (LPVs) variants in moderate penetrance genes were identified in 15 out of 521 patients (2.9\\%), including 2 missense, 7 non-sense, 1 indel, and 3 splice variants, as well as two different exon deletions, as follows: ATM (n = 4), CHEK2 (n = 5), PALB2 (n = 2), RAD51C (n = 1), and RAD51D (n = 3). Moreover, the segregation analysis of PVs and LPVs into first-degree relatives allowed the detection of CHEK2 variant carriers diagnosed with in situ melanoma and clear cell renal cell carcinoma (ccRCC), respectively. Extended testing beyond BRCA1/2 identified PVs and LPVs in a further 2.9\\% of BC patients. In conclusion, panel testing yields more accurate genetic information for appropriate counselling, risk management, and preventive options than assessing BRCA1/2 alone.},\n\tlanguage = {en},\n\tnumber = {8},\n\turldate = {2023-08-25},\n\tjournal = {Genes},\n\tauthor = {Turchiano, Antonella and Piglionica, Marilidia and Martino, Stefania and Bagnulo, Rosanna and Garganese, Antonella and De Luisi, Annunziata and Chirulli, Stefania and Iacoviello, Matteo and Stasi, Michele and Tabaku, Ornella and Meneleo, Eleonora and Capurso, Martina and Crocetta, Silvia and Lattarulo, Simone and Krylovska, Yevheniia and Lastella, Patrizia and Forleo, Cinzia and Stella, Alessandro and Bukvic, Nenad and Simone, Cristiano and Resta, Nicoletta},\n\tmonth = jul,\n\tyear = {2023},\n\tnote = {Number: 8\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {ATM, Alamut, Alamut Visual Plus, CHEK2, PALB2, RAD51C, RAD51D, breast cancer, moderate-penetrance genes},\n\tpages = {1530},\n}\n\n

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\n \n\n \n \n \n \n \n \n Implementation of DNA Methylation Array Profiling in Pediatric Central Nervous System Tumors: The AIM BRAIN Project: An Australian and New Zealand Children's Hematology and Oncology Group Study.\n \n \n \n \n\n\n \n White, C. L.; Kinross, K. M.; Buntine, M. K.; Rasouli, E.; Strong, R.; Jones, J. M.; Cain, J. E.; Sturm, D.; Sahm, F.; Jones, D. T. W.; Pfister, S. M.; Robertson, T.; D'Arcy, C.; Rodriguez, M. L.; Dyke, J. M.; Junckerstorff, R.; Bhuva, D. D.; Davis, M. J.; Wood, P.; Hassall, T.; Ziegler, D. S.; Kellie, S.; McCowage, G.; Alvaro, F.; Kirby, M.; Heath, J. A.; Tsui, K.; Dodgshun, A.; Eisenstat, D. D.; Khuong-Quang, D.; Wall, M.; Algar, E. M.; Gottardo, N. G.; and Hansford, J. R.\n\n\n \n\n\n\n The Journal of Molecular Diagnostics. July 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Implementation$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{white_implementation_2023,\n\ttitle = {Implementation of {DNA} {Methylation} {Array} {Profiling} in {Pediatric} {Central} {Nervous} {System} {Tumors}: {The} {AIM} {BRAIN} {Project}: {An} {Australian} and {New} {Zealand} {Children}'s {Hematology} and {Oncology} {Group} {Study}},\n\tissn = {1525-1578},\n\tshorttitle = {Implementation of {DNA} {Methylation} {Array} {Profiling} in {Pediatric} {Central} {Nervous} {System} {Tumors}},\n\turl = {https://www.sciencedirect.com/science/article/pii/S1525157823001575},\n\tdoi = {10.1016/j.jmoldx.2023.06.013},\n\tabstract = {DNA methylation array profiling for classifying pediatric central nervous system (CNS) tumors is a valuable adjunct to histopathology. However, unbiased prospective and interlaboratory validation studies have been lacking. The AIM BRAIN diagnostic trial involving 11 pediatric cancer centers in Australia and New Zealand was designed to test the feasibility of routine clinical testing and ran in parallel with the Molecular Neuropathology 2.0 (MNP2.0) study at Deutsches Krebsforschungszentrum (German Cancer Research Center). CNS tumors from 269 pediatric patients were prospectively tested on Illumina EPIC arrays, including 104 cases co-enrolled on MNP2.0. Using MNP classifier versions 11b4 and 12.5, we report classifications with a probability score ≥0.90 in 176 of 265 (66.4\\%) and 213 of 269 (79.2\\%) cases, respectively. Significant diagnostic information was obtained in 130 of 176 (74\\%) for 11b4, and 12 of 174 (7\\%) classifications were discordant with histopathology. Cases prospectively co-enrolled on MNP2.0 gave concordant classifications (99\\%) and score thresholds (93\\%), demonstrating excellent test reproducibility and sensitivity. Overall, DNA methylation profiling is a robust single workflow technique with an acceptable diagnostic yield that is considerably enhanced by the extensive subgroup and copy number profile information generated by the platform. The platform has excellent test reproducibility and sensitivity and contributes significantly to CNS tumor diagnosis.},\n\turldate = {2023-08-25},\n\tjournal = {The Journal of Molecular Diagnostics},\n\tauthor = {White, Christine L. and Kinross, Kathryn M. and Buntine, Molly K. and Rasouli, Elnaz and Strong, Robyn and Jones, Janelle M. and Cain, Jason E. and Sturm, Dominik and Sahm, Felix and Jones, David T. W. and Pfister, Stefan M. and Robertson, Thomas and D'Arcy, Colleen and Rodriguez, Michael L. and Dyke, Jason M. and Junckerstorff, Reimar and Bhuva, Dharmesh D. and Davis, Melissa J. and Wood, Paul and Hassall, Tim and Ziegler, David S. and Kellie, Stewart and McCowage, Geoffrey and Alvaro, Frank and Kirby, Maria and Heath, John A. and Tsui, Karen and Dodgshun, Andrew and Eisenstat, David D. and Khuong-Quang, Dong-Anh and Wall, Meaghan and Algar, Elizabeth M. and Gottardo, Nicholas G. and Hansford, Jordan R.},\n\tmonth = jul,\n\tyear = {2023},\n\tkeywords = {Custom, Custom Cancer Panel, DDM},\n}\n\n

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\n \n\n \n \n \n \n \n \n Correlation analysis between auto-immunological and mutational profiles in myelodysplastic syndromes.\n \n \n \n \n\n\n \n Cristiano, A.; Belardi, R.; Hajrullaj, H.; Fabiani, E.; Falconi, G.; Galossi, E.; Bernardini, S.; Voso, M. T.; and Nuccetelli, M.\n\n\n \n\n\n\n Inflammation Research. July 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Correlation$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{cristiano_correlation_2023,\n\ttitle = {Correlation analysis between auto-immunological and mutational profiles in myelodysplastic syndromes},\n\tissn = {1420-908X},\n\turl = {https://doi.org/10.1007/s00011-023-01773-5},\n\tdoi = {10.1007/s00011-023-01773-5},\n\tabstract = {Systemic-Inflammatory-Autoimmune-Diseases (SIAD) is increasingly considered in Myelodysplastic-Syndromes (MDS). In this line, we evaluated the MDS auto-immunological profile, correlating it to the mutational landscape, trying to identify a molecular-genetic trigger agent related to SIAD.},\n\tlanguage = {en},\n\turldate = {2023-08-25},\n\tjournal = {Inflammation Research},\n\tauthor = {Cristiano, Antonio and Belardi, Riccardo and Hajrullaj, Hajro and Fabiani, Emiliano and Falconi, Giulia and Galossi, Elisa and Bernardini, Sergio and Voso, Maria Teresa and Nuccetelli, Marzia},\n\tmonth = jul,\n\tyear = {2023},\n\tkeywords = {AML, ANA antigenic specificity, Anti-nuclear antibodies (ANA), Auto-immunological profile, DDM, Inflammatory and autoimmune diseases, MDS, MYS, Mutational profile, Myelodysplastic syndromes, VEXAS},\n}\n\n

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\n \n\n \n \n \n \n \n APC-Related Phenotypes and Intellectual Disability in 5q Interstitial Deletions: A New Case and Review of the Literature.\n \n \n \n\n\n \n Privitera, F.; Piccini, F.; Recalcati, M. P.; Presi, S.; Mazzola, S.; and Carrera, P.\n\n\n \n\n\n\n Genes, 14(7): 1505. July 2023.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{privitera_apc-related_2023,\n\ttitle = {{APC}-{Related} {Phenotypes} and {Intellectual} {Disability} in 5q {Interstitial} {Deletions}: {A} {New} {Case} and {Review} of the {Literature}},\n\tvolume = {14},\n\tissn = {2073-4425},\n\tshorttitle = {{APC}-{Related} {Phenotypes} and {Intellectual} {Disability} in 5q {Interstitial} {Deletions}},\n\tdoi = {10.3390/genes14071505},\n\tabstract = {The 5q deletion syndrome is a relatively rare condition caused by the monoallelic interstitial deletion of the long arm of chromosome 5. Patients described in literature usually present variable dysmorphic features, behavioral disturbance, and intellectual disability (ID); moreover, the involvement of the APC gene (5q22.2) in the deletion predisposes them to tumoral syndromes (Familial Adenomatous Polyposis and Gardner syndrome). Although the development of gastrointestinal tract malignancies has been extensively described, the genetic causes underlying neurologic manifestations have never been investigated. In this study, we described a new patient with a 19.85 Mb interstitial deletion identified by array-CGH and compared the deletions and the phenotypes reported in other patients already described in the literature and the Decipher database. Overlapping deletions allowed us to highlight a common region in 5q22.1q23.1, identifying KCNN2 (5q22.3) as the most likely candidate gene contributing to the neurologic phenotype.},\n\tlanguage = {eng},\n\tnumber = {7},\n\tjournal = {Genes},\n\tauthor = {Privitera, Flavia and Piccini, Flavia and Recalcati, Maria Paola and Presi, Silvia and Mazzola, Silvia and Carrera, Paola},\n\tmonth = jul,\n\tyear = {2023},\n\tpmid = {37510409},\n\tpmcid = {PMC10379344},\n\tkeywords = {5q deletion syndrome, Adenomatous Polyposis Coli Protein, Alamut, Alamut Visual Plus v.1.7, Chromosome Aberrations, Chromosome Deletion, Genes, APC, Humans, Intellectual Disability, KCNN2, Phenotype, array-CGH, intellectual disability},\n\tpages = {1505},\n}\n\n

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\n \n\n \n \n \n \n \n \n Genomic and Temporal Analysis of Deletions Correlated to qRT-PCR Dropout in N Gene in Alpha, Delta and Omicron Variants.\n \n \n \n \n\n\n \n Gatti, G.; Brandolini, M.; Mancini, A.; Taddei, F.; Zannoli, S.; Dirani, G.; Manera, M.; Arfilli, V.; Denicolò, A.; Marzucco, A.; Montanari, M. S.; Zaghi, I.; Guerra, M.; Tennina, R.; Marino, M. M.; Grumiro, L.; Cricca, M.; and Sambri, V.\n\n\n \n\n\n\n Viruses, 15(8): 1630. July 2023.\n Number: 8 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Genomic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{gatti_genomic_2023,\n\ttitle = {Genomic and {Temporal} {Analysis} of {Deletions} {Correlated} to {qRT}-{PCR} {Dropout} in {N} {Gene} in {Alpha}, {Delta} and {Omicron} {Variants}},\n\tvolume = {15},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {1999-4915},\n\turl = {https://www.mdpi.com/1999-4915/15/8/1630},\n\tdoi = {10.3390/v15081630},\n\tabstract = {Since the first SARS-CoV-2 outbreak, mutations such as single nucleotide polymorphisms (SNPs) and insertion/deletions (INDELs) have changed and characterized the viral genome sequence, structure and protein folding leading to the onset of new variants. The presence of those alterations challenges not only the clinical field but also the diagnostic demand due to failures in gene detection or incompleteness of polymerase chain reaction (PCR) results. In particular, the analysis of understudied genes such as N and the investigation through whole-genome next generation sequencing (WG-NGS) of regions more prone to mutate can help in the identification of new or reacquired mutations, with the aim of designing robust and long-lasting primers. In 48 samples of SARS-CoV-2 (including Alpha, Delta and Omicron variants), a lack of N gene amplification was observed in the genomes analyzed through WG-NGS. Three gene regions were detected hosting the highest number of SNPs and INDELs. In several cases, the latter can interfere deeply with both the sensitivity of diagnostic methodologies and the final protein folding. The monitoring over time of the viral evolution and the reacquisition among different variants of the same mutations or different alterations within the same genomic positions can be relevant to avoid unnecessary consumption of resources.},\n\tlanguage = {en},\n\tnumber = {8},\n\turldate = {2023-08-24},\n\tjournal = {Viruses},\n\tauthor = {Gatti, Giulia and Brandolini, Martina and Mancini, Andrea and Taddei, Francesca and Zannoli, Silvia and Dirani, Giorgio and Manera, Martina and Arfilli, Valentina and Denicolò, Agnese and Marzucco, Anna and Montanari, Maria Sofia and Zaghi, Irene and Guerra, Massimiliano and Tennina, Rita and Marino, Maria Michela and Grumiro, Laura and Cricca, Monica and Sambri, Vittorio},\n\tmonth = jul,\n\tyear = {2023},\n\tnote = {Number: 8\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {DDM, N gene, SARS-CoV-2, WG-NGS, deletions, gene dropout},\n\tpages = {1630},\n}\n\n

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\n \n\n \n \n \n \n \n Uncommon variants detected via hereditary cancer panel and suggestions for genetic counseling.\n \n \n \n\n\n \n Özdemir, Z.; Çevik, E.; Öksüzoğlu, Ö. B. Ç.; Doğan, M.; Ateş, Ö.; Esin, E.; Bilgetekin, İ.; Demirci, U.; Köseoğlu, Ç.; Topal, A.; Karadurmuş, N.; Erdem, H. B.; and Bahsi, T.\n\n\n \n\n\n\n Mutation Research, 827: 111831. July 2023.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{ozdemir_uncommon_2023,\n\ttitle = {Uncommon variants detected via hereditary cancer panel and suggestions for genetic counseling},\n\tvolume = {827},\n\tissn = {1873-135X},\n\tdoi = {10.1016/j.mrfmmm.2023.111831},\n\tabstract = {OBJECTIVE: Hereditary cancer syndromes constitute 5-10\\% of all cancers. The development of next-generation sequencing technologies has made it possible to examine many hereditary cancer syndrome-causing genes in a single panel. This study's goal was to describe the prevalence and the variant spectrum using NGS in individuals who were thought to have a hereditary predisposition for cancer.\nMATERIAL AND METHOD: Analysis was performed for 1254 who were thought to have a familial predisposition for cancer. We excluded 46 patients who were carrying BRCA1/2 variants in this study, for focusing on the rare gene mutations. Sequencing was performed using the Sophia Hereditary Cancer Solution v1.1 Panel and the Qiagen Large Hereditary Cancer Panel. The Illumina MiSeq system was used for the sequencing procedure. The software used for the data analyses was Sophia DDM and QIAGEN Clinical Insight (QCITM) Analyze. The resulting genomic changes were classified according to the current guidelines of ACMG/AMP.\nRESULTS: Pathogenic/likely pathogenic variants were detected in 172 (13.7\\%) of 1254 patients. After excluding the 46 BRCA1/2-positive patients, among the remaining 126 patients; there were 60 (4.8\\%) breast cancer, 33 (2.6\\%) colorectal cancer, 9 (0.7\\%) ovarian cancer, 5 (0.4\\%) endometrium cancer, 5 (0.4\\%) stomach cancer, 3 (0.2\\%) prostate cancer patients. The most altered genes were MUTYH in 27 (2.1\\%) patients, MMR genes (MLH1, MSH6, MSH, MSH2, PMS2 and EPCAM) in 26 (2\\%) patients, and ATM in 25 (2\\%) patients. We also examined the genotype-phenotype correlation in rare variants. Additionally, we identified 11 novel variations.\nCONCLUSION: This study provided significant information regarding rare variants observed in the Turkish population because it was carried out with a large patient group. Personalized treatment options and genetic counseling for the patients are therefore made facilitated.},\n\tlanguage = {eng},\n\tjournal = {Mutation Research},\n\tauthor = {Özdemir, Zeynep and Çevik, Ezgi and Öksüzoğlu, Ömür Berna Çakmak and Doğan, Mutlu and Ateş, Öztürk and Esin, Ece and Bilgetekin, İrem and Demirci, Umut and Köseoğlu, Çağlar and Topal, Alper and Karadurmuş, Nuri and Erdem, Haktan Bağış and Bahsi, Taha},\n\tmonth = jul,\n\tyear = {2023},\n\tpmid = {37453313},\n\tkeywords = {DDM, HCS, Hereditary cancer syndromes, Multigene panel testing, Next generation sequencing},\n\tpages = {111831},\n}\n\n

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\n \n\n \n \n \n \n \n High-throughput microfluidic blood testing to phenotype genetically linked platelet disorders: an aid to diagnosis.\n \n \n \n\n\n \n Fernández, D. I.; Provenzale, I.; Canault, M.; Fels, S.; Lenz, A.; Andresen, F.; Krümpel, A.; Dupuis, A.; Heemskerk, J. W. M.; Boeckelmann, D.; and Zieger, B. M. H.\n\n\n \n\n\n\n Blood Advances,bloodadvances.2023009860. June 2023.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{fernandez_high-throughput_2023,\n\ttitle = {High-throughput microfluidic blood testing to phenotype genetically linked platelet disorders: an aid to diagnosis},\n\tissn = {2473-9537},\n\tshorttitle = {High-throughput microfluidic blood testing to phenotype genetically linked platelet disorders},\n\tdoi = {10.1182/bloodadvances.2023009860},\n\tabstract = {Linking the genetic background of patients to a bleeding diathesis and altered platelet function is still challenging. We aimed to assess how the multiparameter microspot-based measurement of thrombus formation under flow can identify patients with a platelet bleeding disorder. For this purpose, we studied 16 patients, presenting with bleeding and/or albinism and a suspected platelet dysfunction, as well as 15 relatives. Genotyping of patients revealed a novel biallelic pathogenic variant in RASGRP2 (splice site c.240-1G{\\textgreater}A), abrogating CalDAG-GEFI expression; a compound heterozygosity (c.537del, c.571A{\\textgreater}T) in P2RY12, affecting P2Y12 signaling; and heterozygous variants of unknown significance in the P2RY12 and HPS3 genes. Other patients had confirmed Hermansky-Pudlak syndrome type 1 or 3. In 5 patients, no genetic variant was found. Platelet functions were assessed by routine laboratory measurements. Blood samples from all subjects and day controls were screened for blood cell counts and microfluidic outcome on six surfaces (48 parameters), in comparison to a reference cohort of healthy subjects. Differential analysis of the microfluidic data showed that key parameters of thrombus formation were compromised for the 16 index patients. Principal component analysis resulted in separate clusters of patients versus heterozygous family members plus control subjects. Clusters further segregated by inclusion of hematological values and laboratory measurements. Subject ranking indicated an overall impairment in thrombus formation for the patients carrying a (likely) pathogenic variant of the genes, but not for the asymptomatic relatives. Together, our results indicate the advantage of testing for multiparametric thrombus formation in this patient population.},\n\tlanguage = {eng},\n\tjournal = {Blood Advances},\n\tauthor = {Fernández, Delia Irene and Provenzale, Isabella and Canault, Matthias and Fels, Salome and Lenz, Antonia and Andresen, Felicia and Krümpel, Anne and Dupuis, Arnaud and Heemskerk, Johan W. M. and Boeckelmann, Doris and Zieger, Barbara Maria Hildegard},\n\tmonth = jun,\n\tyear = {2023},\n\tpmid = {37389831},\n\tkeywords = {Alamut, Alamut Visual Plus, Blood},\n\tpages = {bloodadvances.2023009860},\n}\n\n

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\n \n\n \n \n \n \n \n \n In Silico Copy Number Variation (CNVs) Bioinformatics Estimation: Dream or Nightmare?.\n \n \n \n \n\n\n \n Gutiérrez, L.; Parada-Fennen, L.; and Solano, A. R.\n\n\n \n\n\n\n EJIFCC, 34(1): 72–75. April 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"In$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{gutierrez_silico_2023,\n\ttitle = {In {Silico} {Copy} {Number} {Variation} ({CNVs}) {Bioinformatics} {Estimation}: {Dream} or {Nightmare}?},\n\tvolume = {34},\n\tissn = {1650-3414},\n\tshorttitle = {In {Silico} {Copy} {Number} {Variation} ({CNVs}) {Bioinformatics} {Estimation}},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10131236/},\n\tnumber = {1},\n\turldate = {2023-08-24},\n\tjournal = {EJIFCC},\n\tauthor = {Gutiérrez, Leandro and Parada-Fennen, Lara and Solano, Angela Rosaria},\n\tmonth = apr,\n\tyear = {2023},\n\tpmid = {37124656},\n\tpmcid = {PMC10131236},\n\tkeywords = {CE-IVD, DDM},\n\tpages = {72--75},\n}\n\n

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\n \n\n \n \n \n \n \n \n Primary cutaneous follicle centre lymphoma with secondary systemic evolution.\n \n \n \n \n\n\n \n Li, A.; Lehmann-Che, J.; Champ, J.; Rivet, J.; Vignon-Pennamen, M.; Mourah, S.; Cayuela, J.; Lepelletier, C.; Louveau, B.; Dumont, M.; Alhage, J.; Ram-Wolff, C.; Bouaziz, J.; Bagot, M.; De Masson, A.; and Battistella, M.\n\n\n \n\n\n\n JEADV Clinical Practice, n/a(n/a). June 2023.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/jvc2.186\n\n\n\n
\n\n\n\n \n \n $\"Primary$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{li_primary_2023,\n\ttitle = {Primary cutaneous follicle centre lymphoma with secondary systemic evolution},\n\tvolume = {n/a},\n\tcopyright = {© 2023 The Authors. JEADV Clinical Practice published by John Wiley \\& Sons Ltd on behalf of European Academy of Dermatology and Venereology.},\n\tissn = {2768-6566},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/jvc2.186},\n\tdoi = {10.1002/jvc2.186},\n\tabstract = {Primary cutaneous follicle centre lymphomas (PCFCLs) are cutaneous proliferation of centrocytes and centroblasts, with a generally indolent evolution. Secondary systemic spread of disease is a rare event, which significantly impairs prognosis. Recently published study by Zhou and al. proposed criteria aiming to predict such evolution at initial stage: (i) rearrangement of Bcl2, (ii) Ki67\\% index {\\textless}30\\% and (iii) 2 mutations among the CREBBP, KMT2D, EZH2 and EP300.1 genes. We herein report two cases of PCFCLs with systemic evolution. Both patients had been initially diagnosed with localised skin disease, and developed, several years after, a secondary systemic involvement. Skin biopsies at the initial stage and systemic spread were analysed by histology, immunohistochemistry, fluorescence in situ hybridisation, and by DNA sequencing of a panel of 54 genes frequently mutated in lymphomas. Both patients showed no rearrangement of Bcl2, {\\textgreater}30\\% Ki67\\% indexes and no mutations among the four proposed genes. These findings run contrary to these previously proposed criteria, highlighting the molecular heterogeneity of this rare disease.},\n\tlanguage = {en},\n\tnumber = {n/a},\n\turldate = {2023-08-24},\n\tjournal = {JEADV Clinical Practice},\n\tauthor = {Li, Andy and Lehmann-Che, Jacqueline and Champ, Jérôme and Rivet, Jacqueline and Vignon-Pennamen, Marie-Dominique and Mourah, Samia and Cayuela, Jean-Michel and Lepelletier, Clémence and Louveau, Baptiste and Dumont, Maëlle and Alhage, Jana and Ram-Wolff, Caroline and Bouaziz, Jean-David and Bagot, Martine and De Masson, Adèle and Battistella, Maxime},\n\tmonth = jun,\n\tyear = {2023},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/jvc2.186},\n\tkeywords = {B-cell lymphoma, LYS, Lymphoma, Lymphoma solution, cutaneous follicle centre lymphoma, cutaneous lymphoma},\n}\n\n

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\n \n\n \n \n \n \n \n \n Identification and interpretation of TET2 noncanonical splicing site intronic variants in myeloid neoplasm patients.\n \n \n \n \n\n\n \n Das, R.; Tu, Z. J.; Bosler, D. S.; and Cheng, Y.\n\n\n \n\n\n\n eJHaem, 4(3): 738–744. June 2023.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/jha2.744\n\n\n\n
\n\n\n\n \n \n $\"Identification$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{das_identification_2023,\n\ttitle = {Identification and interpretation of {TET2} noncanonical splicing site intronic variants in myeloid neoplasm patients},\n\tvolume = {4},\n\tcopyright = {© 2023 The Authors. eJHaem published by British Society for Haematology and John Wiley \\& Sons Ltd.},\n\tissn = {2688-6146},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/jha2.744},\n\tdoi = {10.1002/jha2.744},\n\tabstract = {Background: DNA hypermethylation and instability due to inactivation mutations in Ten–eleven translocation 2 (TET2) is a key biomarker of hematological malignancies. This study aims at characterizing two intronic noncanonical splice-site variants, c.3954+5\\_3954+8delGTTT and c.3954+5G{\\textgreater}A. Methods: We used in silico prediction tools, reverse transcription (RT)-PCR, and Sanger sequencing on blood/bone marrow-derived RNA specimens to determine the aberrant splicing. Results: In silico prediction of both variants exhibited reduced splicing strength at the TET2 intron 7 splicing donor site. RT-PCR and Sanger sequencing identified a 62-bp deletion at the exon 7, producing a frameshift mutation, p.Cys1298*. Conclusion: This study provides functional evidence for two intronic TET2 variants that cause alternative splicing and frameshift mutation.},\n\tlanguage = {en},\n\tnumber = {3},\n\turldate = {2023-08-24},\n\tjournal = {eJHaem},\n\tauthor = {Das, Riku and Tu, Zheng Jin and Bosler, David S. and Cheng, Yu-Wei},\n\tmonth = jun,\n\tyear = {2023},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/jha2.744},\n\tkeywords = {Alamut, Alamut Visual Plus, Alamut Visual Plus v.1.3, TET2, in silico prediction, myeloid neoplasm, next-generation sequencing (NGS), noncanonical splicing site, ten-eleven translocation 2, tumor suppressor},\n\tpages = {738--744},\n}\n\n

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\n \n\n \n \n \n \n \n \n P042: A next generation sequencing strategy for a comprehensive molecular diagnosis in chronic lymphocytic leukemia: Mexican experience.\n \n \n \n \n\n\n \n Abreu, M.; Martínez, L. V.; Ceballos López, A. A.; Prieto, A. V.; García, Á. C.; Court, M. D.; Amatón Tabares, R. P.; Carvajal Lohr, S. M.; Galindo Ruvalcaba, C. H.; Hernández, F. G.; Rodríguez Muñoz, Y. F.; Ancheyta, L. H.; and Azotla Vilchis, C. O.\n\n\n \n\n\n\n Genetics in Medicine Open, 1(1): 100061. March 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"P042:$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{abreu_p042_2023,\n\ttitle = {P042: {A} next generation sequencing strategy for a comprehensive molecular diagnosis in chronic lymphocytic leukemia: {Mexican} experience},\n\tvolume = {1},\n\tissn = {29497744},\n\tshorttitle = {P042},\n\turl = {https://linkinghub.elsevier.com/retrieve/pii/S2949774423000614},\n\tdoi = {10.1016/j.gimo.2023.100061},\n\tabstract = {Introduction: Chronic lymphocytic leukemia (CLL) is a heterogeneous disease, being the most common leukemia in adults in Western countries (30\\%), however is very rare in Asia and Latin America, including Mexico (7\\% in Mexican Mestizos). Although the different prevalence around populations, the clinical and molecular features of the disease are quite similar, with recurrent chromosomal abnormalities such as deletions in 13q14 (50\\%-60\\%), 11q (15\\%), 17p (10\\%) and trisomy 12 (15\\%). The most frequent gene variants occur in SF3B1 (10–15\\%) and NOTCH1 ({\\textasciitilde}10\\%). Current prognostic and predictive biomarkers in patients with CLL are pathogenic variants in TP53, deletions in 17p and the mutational status of the immunoglobulin heavy-chain variable region (IGHV). As the genetic proﬁle of CLL is complex and multiple concurrent genetic variants are present, a comprehensive cost/effective NGS test was chosen to detect the informative genetic abnormalities in a cohort of 31 Mexican patients with CLL in different stages of treatment or follow up.\nMethods: Thirty-one CLL Mexican patients were clinical selected (monoclonal B lymphocytes ≥5 x 109/L with clonality of B cells conﬁrmed by ﬂow cytometry). NGS was performed using Sophia Genetics® CLL\\_V2 Custom panel that targets 15 genes: ATM, BIRC3, CXCR4, EGR2, FBXW7, KRAS, MYD88, NFKBIE, POT1 and TP53, as well as hotspots in BTK, NOTCH1, PLG2, SF3B1 and XPO1. This kit identiﬁes for {\\textgreater}20\\% of cellular content copy number variants (CNVs) in KRAS, ATF1 and CDK4 (for trisomy 12); DLEU1, PROZ, KLF5, and CUL4A (for 13q deletion), ATM and TP53. For the bioinformatic analysis, the Sophia DDM® software was used and variants were classiﬁed as pathogenic/probably pathogenic according to ACMG guidelines (allelic frequency ≥5\\%). The analysis of the IG gene was performed from FASTQ ﬁles using the IgCaller Web and IMGT/V-QUEST software, where the IGHV is considered unmutated (IGHV-UM) if the identity with the germinal sequence is ≥98\\%.\nResults: A total of 31 patients were analyzed: 15 females and 16 males. 55\\% of the cases were from the northern part of the country (n=17), of which Sonora has the highest incidence with 11 cases (65\\%). At the time of the genetic analysis, only 6 patients (19\\%) were undergoing treatment, where 4 used BTK inhibitors and 2 chemotherapy. A biomarker with prognostic value was identiﬁed in 87\\% of the patients; 11/31 presented IGHV-UM, of which 73\\% of the cases were accompanied by at least one other genetic alteration (SNV or CNV) and 45\\% by two concomitant alterations. 13\\% of the patients had trisomy 12 and all were accompanied by an IGHV-UM. In 2/6 patients who were on treatment, an IGHV-UM and/or a pathogenic variant in TP53 was detected.\nConclusion: The distribution and frequency of CLL in the north of Mexico is probably related to a greater European genetic contribution in this part of the country and this cohort shows a selective high incidence in this region, particularly Sonora. This all-in-one genomic strategy allows a comprehensive detection of the principal known and new prognostic CLL gene associations, CNV detection and IGHV mutational status, making possible to optimize time and economic resources in the management of CLL patients, which is extremely important in lowincome countries. Also, these broad genomic panel have made it possible to ﬁnd new associations of prognostic value in CLL, as appears to be trisomy 12 in Mexican patients who are been detected with IGHV-UM, having a worse prognosis.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2023-05-10},\n\tjournal = {Genetics in Medicine Open},\n\tauthor = {Abreu, Melania and Martínez, Luis Villela and Ceballos López, Adrián Alejandro and Prieto, Alberto Villalobos and García, Álvaro Cabrera and Court, Marcela Deffis and Amatón Tabares, René Porfirio and Carvajal Lohr, Siria María and Galindo Ruvalcaba, Cesar Humberto and Hernández, Federico Godínez and Rodríguez Muñoz, Yolanda Fabiola and Ancheyta, Lizbeth Hernández and Azotla Vilchis, Coztli Ocelotl},\n\tmonth = mar,\n\tyear = {2023},\n\tkeywords = {CLL, CLL v2, Chronic lymphocytic leukaemia, Custom Panel, DDM},\n\tpages = {100061},\n}\n\n

\n\n\n

\n Introduction: Chronic lymphocytic leukemia (CLL) is a heterogeneous disease, being the most common leukemia in adults in Western countries (30%), however is very rare in Asia and Latin America, including Mexico (7% in Mexican Mestizos). Although the different prevalence around populations, the clinical and molecular features of the disease are quite similar, with recurrent chromosomal abnormalities such as deletions in 13q14 (50%-60%), 11q (15%), 17p (10%) and trisomy 12 (15%). The most frequent gene variants occur in SF3B1 (10–15%) and NOTCH1 (~10%). Current prognostic and predictive biomarkers in patients with CLL are pathogenic variants in TP53, deletions in 17p and the mutational status of the immunoglobulin heavy-chain variable region (IGHV). As the genetic proﬁle of CLL is complex and multiple concurrent genetic variants are present, a comprehensive cost/effective NGS test was chosen to detect the informative genetic abnormalities in a cohort of 31 Mexican patients with CLL in different stages of treatment or follow up. Methods: Thirty-one CLL Mexican patients were clinical selected (monoclonal B lymphocytes ≥5 x 109/L with clonality of B cells conﬁrmed by ﬂow cytometry). NGS was performed using Sophia Genetics® CLL_V2 Custom panel that targets 15 genes: ATM, BIRC3, CXCR4, EGR2, FBXW7, KRAS, MYD88, NFKBIE, POT1 and TP53, as well as hotspots in BTK, NOTCH1, PLG2, SF3B1 and XPO1. This kit identiﬁes for \\textgreater20% of cellular content copy number variants (CNVs) in KRAS, ATF1 and CDK4 (for trisomy 12); DLEU1, PROZ, KLF5, and CUL4A (for 13q deletion), ATM and TP53. For the bioinformatic analysis, the Sophia DDM® software was used and variants were classiﬁed as pathogenic/probably pathogenic according to ACMG guidelines (allelic frequency ≥5%). The analysis of the IG gene was performed from FASTQ ﬁles using the IgCaller Web and IMGT/V-QUEST software, where the IGHV is considered unmutated (IGHV-UM) if the identity with the germinal sequence is ≥98%. Results: A total of 31 patients were analyzed: 15 females and 16 males. 55% of the cases were from the northern part of the country (n=17), of which Sonora has the highest incidence with 11 cases (65%). At the time of the genetic analysis, only 6 patients (19%) were undergoing treatment, where 4 used BTK inhibitors and 2 chemotherapy. A biomarker with prognostic value was identiﬁed in 87% of the patients; 11/31 presented IGHV-UM, of which 73% of the cases were accompanied by at least one other genetic alteration (SNV or CNV) and 45% by two concomitant alterations. 13% of the patients had trisomy 12 and all were accompanied by an IGHV-UM. In 2/6 patients who were on treatment, an IGHV-UM and/or a pathogenic variant in TP53 was detected. Conclusion: The distribution and frequency of CLL in the north of Mexico is probably related to a greater European genetic contribution in this part of the country and this cohort shows a selective high incidence in this region, particularly Sonora. This all-in-one genomic strategy allows a comprehensive detection of the principal known and new prognostic CLL gene associations, CNV detection and IGHV mutational status, making possible to optimize time and economic resources in the management of CLL patients, which is extremely important in lowincome countries. Also, these broad genomic panel have made it possible to ﬁnd new associations of prognostic value in CLL, as appears to be trisomy 12 in Mexican patients who are been detected with IGHV-UM, having a worse prognosis.\n

\n\n\n

\n \n\n \n \n \n \n \n \n Measurable Residual Disease and Clonal Evolution in Acute Myeloid Leukemia from Diagnosis to Post-transplant Follow-Up: The Role of Next-Generation Sequencing.\n \n \n \n \n\n\n \n Sperotto, A.; Bochicchio, M. T.; Simonetti, G.; Buccisano, F.; Peccatori, J.; Piemontese, S.; Calistri, E.; Ciotti, G.; Pierdomenico, E.; De Marchi, R.; Ciceri, F.; and Gottardi, M.\n\n\n \n\n\n\n Biomedicines, 11(2): 359. January 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Measurable$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{sperotto_measurable_2023,\n\ttitle = {Measurable {Residual} {Disease} and {Clonal} {Evolution} in {Acute} {Myeloid} {Leukemia} from {Diagnosis} to {Post}-transplant {Follow}-{Up}: {The} {Role} of {Next}-{Generation} {Sequencing}},\n\tvolume = {11},\n\tissn = {2227-9059},\n\tshorttitle = {Measurable {Residual} {Disease} and {Clonal} {Evolution} in {Acute} {Myeloid} {Leukemia} from {Diagnosis} to {Post}-transplant {Follow}-{Up}},\n\turl = {https://www.mdpi.com/2227-9059/11/2/359},\n\tdoi = {10.3390/biomedicines11020359},\n\tabstract = {It has now been ascertained that acute myeloid leukemias—as in most type of cancers—are mixtures of various subclones, evolving by acquiring additional somatic mutations over the course of the disease. The complexity of leukemia clone architecture and the phenotypic and/or genotypic drifts that can occur during treatment explain why more than 50\\% of patients—in hematological remission—could relapse. Moreover, the complexity and heterogeneity of clone architecture represent a hindrance for monitoring measurable residual disease, as not all minimal residual disease monitoring methods are able to detect genetic mutations arising during treatment. Unlike with chemotherapy, which imparts a relatively short duration of selective pressure on acute myeloid leukemia clonal architecture, the immunological effect related to allogeneic hematopoietic stem cell transplant is prolonged over time and must be overcome for relapse to occur. This means that not all molecular abnormalities detected after transplant always imply inevitable relapse. Therefore, transplant represents a critical setting where a measurable residual disease-based strategy, performed during post-transplant follow-up by highly sensitive methods such as next-generation sequencing, could optimize and improve treatment outcome. The purpose of our review is to provide an overview of the role of next-generation sequencing in monitoring both measurable residual disease and clonal evolution in acute myeloid leukemia patients during the entire course of the disease, with special focus on the transplant phase.},\n\tlanguage = {en},\n\tnumber = {2},\n\turldate = {2023-02-08},\n\tjournal = {Biomedicines},\n\tauthor = {Sperotto, Alessandra and Bochicchio, Maria Teresa and Simonetti, Giorgia and Buccisano, Francesco and Peccatori, Jacopo and Piemontese, Simona and Calistri, Elisabetta and Ciotti, Giulia and Pierdomenico, Elisabetta and De Marchi, Roberta and Ciceri, Fabio and Gottardi, Michele},\n\tmonth = jan,\n\tyear = {2023},\n\tkeywords = {Extended Myeloid Solution, Myeloid, Myeloid Plus, next-generation sequencing},\n\tpages = {359},\n}\n\n

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\n \n\n \n \n \n \n \n \n Detection of germline variants with pathogenic potential in 48 patients with familial colorectal cancer by using whole exome sequencing.\n \n \n \n \n\n\n \n Singh, A. K.; Talseth-Palmer, B.; Xavier, A.; Scott, R. J.; Drabløs, F.; and Sjursen, W.\n\n\n \n\n\n\n BMC Medical Genomics, 16(1): 126. June 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Detection$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{singh_detection_2023,\n\ttitle = {Detection of germline variants with pathogenic potential in 48 patients with familial colorectal cancer by using whole exome sequencing},\n\tvolume = {16},\n\tissn = {1755-8794},\n\turl = {https://doi.org/10.1186/s12920-023-01562-3},\n\tdoi = {10.1186/s12920-023-01562-3},\n\tabstract = {Hereditary genetic mutations causing predisposition to colorectal cancer are accountable for approximately 30\\% of all colorectal cancer cases. However, only a small fraction of these are high penetrant mutations occurring in DNA mismatch repair genes, causing one of several types of familial colorectal cancer (CRC) syndromes. Most of the mutations are low-penetrant variants, contributing to an increased risk of familial colorectal cancer, and they are often found in additional genes and pathways not previously associated with CRC. The aim of this study was to identify such variants, both high-penetrant and low-penetrant ones.},\n\tnumber = {1},\n\turldate = {2023-08-24},\n\tjournal = {BMC Medical Genomics},\n\tauthor = {Singh, Ashish Kumar and Talseth-Palmer, Bente and Xavier, Alexandre and Scott, Rodney J. and Drabløs, Finn and Sjursen, Wenche},\n\tmonth = jun,\n\tyear = {2023},\n\tkeywords = {Alamut, Alamut Visual Plus, Alamut v.1.6.1, Colorectal cancer (CRC), Copy number variation (CNV), Familial colorectal cancer Type X (FCCTX), Lynch syndrome (LS), Mismatch repair (MMR), Variant annotation, Variant filtration, Whole exome sequencing (WES)},\n\tpages = {126},\n}\n\n

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\n \n\n \n \n \n \n \n \n IMPDH1 -associated autosomal dominant retinitis pigmentosa: natural history of novel variant Lys3124Gln and a comprehensive literature search.\n \n \n \n \n\n\n \n Sakti, D. H.; Cornish, E. E.; Nash, B. M.; Jamieson, R. V.; and Grigg, J. R.\n\n\n \n\n\n\n Ophthalmic Genetics,1–19. May 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"<i>IMPDH1</i>$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{sakti_impdh1_2023,\n\ttitle = {\\textit{{IMPDH1}} -associated autosomal dominant retinitis pigmentosa: natural history of novel variant {Lys3124Gln} and a comprehensive literature search},\n\tissn = {1381-6810, 1744-5094},\n\tshorttitle = {\\textit{{IMPDH1}} -associated autosomal dominant retinitis pigmentosa},\n\turl = {https://www.tandfonline.com/doi/full/10.1080/13816810.2023.2215310},\n\tdoi = {10.1080/13816810.2023.2215310},\n\tlanguage = {en},\n\turldate = {2023-06-16},\n\tjournal = {Ophthalmic Genetics},\n\tauthor = {Sakti, Dhimas H. and Cornish, Elisa E. and Nash, Benjamin M. and Jamieson, Robyn V. and Grigg, John R.},\n\tmonth = may,\n\tyear = {2023},\n\tkeywords = {Alamut, Alamut Visual Plus v1.6.1},\n\tpages = {1--19},\n}\n\n

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\n \n\n \n \n \n \n \n \n Benefits of applying molecular barcoding systems are not uniform across different genomic applications.\n \n \n \n \n\n\n \n Bieler, J.; Kubik, S.; Macheret, M.; Pozzorini, C.; Willig, A.; and Xu, Z.\n\n\n \n\n\n\n Journal of Translational Medicine, 21(1): 305. May 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Benefits$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{bieler_benefits_2023,\n\ttitle = {Benefits of applying molecular barcoding systems are not uniform across different genomic applications},\n\tvolume = {21},\n\tissn = {1479-5876},\n\turl = {https://doi.org/10.1186/s12967-023-04160-0},\n\tdoi = {10.1186/s12967-023-04160-0},\n\tabstract = {Despite the wide variety of Next Generation Sequencing (NGS)-based methods, it remains challenging to detect mutations present at very low frequencies. This problem is particularly relevant in oncology, where the limiting amount of input material, and its low quality, often limit the performance of the assays. Unique Molecular Identifiers (UMIs) are a molecular barcoding system often coupled with computational methods of noise suppression to improve the reliability of detection of rare variants. Although widely adopted, UMI inclusion imposes additional technical complexity and sequencing cost. Currently, there are no guidelines on UMI usage nor a comprehensive evaluation of their advantage across different applications.},\n\tnumber = {1},\n\turldate = {2023-06-16},\n\tjournal = {Journal of Translational Medicine},\n\tauthor = {Bieler, Jonathan and Kubik, Slawomir and Macheret, Morgane and Pozzorini, Christian and Willig, Adrian and Xu, Zhenyu},\n\tmonth = may,\n\tyear = {2023},\n\tkeywords = {UMI, UMIs General, Unique molecular identifier},\n\tpages = {305},\n}\n\n

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\n \n\n \n \n \n \n \n \n Reduced cone photoreceptor function and subtle systemic manifestations in two siblings with loss of SCLT1.\n \n \n \n \n\n\n \n Grudzinska Pechhacker, M. K; Molnar, A.; Pekkola Pacheco, N.; Thonberg, H.; Querat, L.; Birkeldh, U.; Nordgren, A.; and Lindstrand, A.\n\n\n \n\n\n\n Ophthalmic Genetics,1–8. May 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Reduced$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{grudzinska_pechhacker_reduced_2023,\n\ttitle = {Reduced cone photoreceptor function and subtle systemic manifestations in two siblings with loss of {SCLT1}},\n\tissn = {1381-6810, 1744-5094},\n\turl = {https://www.tandfonline.com/doi/full/10.1080/13816810.2023.2215332},\n\tdoi = {10.1080/13816810.2023.2215332},\n\tlanguage = {en},\n\turldate = {2023-06-16},\n\tjournal = {Ophthalmic Genetics},\n\tauthor = {Grudzinska Pechhacker, Monika K and Molnar, Anna and Pekkola Pacheco, Nadja and Thonberg, Håkan and Querat, Laurence and Birkeldh, Ulrika and Nordgren, Ann and Lindstrand, Anna},\n\tmonth = may,\n\tyear = {2023},\n\tkeywords = {Alamut Visual Plus, Alamut Visual Plus v.1.2},\n\tpages = {1--8},\n}\n\n

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\n \n\n \n \n \n \n \n \n NOTCH3 Variants in Patients with Suspected CADASIL.\n \n \n \n \n\n\n \n Gorukmez, O.; Gorukmez, O.; Topak, A.; Seferoglu, M.; Sivaci, A. O.; Ali, A.; Tepe, N.; Kabay, S. C.; and Taskapılıoglu, O.\n\n\n \n\n\n\n Annals of Indian Academy of Neurology. May 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"NOTCH3$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{gorukmez_notch3_2023,\n\ttitle = {{NOTCH3} {Variants} in {Patients} with {Suspected} {CADASIL}},\n\tissn = {0972-2327},\n\turl = {https://journals.lww.com/annalsofian/Abstract/9000/NOTCH3_Variants_in_Patients_with_Suspected_CADASIL.99962.aspx},\n\tdoi = {10.4103/aian.aian_989_22},\n\tabstract = {Background: \n          Cerebral autosomal dominant arteriopathy with subcortical infarctions and leukoencephalopathy (CADASIL) is the most common hereditary form of cerebral small vessel disease. It is clinically, radiologically, and genetically heterogeneous and is caused by NOTCH3 mutations.\n          Methods: \n          In this study, we analyzed NOTCH3 in 368 patients with suspected CADASIL using next-generation sequencing. The significant variants detected were reported along with the clinical and radiological features of the patients.\n          Results: \n          Heterozygous NOTCH3 changes, mostly missense mutations, were detected in 44 of the 368 patients ({\\textasciitilde}12\\%).\n          Conclusions: \n          In this single-center study conducted on a large patient group, 30 different variants were detected, 17 of which were novel. CADASIL, which can result in mortality, has a heterogeneous phenotype among individuals in terms of clinical, demographic, and radiological findings regardless of the NOTCH3 variant.},\n\tlanguage = {en-US},\n\turldate = {2023-06-16},\n\tjournal = {Annals of Indian Academy of Neurology},\n\tauthor = {Gorukmez, Orhan and Gorukmez, Ozlem and Topak, Ali and Seferoglu, Meral and Sivaci, Ali O. and Ali, Asuman and Tepe, Nermin and Kabay, Sibel C. and Taskapılıoglu, Ozlem},\n\tmonth = may,\n\tyear = {2023},\n\tkeywords = {DDM},\n}\n\n

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\n \n\n \n \n \n \n \n \n PIK3CA mutations in breast cancer: A Tunisian series.\n \n \n \n \n\n\n \n Rekaya, M. B.; Sassi, F.; Saied, E.; Kacem, L. B. H.; Mansouri, N.; Zarrouk, S.; Azouz, S.; and Rammeh, S.\n\n\n \n\n\n\n PLOS ONE, 18(5): e0285413. May 2023.\n Publisher: Public Library of Science\n\n\n\n
\n\n\n\n \n \n $\"PIK3CA$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{rekaya_pik3ca_2023,\n\ttitle = {{PIK3CA} mutations in breast cancer: {A} {Tunisian} series},\n\tvolume = {18},\n\tissn = {1932-6203},\n\tshorttitle = {{PIK3CA} mutations in breast cancer},\n\turl = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0285413},\n\tdoi = {10.1371/journal.pone.0285413},\n\tabstract = {Background The aim of this study was to analyze PIK3CA mutations in exons 9 and 20 in breast cancers (BCs) and their association with clinicopathological characteristics. Methods Mutational analysis of PIK3CA exon 9 and 20 was performed by Sanger sequencing in 54 primary BCs of Tunisian women. The associations of PIK3CA mutations with clinicopathological characteristics were analyzed. Results Fifteen exon 9 and exon 20 PIK3CA variants were identified in 33/54 cases (61\\%). PIK3CA mutations including pathogenic (class 5/Tier I) or likely pathogenic (class 4/Tier II) occurred in 24/54 cases (44\\%): 17/24 cases (71\\%) in exon 9, 5/24 cases (21\\%) in exon 20 and 2/24 cases (8\\%) in both exons. Of these 24 cases, 18 (75\\%) carried at least one of the three hot spot mutations: E545K (in 8 cases), H1047R (in 4 cases), E542K (in 3 cases), E545K/E542K (in one case), E545K/H1047R (in one case) and P539R/H1047R (in one case). Pathogenic PIK3CA mutations were associated with negative lymph node status (p = 0.027). Age distribution, histological SBR tumor grading, estrogen and progesterone receptors, human epidermal growth factor receptor 2, and molecular classification were not correlated with PIK3CA mutations (p {\\textgreater} 0.05). Conclusion The frequency of somatic PIK3CA mutations in BCs of Tunisian women is slightly higher than that of BCs of Caucasian women and more observed in exon 9 than in exon 20. PIK3CA mutated status is associated with negative lymph node status. These data need to be confirmed in larger series.},\n\tlanguage = {en},\n\tnumber = {5},\n\turldate = {2023-06-16},\n\tjournal = {PLOS ONE},\n\tauthor = {Rekaya, Mariem Ben and Sassi, Farah and Saied, Essya and Kacem, Linda Bel Haj and Mansouri, Nada and Zarrouk, Sinda and Azouz, Saifeddine and Rammeh, Soumaya},\n\tmonth = may,\n\tyear = {2023},\n\tnote = {Publisher: Public Library of Science},\n\tkeywords = {Alamut Plus, Breast cancer},\n\tpages = {e0285413},\n}\n\n

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\n \n\n \n \n \n \n \n \n Hereditary Gastric Cancer: Single-Gene or Multigene Panel Testing? A Mono-Institutional Experience.\n \n \n \n \n\n\n \n Calvello, M.; Marabelli, M.; Gandini, S.; Marino, E.; Bernard, L.; Dal Molin, M.; Di Cola, G.; Zanzottera, C.; Corso, G.; Fazio, N.; Gervaso, L.; Fumagalli Romario, U.; Barberis, M.; Guerrieri-Gonzaga, A.; Bertario, L.; Serrano, D.; and Bonanni, B.\n\n\n \n\n\n\n Genes, 14(5): 1077. May 2023.\n Number: 5 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Hereditary$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{calvello_hereditary_2023,\n\ttitle = {Hereditary {Gastric} {Cancer}: {Single}-{Gene} or {Multigene} {Panel} {Testing}? {A} {Mono}-{Institutional} {Experience}},\n\tvolume = {14},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2073-4425},\n\tshorttitle = {Hereditary {Gastric} {Cancer}},\n\turl = {https://www.mdpi.com/2073-4425/14/5/1077},\n\tdoi = {10.3390/genes14051077},\n\tabstract = {Gastric cancer (GC) has long been a ‘Cinderella’ among hereditary cancers. Until recently, single-gene testing (SGT) was the only approach to identify high-risk individuals. With the spread of multigene panel testing (MGPT), a debate arose on the involvement of other genes, particularly those pertaining to homologous recombination (HR) repair. We report our mono-institutional experience in genetic counseling and SGT for 54 GC patients, with the detection of nine pathogenic variants (PVs) (9/54:16.7\\%). Seven out of fifty (14\\%) patients who underwent SGT for unknown mutations were carriers of a PV in CDH1 (n = 3), BRCA2 (n = 2), BRCA1 (n = 1), and MSH2 (n = 1), while one patient (2\\%) carried two variants of unknown significance (VUSs). CDH1 and MSH2 emerged as genes involved in early-onset diffuse and later-onset intestinal GCs, respectively. We additionally conducted MGPT on 37 patients, identifying five PVs (13.5\\%), including three (3/5:60\\%) in an HR gene (BRCA2, ATM, RAD51D) and at least one VUS in 13 patients (35.1\\%). Comparing PV carriers and non-carriers, we observed a statistically significant difference in PVs between patients with and without family history of GC (p-value: 0.045) or Lynch-related tumors (p-value: 0.036). Genetic counseling remains central to GC risk assessment. MGPT appeared advantageous in patients with unspecific phenotypes, although it led to challenging results.},\n\tlanguage = {en},\n\tnumber = {5},\n\turldate = {2023-06-16},\n\tjournal = {Genes},\n\tauthor = {Calvello, Mariarosaria and Marabelli, Monica and Gandini, Sara and Marino, Elena and Bernard, Loris and Dal Molin, Matteo and Di Cola, Giulia and Zanzottera, Cristina and Corso, Giovanni and Fazio, Nicola and Gervaso, Lorenzo and Fumagalli Romario, Uberto and Barberis, Massimo and Guerrieri-Gonzaga, Aliana and Bertario, Lucio and Serrano, Davide and Bonanni, Bernardo},\n\tmonth = may,\n\tyear = {2023},\n\tnote = {Number: 5\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {DDM, HCS, gastric cancer},\n\tpages = {1077},\n}\n\n

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\n \n\n \n \n \n \n \n \n Post-mortem genetic testing in sudden cardiac death and genetic screening of relatives at risk: lessons learned from a Czech pilot multidisciplinary study.\n \n \n \n \n\n\n \n Votýpka, P.; Krebsová, A.; Norambuena-Poustková, P.; Peldová, P.; Pohlová Kučerová, Š.; Kulvajtová, M.; Dohnalová, P.; Bílek, M.; Stufka, V.; Rücklová, K.; Grossová, I.; Wünschová, H.; Tavačová, T.; Hašková, J.; Segeťová, M.; Štoček, J.; Gřegořová, A.; Zoubková, V.; Petřková, J.; Dobiáš, M.; Makuša, M.; Blanková, A.; Vajtr, D.; Řehulka, H.; Šubrt, I.; Pilin, A.; Tomášek, P.; Janoušek, J.; Kautzner, J.; and Macek, M.\n\n\n \n\n\n\n International Journal of Legal Medicine. May 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Post-mortem$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{votypka_post-mortem_2023,\n\ttitle = {Post-mortem genetic testing in sudden cardiac death and genetic screening of relatives at risk: lessons learned from a {Czech} pilot multidisciplinary study},\n\tissn = {1437-1596},\n\tshorttitle = {Post-mortem genetic testing in sudden cardiac death and genetic screening of relatives at risk},\n\turl = {https://doi.org/10.1007/s00414-023-03007-z},\n\tdoi = {10.1007/s00414-023-03007-z},\n\tabstract = {Sudden cardiac death (SCD) might have an inherited cardiac condition background. Genetic testing supports post-mortem diagnosis and screening of relatives at risk. Our aim is to determine the feasibility of a Czech national collaboration group and to establish the clinical importance of molecular autopsy and family screening. From 2016 to 2021, we have evaluated 100 unrelated SCD cases (71.0\\% males, age: 33.3 (12.8) years). Genetic testing was performed by next-generation sequencing utilizing a panel of 100 genes related to inherited cardiac/aortic conditions and/or whole exome sequencing. According to autopsy, cases were divided into cardiomyopathies, sudden arrhythmic death syndrome, sudden unexplained death syndrome, and sudden aortic death. We identified pathogenic/likely pathogenic variants following ACMG/AMP recommendations in 22/100 (22.0\\%) of cases. Since poor DNA quality, we have performed indirect DNA testing in affected relatives or in healthy parents reaching a diagnostic genetic yield of 11/24 (45.8\\%) and 1/10 (10.0\\%), respectively. Cardiological and genetic screening disclose 83/301 (27.6\\%) relatives at risk of SCD. Genetic testing in affected relatives as starting material leads to a high diagnostic yield offering a valuable alternative when suitable material is not available. This is the first multidisciplinary/multicenter molecular autopsy study in the Czech Republic which supports the establishment of this type of diagnostic tests. A central coordinator and proper communication among centers are crucial for the success of a collaboration at a national level.},\n\tlanguage = {en},\n\turldate = {2023-06-16},\n\tjournal = {International Journal of Legal Medicine},\n\tauthor = {Votýpka, Pavel and Krebsová, Alice and Norambuena-Poustková, Patricia and Peldová, Petra and Pohlová Kučerová, Štěpánka and Kulvajtová, Markéta and Dohnalová, Petra and Bílek, Matěj and Stufka, Veronika and Rücklová, Kristina and Grossová, Iva and Wünschová, Hanka and Tavačová, Terezia and Hašková, Jana and Segeťová, Markéta and Štoček, Jakub and Gřegořová, Andrea and Zoubková, Veronika and Petřková, Jana and Dobiáš, Martin and Makuša, Michal and Blanková, Alžběta and Vajtr, David and Řehulka, Hynek and Šubrt, Ivan and Pilin, Alexander and Tomášek, Petr and Janoušek, Jan and Kautzner, Josef and Macek, Milan},\n\tmonth = may,\n\tyear = {2023},\n\tkeywords = {Alamut, Custom Panel, Custom panel of 100 genes, DDM, Forensic genetics, Inherited cardiovascular diseases, Molecular autopsy, WES},\n}\n\n

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\n \n\n \n \n \n \n \n \n Early diagnosis of congenital muscular pathologies using next-generation sequencing: experiences from a tertiary center in Morocco.\n \n \n \n \n\n\n \n El Kadiri, Y.; Ratbi, I.; Ouhenach, M.; Chafai Elalaoui, S.; Cherkaoui Jaouad, I.; Zrhidri, A.; Sahli, M.; Birouk, N.; Sefiani, A.; and Lyahyai, J.\n\n\n \n\n\n\n Egyptian Journal of Medical Human Genetics, 24(1): 36. May 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Early$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{el_kadiri_early_2023,\n\ttitle = {Early diagnosis of congenital muscular pathologies using next-generation sequencing: experiences from a tertiary center in {Morocco}},\n\tvolume = {24},\n\tissn = {2090-2441},\n\tshorttitle = {Early diagnosis of congenital muscular pathologies using next-generation sequencing},\n\turl = {https://doi.org/10.1186/s43042-023-00416-y},\n\tdoi = {10.1186/s43042-023-00416-y},\n\tabstract = {Congenital muscular dystrophies (CMD) and congenital myopathies (CM) are clinically and genetically heterogeneous groups of neuromuscular disorders resulting in prenatal or early-onset hypotonia, muscle weakness, myogenic pattern, and dystrophic or myopathic features on muscle biopsy. In this study, we provide a genetic and molecular characterization of CMD and CM in Moroccan patients.},\n\tnumber = {1},\n\turldate = {2023-06-16},\n\tjournal = {Egyptian Journal of Medical Human Genetics},\n\tauthor = {El Kadiri, Youssef and Ratbi, Ilham and Ouhenach, Mouna and Chafai Elalaoui, Siham and Cherkaoui Jaouad, Imane and Zrhidri, Abdelali and Sahli, Maryem and Birouk, Nazha and Sefiani, Abdelaziz and Lyahyai, Jaber},\n\tmonth = may,\n\tyear = {2023},\n\tkeywords = {CES v2, Congenital muscular dystrophy, Congenital myopathy, DDM, Neonatal hypotonia},\n\tpages = {36},\n}\n\n

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\n \n\n \n \n \n \n \n \n A truncating variant altering the extreme C-terminal region of desmoplakin (DSP) suggests the crucial functional role of the region: a case report study \\textbar BMC Medical Genomics \\textbar Full Text.\n \n \n \n \n\n\n \n \n\n\n \n\n\n\n May 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@misc{noauthor_truncating_2023,\n\ttitle = {A truncating variant altering the extreme {C}-terminal region of desmoplakin ({DSP}) suggests the crucial functional role of the region: a case report study {\\textbar} {BMC} {Medical} {Genomics} {\\textbar} {Full} {Text}},\n\turl = {https://bmcmedgenomics.biomedcentral.com/articles/10.1186/s12920-023-01527-6},\n\turldate = {2023-06-16},\n\tmonth = may,\n\tyear = {2023},\n\tkeywords = {DDM, SG pipeline},\n}\n\n

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\n \n\n \n \n \n \n \n \n Early-onset gout and rare deficient variants of the lactate dehydrogenase D gene.\n \n \n \n \n\n\n \n Bardin, T.; Ducrot, Y.; Nguyen, Q.; Letavernier, E.; Zaworski, J.; Ea, H.; Touzain, F.; Do, M. D.; Colot, J.; Barguil, Y.; Biron, A.; Resche-Rigon, M.; Richette, P.; and Collet, C.\n\n\n \n\n\n\n Rheumatology,kead118. April 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Early-onset$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{bardin_early-onset_2023,\n\ttitle = {Early-onset gout and rare deficient variants of the lactate dehydrogenase {D} gene},\n\tissn = {1462-0324},\n\turl = {https://doi.org/10.1093/rheumatology/kead118},\n\tdoi = {10.1093/rheumatology/kead118},\n\tabstract = {To investigate whether the lactate dehydrogenase D (LDHD) gene deficiency causes juvenile-onset gout.We used whole-exome sequencing for two families and a targeted gene-sequencing panel for an isolated patient. d-lactate dosages were analysed using ELISA.We demonstrated linkage of juvenile-onset gout to homozygous carriage of three rare distinct LDHD variants in three different ethnicities. In a Melanesian family, the variant was (NM\\_153486.3: c.206C\\&gt;T; rs1035398551) and, as compared with non-homozygotes, homozygotes had higher hyperuricaemia (P = 0.02), lower fractional clearance of urate (P = 0.002), and higher levels of d-lactate in blood (P = 0.04) and urine (P = 0.06). In a second, Vietnamese, family, very severe juvenile-onset gout was linked to homozygote carriage of an undescribed LDHD variant (NM\\_153486.3: c.1363dupG) leading to a frameshift followed by a stop codon, p.(AlaGly432fsTer58). Finally, a Moroccan man, with early-onset and high d-lactaturia, whose family was unavailable for testing, was homozygous for another rare LDHD variant [NM\\_153486.3: c.752C\\&gt;T, p.(Thr251Met)].Rare, damaging LDHD variants can cause autosomal recessive early-onset gout, the diagnosis of which can be suspected by measuring high d-lactate levels in the blood and/or urine.},\n\turldate = {2023-06-16},\n\tjournal = {Rheumatology},\n\tauthor = {Bardin, Thomas and Ducrot, Yves-Marie and Nguyen, Quang and Letavernier, Emmanuel and Zaworski, Jeremy and Ea, Hang-Korng and Touzain, Fréderic and Do, Minh Duc and Colot, Julien and Barguil, Yann and Biron, Antoine and Resche-Rigon, Matthieu and Richette, Pascal and Collet, Corinne},\n\tmonth = apr,\n\tyear = {2023},\n\tkeywords = {Alamut},\n\tpages = {kead118},\n}\n\n

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\n \n\n \n \n \n \n \n \n A homozygous loss of function variant in POPDC3: From invalidating exercise intolerance to a limb-girdle muscular dystrophy phenotype.\n \n \n \n \n\n\n \n De Ridder, W.; de Vries, G.; Van Schil, K.; Deconinck, T.; Mouly, V.; Straub, V.; and Baets, J.\n\n\n \n\n\n\n Neuromuscular Disorders, 33(5): 432–439. April 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{de_ridder_homozygous_2023,\n\ttitle = {A homozygous loss of function variant in {POPDC3}: {From} invalidating exercise intolerance to a limb-girdle muscular dystrophy phenotype},\n\tvolume = {33},\n\tissn = {0960-8966},\n\tshorttitle = {A homozygous loss of function variant in {POPDC3}},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0960896623001037},\n\tdoi = {10.1016/j.nmd.2023.04.003},\n\tabstract = {Recessive pathogenic variants in POPDC3 have recently been associated with the rare limb-girdle muscular dystrophy (LGMD) subtype LGMDR26. We studied three siblings and a distantly related individual with a skeletal muscle disorder, harboring the c.486–6T{\\textgreater}A splice site variant in POPDC3 in homozygosity. Immunohistochemistry, western blot, and mRNA experiments on patients’ skeletal muscle tissue as well as on patients’ myoblasts were performed to study the pathogenicity of the predicted loss of function mechanism of the variant. Patients mainly presented with invalidating myalgia and exercise intolerance and limited to no segmentary muscle weakness. CK levels were markedly elevated in all patients. A loss of function mechanism at the RNA level was shown (r.485\\_486insauag, p.Ile163*). Muscle biopsies performed in three out of four patients showed non-specific myopathic features with a marked type 2 fiber predominance and the presence of a large number of severely atrophic fibers with pyknotic nuclear clumps. We show that skeletal muscle symptoms in LGMDR26 may range from an overt late juvenile to young adult-onset limb-girdle muscular dystrophy phenotype to severe exercise intolerance and myalgia, with consistently highly elevated CK levels. We further prove a clear LOF mechanism of POPDC3 in this rare disorder.},\n\tlanguage = {en},\n\tnumber = {5},\n\turldate = {2023-06-16},\n\tjournal = {Neuromuscular Disorders},\n\tauthor = {De Ridder, Willem and de Vries, Geert and Van Schil, Kristof and Deconinck, Tine and Mouly, Vincent and Straub, Volker and Baets, Jonathan},\n\tmonth = apr,\n\tyear = {2023},\n\tkeywords = {Alamut Visual Plus v.1.4, HyperCKemia, LGMDR26, POPDC3},\n\tpages = {432--439},\n}\n\n

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\n \n\n \n \n \n \n \n \n Disruptive and Truncating TP53 Mutations Are Associated with African-Ancestry and Worse Prognosis in Brazilian Patients with Lung Adenocarcinoma.\n \n \n \n \n\n\n \n Cavagna, R. d. O.; Pinto, I. A.; Escremim de Paula, F.; Berardinelli, G. N.; Sant'Anna, D.; Santana, I.; Da Silva, V. D.; da Silva, E. C. A.; Miziara, J. E.; Mourao, J.; Antoniazzi, A.; Jacinto, A.; De Marchi, P.; Molina, M. A.; Ferro Leal, L.; and Reis, R. M.\n\n\n \n\n\n\n Pathobiology,1. April 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Disruptive$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{cavagna_disruptive_2023,\n\ttitle = {Disruptive and {Truncating} {TP53} {Mutations} {Are} {Associated} with {African}-{Ancestry} and {Worse} {Prognosis} in {Brazilian} {Patients} with {Lung} {Adenocarcinoma}},\n\tissn = {1015-2008},\n\turl = {https://doi.org/10.1159/000530587},\n\tdoi = {10.1159/000530587},\n\tabstract = {Introduction:TP53 is the most frequently mutated gene in lung tumors, but its prognostic role in admixed populations, such as Brazilians, remains unclear. In this study, we aimed to evaluate the frequency and clinicopathological impact of TP53 mutations in non-small cell lung cancer (NSCLC) patients in Brazil. Methods: We analyzed 446 NSCLC patients from Barretos Cancer Hospital. TP53 mutational status was evaluated through targeted next-generation sequencing (NGS) and the variants were biologically classified as disruptive/nondisruptive and as truncating/nontruncating. We also assessed genetic ancestry using 46 ancestry-informative markers. Analysis of lung adenocarcinomas from the cBioportal dataset was performed. We further examined associations of TP53 mutations with patients’ clinicopathological features. Results:TP53 mutations were detected in 64.3\\% (n = 287/446) of NSCLC cases, with a prevalence of 60.4\\% (n = 221/366) in lung adenocarcinomas. TP53 mutations were associated with brain metastasis at diagnosis, tobacco consumption, and higher African ancestry. Disruptive and truncating mutations were associated with a younger age at diagnosis. Additionally, cBioportal dataset revealed that TP53 mutations were associated with younger age and Black skin color. Patients harboring disruptive/truncating TP53 mutations had worse overall survival than nondisruptive/nontruncating and wild-type patients. Conclusion:TP53 mutations are common in Brazilian lung adenocarcinomas, and their biological characterization as disruptive and truncating mutations is associated with African ancestry and shorter overall survival.},\n\turldate = {2023-06-16},\n\tjournal = {Pathobiology},\n\tauthor = {Cavagna, Rodrigo de Oliveira and Pinto, Icaro Alves and Escremim de Paula, Flávia and Berardinelli, Gustavo Noriz and Sant'Anna, Débora and Santana, Iara and Da Silva, Vinicius Duval and da Silva, Eduardo Caetano Albino and Miziara, José Elias and Mourao, Josiane and Antoniazzi, Augusto and Jacinto, Alexandre and De Marchi, Pedro and Molina, Miguel Angel and Ferro Leal, Leticia and Reis, Rui Manuel},\n\tmonth = apr,\n\tyear = {2023},\n\tkeywords = {DDM, DDM v4.2},\n\tpages = {1},\n}\n\n

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\n \n\n \n \n \n \n \n \n BRCA1 and BRCA2 germline mutation analysis from a cohort of 1267 patients at high risk for breast cancer in Brazil.\n \n \n \n \n\n\n \n Mazzonetto, P.; Milanezi, F.; D’Andrea, M.; Martins, S.; Monfredini, P. M.; dos Santos Silva, J.; Perrone, E.; Villela, D.; Schnabel, B.; Nakano, V.; Palmero, E. I.; Braggio, E.; Cavalcanti, T. L.; Guida, G.; Migliavacca, M. P.; Scapulatempo-Neto, C.; and Zalcberg, I.\n\n\n \n\n\n\n Breast Cancer Research and Treatment, 199(1): 127–136. March 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"BRCA1$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{mazzonetto_brca1_2023,\n\ttitle = {{BRCA1} and {BRCA2} germline mutation analysis from a cohort of 1267 patients at high risk for breast cancer in {Brazil}},\n\tvolume = {199},\n\tissn = {1573-7217},\n\turl = {https://doi.org/10.1007/s10549-023-06892-5},\n\tdoi = {10.1007/s10549-023-06892-5},\n\tabstract = {We determined the frequency and mutational spectrum of BRCA1 and BRCA2 in a series of patients at high risk for developing breast cancer from Brazil. A total of 1267 patients were referred for BRCA genetic testing, and no obligation of fulfilling criteria of mutation probability methods for molecular screening was applied. Germline deleterious mutations in BRCA1/2 (i.e., pathogenic/likely pathogenic variants) were identified in 156 out of 1267 patients (12\\%). We confirm recurrent mutations in BRCA1/2, but we also report three novel mutations in BRCA2, not previously reported in any public databases or other studies. Variants of unknown significance (VUS) represent only 2\\% in this dataset and most of them were detected in BRCA2. The overall mutation prevalence in BRCA1/2 was higher in patients diagnosed with cancer at age {\\textgreater} 35 years old, and with family history of cancer. The present data expand our knowledge of BRCA1/2 germline mutational spectrum, and it is a valuable clinical resource for genetic counseling and cancer management programs in the country.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2023-06-16},\n\tjournal = {Breast Cancer Research and Treatment},\n\tauthor = {Mazzonetto, Patricia and Milanezi, Fernanda and D’Andrea, Mariana and Martins, Silvia and Monfredini, Priscilla M. and dos Santos Silva, Juliana and Perrone, Eduardo and Villela, Darine and Schnabel, Beatriz and Nakano, Viviane and Palmero, Edenir Inez and Braggio, Esteban and Cavalcanti, Thereza L. and Guida, Gustavo and Migliavacca, Michele P. and Scapulatempo-Neto, Cristovam and Zalcberg, Ilana},\n\tmonth = mar,\n\tyear = {2023},\n\tkeywords = {Alamut Visual Plus, BRCA1, BRCA2, DDM, HCS, Hereditary breast and ovarian cancer},\n\tpages = {127--136},\n}\n\n

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\n \n\n \n \n \n \n \n \n Integrated genetic profiling of archival pediatric high-grade glial tumors and reassessment with 2021 WHO classification of paediatric CNS tumours.\n \n \n \n \n\n\n \n Cooley, L. D.; Lansdon, L. A.; Laurence, K.; Herriges, J. C.; Zhang, L.; Repnikova, E. A.; Joyce, J.; Thakor, P.; Warren, L.; Smith, S. C.; Yoo, B.; Gener, M.; Ginn, K. F.; and Farooqi, M. S.\n\n\n \n\n\n\n Cancer Genetics, 274: 10–20. March 2023.\n Publisher: Elsevier\n\n\n\n
\n\n\n\n \n \n $\"Integrated$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{cooley_integrated_2023,\n\ttitle = {Integrated genetic profiling of archival pediatric high-grade glial tumors and reassessment with 2021 {WHO} classification of paediatric {CNS} tumours},\n\tvolume = {274},\n\tissn = {2210-7762},\n\turl = {https://www.cancergeneticsjournal.org/article/S2210-7762(23)00008-X/fulltext},\n\tdoi = {10.1016/j.cancergen.2023.02.004},\n\tlanguage = {English},\n\turldate = {2023-06-16},\n\tjournal = {Cancer Genetics},\n\tauthor = {Cooley, Linda D. and Lansdon, Lisa A. and Laurence, Kris and Herriges, John C. and Zhang, Lei and Repnikova, Elena A. and Joyce, Julie and Thakor, Preeti and Warren, Lisa and Smith, Scott C. and Yoo, Byunggil and Gener, Melissa and Ginn, Kevin F. and Farooqi, Midhat S.},\n\tmonth = mar,\n\tyear = {2023},\n\tpmid = {36917897},\n\tnote = {Publisher: Elsevier},\n\tkeywords = {Alamut, High-grade glioma, OncoScan microarray, Sequencing},\n\tpages = {10--20},\n}\n\n

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\n \n\n \n \n \n \n \n \n Comparative Genomic Profiling of Second Breast Cancers following First Ipsilateral Hormone Receptor–Positive Breast Cancers.\n \n \n \n \n\n\n \n Rassy, E.; Garberis, I.; Tran-Dien, A.; Job, B.; Chung-Scott, V.; Bouakka, I.; Bassil, J.; Ferkh, R.; Lacroix-Triki, M.; Zanconati, F.; Giudici, F.; Generali, D.; Rouleau, E.; Lacroix, L.; Andre, F.; and Pistilli, B.\n\n\n \n\n\n\n Clinical Cancer Research, 29(9): 1822–1831. February 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Comparative$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{rassy_comparative_2023,\n\ttitle = {Comparative {Genomic} {Profiling} of {Second} {Breast} {Cancers} following {First} {Ipsilateral} {Hormone} {Receptor}–{Positive} {Breast} {Cancers}},\n\tvolume = {29},\n\tissn = {1078-0432},\n\turl = {https://doi.org/10.1158/1078-0432.CCR-22-2883},\n\tdoi = {10.1158/1078-0432.CCR-22-2883},\n\tabstract = {We compared the mutational profile of second breast cancers (SBC) following first ipislateral hormone receptor–positive breast cancers of patient-matched tumors to distinguish new primaries from true recurrences.Targeted next-generation sequencing using the Oncomine Tumor Mutation Load Assay. Variants were filtered according to their allele frequency ≥ 5\\%, read count ≥ 5X, and genomic effect and annotation. Whole genome comparative genomic hybridization array (CGH) was also performed to evaluate clonality.Among the 131 eligible patients, 96 paired first breast cancer (FBC) and SBC were successfully sequenced and analyzed. Unshared variants specific to the FBC and SBC were identified in 71.9\\% and 61.5\\%, respectively. Paired samples exhibited similar frequency of gene variants, median number of variants per sample, and variant allele frequency of the reported variants except for GATA3. Among the 30 most frequent gene alterations, ARIDIA, NSD2, and SETD2 had statistically significant discordance rates in paired samples. Seventeen paired samples (17.7\\%) exhibited common variants and were considered true recurrences; these patients had a trend for less favorable survival outcomes. Among the 8 patients with available tissue for CGH analysis and considered new primaries by comparison of the mutation profiles, 4 patients had clonally related tumors.Patient-matched FBC and SBC analysis revealed that only a minority of patients exhibited common gene variants between the first and second tumor. Further analysis using larger cohorts, preferably using single-cell analyses to account for clonality, might better select patients with true recurrences and thereby better inform the decision-making process.},\n\tnumber = {9},\n\turldate = {2023-06-16},\n\tjournal = {Clinical Cancer Research},\n\tauthor = {Rassy, Elie and Garberis, Ingrid and Tran-Dien, Alicia and Job, Bastien and Chung-Scott, Véronique and Bouakka, Ibrahim and Bassil, Josiane and Ferkh, Rachel and Lacroix-Triki, Magali and Zanconati, Fabrizio and Giudici, Fabiola and Generali, Daniele and Rouleau, Etienne and Lacroix, Ludovic and Andre, Fabrice and Pistilli, Barbara},\n\tmonth = feb,\n\tyear = {2023},\n\tkeywords = {Alamut Visual v2.15},\n\tpages = {1822--1831},\n}\n\n

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\n \n\n \n \n \n \n \n \n Dravet syndrome and hemorrhagic shock and encephalopathy syndrome associated with an intronic deletion of SCN1A.\n \n \n \n \n\n\n \n Hanafusa, H.; Yamaguchi, H.; Kondo, H.; Nagasaka, M.; Juan Ye, M.; Oikawa, S.; Tokumoto, S.; Tomioka, K.; Nishiyama, M.; Morisada, N.; Matsuo, M.; Nozu, K.; and Nagase, H.\n\n\n \n\n\n\n Brain and Development, 45(6): 317–323. February 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Dravet$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{hanafusa_dravet_2023,\n\ttitle = {Dravet syndrome and hemorrhagic shock and encephalopathy syndrome associated with an intronic deletion of {SCN1A}},\n\tvolume = {45},\n\tissn = {0387-7604},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0387760423000219},\n\tdoi = {10.1016/j.braindev.2023.01.008},\n\tabstract = {Objective\nHemorrhagic shock and encephalopathy syndrome (HSES) is a serious condition that requires intensive care and is associated with a high mortality rate. However, its pathogenesis remains unclear. In the present study, a genetic analysis was performed to determine the genetic background of patients with clinically suspected Dravet syndrome (DS) who developed HSES.\nMethods\nWhole exome sequencing was performed, followed by minigene analysis of the intron variant detected by whole exome sequencing to confirm its effect on splicing.\nResults\nWhole exome sequencing revealed a novel 21-bp deletion in intron 3 of SCN1A NM\\_001165963.4 (NC\\_000002.11:g.166073675\\_166073695del). This deletion was not found in the patient’s parents and was proven to be de novo. Minigene analysis revealed an aberrant mRNA lacking 40 and 106 bp from the 5′ end of exon 4 of SCN1A. Therefore, we diagnosed this case as DS due to the deletion in intron 3 of SCN1A.\nConclusions\nWe report a case of DS with HSES caused by a 21-bp deletion in the intron of SCN1A that was confirmed by minigene analysis. The present case met Levin's criteria for HSES and the splicing analysis of SCN1A is an important finding. This study has important implications for understanding HSES pathogenesis.},\n\tlanguage = {en},\n\tnumber = {6},\n\turldate = {2023-06-16},\n\tjournal = {Brain and Development},\n\tauthor = {Hanafusa, Hiroaki and Yamaguchi, Hiroshi and Kondo, Hidehito and Nagasaka, Miwako and Juan Ye, Ming and Oikawa, Shizuka and Tokumoto, Shoichi and Tomioka, Kazumi and Nishiyama, Masahiro and Morisada, Naoya and Matsuo, Masafumi and Nozu, Kandai and Nagase, Hiroaki},\n\tmonth = feb,\n\tyear = {2023},\n\tkeywords = {Alamut Visual Plus, Alamut Visual plus v.1.5.1, Dravet syndrome, Epilepsy, Whole exome sequencing},\n\tpages = {317--323},\n}\n\n

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\n \n\n \n \n \n \n \n \n Clinical interest of molecular study in cases of isolated midline craniosynostosis.\n \n \n \n \n\n\n \n Di Rocco, F.; Rossi, M.; Verlut, I.; Szathmari, A.; Beuriat, P. A.; Chatron, N.; Chauvel-Picard, J.; Mottolese, C.; Monin, P.; Vinchon, M.; Guernouche, S.; and Collet, C.\n\n\n \n\n\n\n European Journal of Human Genetics, 31(6): 621–628. February 2023.\n Number: 6 Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"Clinical$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{di_rocco_clinical_2023,\n\ttitle = {Clinical interest of molecular study in cases of isolated midline craniosynostosis},\n\tvolume = {31},\n\tcopyright = {2023 The Author(s), under exclusive licence to European Society of Human Genetics},\n\tissn = {1476-5438},\n\turl = {https://www.nature.com/articles/s41431-023-01295-y},\n\tdoi = {10.1038/s41431-023-01295-y},\n\tabstract = {In some cases of infants with apparently isolated single-suture synostosis, an underlying variant can be found. We aimed to determine the molecular substratum in isolated sagittal and metopic craniosynostosis. To this end, we included all infants who presented isolated midline synostosis (sagittal or metopic) and had undergone surgery at the craniosynostosis national reference center of Lyon University Hospital. All infants were examined by a multidisciplinary team including neurosurgeons, clinical geneticists and neuropsychologist. Among 101 infants tested, 13 carried a total of 13 variants; that is, 12.9\\% of the infants carried a variant in genes known to be involved in craniosynostosis. Seven infants carried SMAD6 variants, 2 in FGFR2, 1 in TWIST1, one in FREM1, one in ALX4 and one in TCF12. All variants were detected at the heterozygous level in genes associated with autosomal dominant craniosynostosis. Also, neurodevelopmental testing showed especially delayed acquisition of language in children with than without variants in SMAD6. In conclusion, a high percentage of young children with isolated midline craniosynostosis, especially in isolated trigonocephaly, carried SMAD6 variants. The interpretation of the pathogenicity of the genes must take into account incomplete penetrance, usually observed in craniosynostosis. Our results highlight the interest of molecular analysis in the context of isolated sagittal and/or metopic craniosynostosis to enhance an understanding of the pathophysiology of midline craniosynostosis.},\n\tlanguage = {en},\n\tnumber = {6},\n\turldate = {2023-06-16},\n\tjournal = {European Journal of Human Genetics},\n\tauthor = {Di Rocco, Federico and Rossi, Massimiliano and Verlut, Isabelle and Szathmari, Alexandru and Beuriat, Pierre Aurélien and Chatron, Nicolas and Chauvel-Picard, Julie and Mottolese, Carmine and Monin, Pauline and Vinchon, Matthieu and Guernouche, Sofia and Collet, Corinne},\n\tmonth = feb,\n\tyear = {2023},\n\tnote = {Number: 6\nPublisher: Nature Publishing Group},\n\tkeywords = {Alamut},\n\tpages = {621--628},\n}\n\n

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\n \n\n \n \n \n \n \n \n Heterozygous pathogenic variation in GCH1 associated with treatable severe spastic tetraplegia.\n \n \n \n \n\n\n \n Ravel, J.; Michaud, M.; Frismand, S.; Puisieux, S.; Banneau, G.; Benoist, J.; Lambert, L.; Bonnet, C.; and Renaud, M.\n\n\n \n\n\n\n Parkinsonism & Related Disorders, 109. February 2023.\n Publisher: Elsevier\n\n\n\n
\n\n\n\n \n \n $\"Heterozygous$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{ravel_heterozygous_2023,\n\ttitle = {Heterozygous pathogenic variation in {GCH1} associated with treatable severe spastic tetraplegia},\n\tvolume = {109},\n\tissn = {1353-8020, 1873-5126},\n\turl = {https://www.prd-journal.com/article/S1353-8020(23)00033-0/fulltext},\n\tdoi = {10.1016/j.parkreldis.2023.105310},\n\tlanguage = {English},\n\turldate = {2023-06-16},\n\tjournal = {Parkinsonism \\& Related Disorders},\n\tauthor = {Ravel, Jean-Marie and Michaud, Maud and Frismand, Solène and Puisieux, Salomé and Banneau, Guillaume and Benoist, Jean-François and Lambert, Laëtitia and Bonnet, Céline and Renaud, Mathilde},\n\tmonth = feb,\n\tyear = {2023},\n\tpmid = {36803911},\n\tnote = {Publisher: Elsevier},\n\tkeywords = {CES, CES v2, clinical exome sequencing},\n}\n\n

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\n \n\n \n \n \n \n \n \n Analysis of 200 unrelated individuals with a constitutional NF1 deep intronic pathogenic variant reveals that variants flanking the alternatively spliced NF1 exon 31 [23a] cause a classical neurofibromatosis type 1 phenotype while altering predominantly NF1 isoform type II \\textbar SpringerLink.\n \n \n \n \n\n\n \n \n\n\n \n\n\n\n April 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Analysis$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@misc{noauthor_analysis_2023,\n\ttitle = {Analysis of 200 unrelated individuals with a constitutional {NF1} deep intronic pathogenic variant reveals that variants flanking the alternatively spliced {NF1} exon 31 [23a] cause a classical neurofibromatosis type 1 phenotype while altering predominantly {NF1} isoform type {II} {\\textbar} {SpringerLink}},\n\turl = {https://link.springer.com/article/10.1007/s00439-023-02555-z},\n\turldate = {2023-05-10},\n\tmonth = apr,\n\tyear = {2023},\n\tkeywords = {Alamut, Alamut v.1.6.1},\n}\n\n

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\n \n\n \n \n \n \n \n \n Functional analyses of rare germline BRCA1 variants by transcriptional activation and homologous recombination repair assays.\n \n \n \n \n\n\n \n Bassi, N.; Hovland, H. N.; Rasheed, K.; Jarhelle, E.; Pedersen, N.; Mchaina, E. K.; Bakkan, S. M. E.; Iversen, N.; Høberg-Vetti, H.; Haukanes, B. I.; Knappskog, P. M.; Aukrust, I.; Ognedal, E.; and Van Ghelue, M.\n\n\n \n\n\n\n BMC Cancer, 23(1): 368. April 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Functional$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{bassi_functional_2023,\n\ttitle = {Functional analyses of rare germline {BRCA1} variants by transcriptional activation and homologous recombination repair assays},\n\tvolume = {23},\n\tissn = {1471-2407},\n\turl = {https://doi.org/10.1186/s12885-023-10790-w},\n\tdoi = {10.1186/s12885-023-10790-w},\n\tabstract = {Damaging alterations in the BRCA1 gene have been extensively described as one of the main causes of hereditary breast and ovarian cancer (HBOC).BRCA1 alterations can lead to impaired homologous recombination repair (HRR) of double-stranded DNA breaks, a process which involves the RING, BRCT and coiled-coil domains of the BRCA1 protein. In addition, the BRCA1 protein is involved in transcriptional activation (TA) of several genes through its C-terminal BRCT domain.},\n\tnumber = {1},\n\turldate = {2023-05-10},\n\tjournal = {BMC Cancer},\n\tauthor = {Bassi, Nicola and Hovland, Henrikke Nilsen and Rasheed, Kashif and Jarhelle, Elisabeth and Pedersen, Nikara and Mchaina, Eunice Kabanyana and Bakkan, Sara Marie Engelsvold and Iversen, Nina and Høberg-Vetti, Hildegunn and Haukanes, Bjørn Ivar and Knappskog, Per Morten and Aukrust, Ingvild and Ognedal, Elisabet and Van Ghelue, Marijke},\n\tmonth = apr,\n\tyear = {2023},\n\tkeywords = {Alamut, Alamut Software v.2.15, Alamut v.2.15, BRCA1, Hereditary breast and ovarian cancer},\n\tpages = {368},\n}\n\n

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\n \n\n \n \n \n \n \n \n In-house homologous recombination deficiency testing in ovarian cancer: a multi-institutional Italian pilot study.\n \n \n \n \n\n\n \n Pepe, F.; Guerini-Rocco, E.; Fassan, M.; Fusco, N.; Vacirca, D.; Ranghiero, A.; Venetis, K.; Rappa, A.; Taormina, S. V.; Russo, G.; Rebellato, E.; Munari, G.; Moreno-Manuel, A.; Angelis, C. D.; Zamagni, C.; Valabrega, G.; Malapelle, U.; Troncone, G.; Barberis, M.; and Iaccarino, A.\n\n\n \n\n\n\n Journal of Clinical Pathology. April 2023.\n Publisher: BMJ Publishing Group Section: Original research\n\n\n\n
\n\n\n\n \n \n $\"In-house$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{pepe_-house_2023,\n\ttitle = {In-house homologous recombination deficiency testing in ovarian cancer: a multi-institutional {Italian} pilot study},\n\tcopyright = {© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.},\n\tissn = {0021-9746, 1472-4146},\n\tshorttitle = {In-house homologous recombination deficiency testing in ovarian cancer},\n\turl = {https://jcp.bmj.com/content/early/2023/04/25/jcp-2023-208852},\n\tdoi = {10.1136/jcp-2023-208852},\n\tabstract = {Aims Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPIs) represent a standard of care for the clinical management of high-grade serous ovarian cancer (HGSOC). The recognition of homologous recombination deficiency (HRD) has emerged as a predictive biomarker of response for first-line PARPIs treatment in patients with HGOSC. On the other hand, this test is extremely complex and therefore it is often externalised. Regrettably, the reliability of outsourced HRD testing can be troubled by inconclusive results and high rejection rates. In this methodological study, we assessed the technical feasibility, interassay and interlaboratory reproducibility of in-house HRD testing using three different commercially available next-generation sequencing assays.\nMethods A total of n=20 epithelial ovarian cancer samples previously analysed with MyChoice CDx were subjected to HRD retesting using three different platforms in three different major pathology laboratories, that is, SOPHiA DDM HRD Solution, HRD focus and Oncomine homologous recombination repair pathway predesigned panel. Concordance was calculated by Cohen’s (dual) and Fleiss (triple) κ coefficients.\nResults In-house BRCA1/2 molecular testing yielded a concordance rate {\\textgreater}90.0\\% among all participating centres. HRD scores were successfully calculated by each institution with a concordance rate of 76.5\\%. Concerning the external gold standard test, the overall percentage of agreement ranged from 80.0\\% to 90.0\\% with a positive percentage agreement ranging from 75.0\\% to 80.0\\% and a negative percentage agreement ranging from 80.0\\% to 100\\%.\nConclusions In-house testing for HRD can be reliably performed with commercially available next-generation sequencing assays.},\n\tlanguage = {en},\n\turldate = {2023-05-10},\n\tjournal = {Journal of Clinical Pathology},\n\tauthor = {Pepe, Francesco and Guerini-Rocco, Elena and Fassan, Matteo and Fusco, Nicola and Vacirca, Davide and Ranghiero, Alberto and Venetis, Konstantinos and Rappa, Alessandra and Taormina, Sergio Vincenzo and Russo, Gianluca and Rebellato, Elena and Munari, Giada and Moreno-Manuel, Andrea and Angelis, Carmine De and Zamagni, Claudio and Valabrega, Giorgio and Malapelle, Umberto and Troncone, Giancarlo and Barberis, Massimo and Iaccarino, Antonino},\n\tmonth = apr,\n\tyear = {2023},\n\tpmid = {37072171},\n\tnote = {Publisher: BMJ Publishing Group\nSection: Original research},\n\tkeywords = {HRD, ovarian neoplasms, pathology, molecular},\n}\n\n

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\n \n\n \n \n \n \n \n \n Molecular diagnostics.\n \n \n \n \n\n\n \n \n\n\n \n\n\n\n Clinical Chemistry and Laboratory Medicine (CCLM), 61(s1): s1748–s1851. April 2023.\n Publisher: De Gruyter\n\n\n\n
\n\n\n\n \n \n $\"Molecular$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{noauthor_molecular_2023,\n\ttitle = {Molecular diagnostics},\n\tvolume = {61},\n\tissn = {1437-4331},\n\turl = {https://www.degruyter.com/document/doi/10.1515/cclm-2023-7057/html?lang=en},\n\tdoi = {10.1515/cclm-2023-7057},\n\tabstract = {Article Molecular diagnostics was published on May 1, 2023 in the journal Clinical Chemistry and Laboratory Medicine (CCLM) (volume 61, issue s1).},\n\tlanguage = {en},\n\tnumber = {s1},\n\turldate = {2023-05-10},\n\tjournal = {Clinical Chemistry and Laboratory Medicine (CCLM)},\n\tmonth = apr,\n\tyear = {2023},\n\tnote = {Publisher: De Gruyter},\n\tkeywords = {CES, Custom Panel, Customer Fever \\& Autoinflammatory Disease, DDM, DDM v.5.10.15, DDM v.5.8.0.3, HRD},\n\tpages = {s1748--s1851},\n}\n\n

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\n \n\n \n \n \n \n \n \n Precision Medicine.\n \n \n \n \n\n\n \n \n\n\n \n\n\n\n Clinical Chemistry and Laboratory Medicine (CCLM), 61(s1): s1925–s1960. April 2023.\n Publisher: De Gruyter\n\n\n\n
\n\n\n\n \n \n $\"Precision$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{noauthor_precision_2023,\n\ttitle = {Precision {Medicine}},\n\tvolume = {61},\n\tissn = {1437-4331},\n\turl = {https://www.degruyter.com/document/doi/10.1515/cclm-2023-7059/html?lang=en},\n\tdoi = {10.1515/cclm-2023-7059},\n\tabstract = {Article Precision Medicine was published on May 1, 2023 in the journal Clinical Chemistry and Laboratory Medicine (CCLM) (volume 61, issue s1).},\n\tlanguage = {en},\n\tnumber = {s1},\n\turldate = {2023-05-10},\n\tjournal = {Clinical Chemistry and Laboratory Medicine (CCLM)},\n\tmonth = apr,\n\tyear = {2023},\n\tnote = {Publisher: De Gruyter},\n\tkeywords = {DDM, DDM v.4, DDM-v4},\n\tpages = {s1925--s1960},\n}\n\n

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\n \n\n \n \n \n \n \n \n Genetic testing in children with Brugada syndrome: results from a large prospective registry.\n \n \n \n \n\n\n \n Pannone, L.; Bisignani, A.; Osei, R.; Gauthey, A.; Sorgente, A.; Vergara, P.; Monaco, C.; Della Rocca, D. G.; Del Monte, A.; Strazdas, A.; Mojica, J.; Al Housari, M.; Miraglia, V.; Mouram, S.; Paparella, G.; Ramak, R.; Overeinder, I.; Bala, G.; Almorad, A.; Ströker, E.; Pappaert, G.; Sieira, J.; De Ravel, T.; La Meir, M.; Brugada, P.; Chierchia, G. B.; Van Dooren, S.; and De Asmundis, C.\n\n\n \n\n\n\n EP Europace,euad079. April 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Genetic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{pannone_genetic_2023,\n\ttitle = {Genetic testing in children with {Brugada} syndrome: results from a large prospective registry},\n\tissn = {1099-5129, 1532-2092},\n\tshorttitle = {Genetic testing in children with {Brugada} syndrome},\n\turl = {https://academic.oup.com/europace/advance-article/doi/10.1093/europace/euad079/7113324},\n\tdoi = {10.1093/europace/euad079},\n\tabstract = {Abstract\n            \n              Aims\n              A pathogenic/likely pathogenic (P/LP) variant in SCN5A is found in 20–25\\% of patients with Brugada syndrome (BrS). However, the diagnostic yield and prognosis of gene panel testing in paediatric BrS is unclear. The aim of this study is to define the diagnostic yield and outcomes of SCN5A gene testing with ACMG variant classification in paediatric BrS patients compared with adults.\n            \n            \n              Methods and results\n              All consecutive patients diagnosed with BrS, between 1992 and 2022, were prospectively enrolled in the UZ Brussel BrS registry. Inclusion criteria were: (i) BrS diagnosis; (ii) genetic analysis performed with a large gene panel; and (iii) classification of gene variants following ACMG guidelines. Paediatric patients were defined as ≤16 years of age. The primary endpoint was ventricular arrhythmias (VAs). A total of 500 BrS patients were included, with 63 paediatric patients and 437 adult patients. Among children with BrS, 29 patients (46\\%) had a P/LP variant (P+) in SCN5A and no variants were found in 34 (54\\%) patients (P−). After a mean follow-up of 125.9 months, 8 children (12.7\\%) experienced a VA, treated with implanted cardioverter defibrillator shock. At survival analysis, P− paediatric patients had higher VA-free survival during the follow-up, compared with P+ paediatric patients. P+ status was an independent predictor of VA. There was no difference in VA-free survival between paediatric and adult BrS patients for both P− and P+.\n            \n            \n              Conclusion\n              In a large BrS cohort, the diagnostic yield for P/LP variants in the paediatric population is 46\\%. P+ children with BrS have a worse arrhythmic prognosis.},\n\tlanguage = {en},\n\turldate = {2023-05-10},\n\tjournal = {EP Europace},\n\tauthor = {Pannone, Luigi and Bisignani, Antonio and Osei, Randy and Gauthey, Anaïs and Sorgente, Antonio and Vergara, Pasquale and Monaco, Cinzia and Della Rocca, Domenico Giovanni and Del Monte, Alvise and Strazdas, Antanas and Mojica, Joerelle and Al Housari, Maysam and Miraglia, Vincenzo and Mouram, Sahar and Paparella, Gaetano and Ramak, Robbert and Overeinder, Ingrid and Bala, Gezim and Almorad, Alexandre and Ströker, Erwin and Pappaert, Gudrun and Sieira, Juan and De Ravel, Thomy and La Meir, Mark and Brugada, Pedro and Chierchia, Gian Battista and Van Dooren, Sonia and De Asmundis, Carlo},\n\tmonth = apr,\n\tyear = {2023},\n\tkeywords = {Alamut Visual Plus, Alamut Visual Plus v.1.4},\n\tpages = {euad079},\n}\n\n

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\n \n\n \n \n \n \n \n \n A Novel Alu Element Insertion in ATM Induces Exon Skipping in Suspected HBOC Patients.\n \n \n \n \n\n\n \n \n\n\n \n\n\n\n April 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@misc{noauthor_novel_2023,\n\ttitle = {A {Novel} {Alu} {Element} {Insertion} in {ATM} {Induces} {Exon} {Skipping} in {Suspected} {HBOC} {Patients}},\n\turl = {https://www.hindawi.com/journals/humu/2023/6623515/},\n\tmonth = apr,\n\tyear = {2023},\n}\n\n

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\n \n\n \n \n \n \n \n \n Neck Ganglioneuroma Mimicking a Thyroid Nodule in a Four-year-old Child: A Case Report and Review of the Literature.\n \n \n \n \n\n\n \n Corrado, S.; Morgante, C.; Tassi, S.; Maccarrone, F.; Massa, G. D.; Pontecorvi, A.; and Papi, G.\n\n\n \n\n\n\n International Journal of Endocrinology and Metabolism, In Press(In Press). April 2023.\n Number: In Press Publisher: Brieflands\n\n\n\n
\n\n\n\n \n \n $\"Neck$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{corrado_neck_2023,\n\ttitle = {Neck {Ganglioneuroma} {Mimicking} a {Thyroid} {Nodule} in a {Four}-year-old {Child}: {A} {Case} {Report} and {Review} of the {Literature}},\n\tvolume = {In Press},\n\tcopyright = {This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.},\n\tissn = {1726-9148},\n\tshorttitle = {Neck {Ganglioneuroma} {Mimicking} a {Thyroid} {Nodule} in a {Four}-year-old {Child}},\n\turl = {https://brieflands.com/articles/ijem-126486.html#abstract},\n\tdoi = {10.5812/ijem-126486},\n\tabstract = {Introduction: Ganglioneuromas are tumors of neurogenic origin usually located in the abdomen, the adrenal glands, and the mediastinum but infrequently found in the neck region. Case Presentation: We describe the case of a four-year-old Albanian girl presenting with an anterior neck mass initially suspected to be a thyroid nodule. From a clinical point of view, there was no evidence of compression on vital cervical structures. Lab tests detected normal serum thyrotropin, calcitonin, and parathormone concentrations. A neck ultrasound showed a huge mass apparently originating from the left thyroid lobe. Cytological examination of fine needle biopsy demonstrated a population of large cells with eosinophilic cytoplasm, regular nuclei, and prominent nucleoli and spindle cells without significant atypia, consistent with a benign lesion of neurogenic origin. Also, the neck MRI displayed a mass with well-defined margins, likely arising from the peripheral nervous system. The patient underwent surgical excision of the mass without complications. The histological exam was diagnostic for ganglioneuroma. Conclusions: We discuss the cytological and histological features peculiar to such a rare neck lesion and review the differential diagnosis.},\n\tlanguage = {en},\n\tnumber = {In Press},\n\turldate = {2023-05-10},\n\tjournal = {International Journal of Endocrinology and Metabolism},\n\tauthor = {Corrado, Stefania and Morgante, Cesare and Tassi, Sauro and Maccarrone, Francesco and Massa, Gianluca Di and Pontecorvi, Alfredo and Papi, Giampaolo},\n\tmonth = apr,\n\tyear = {2023},\n\tnote = {Number: In Press\nPublisher: Brieflands},\n\tkeywords = {CES, DDM},\n}\n\n

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\n \n\n \n \n \n \n \n \n Abstract 6085: Molecular profile by next generation sequencing in papillary thyroid carcinoma, Colombian Cohort at Fundacion Santa fe de Bogota University Hospital.\n \n \n \n \n\n\n \n Rodriguez, P.; González, S.; Cruz, S.; Juez, Y.; Becerra, D.; Baldión, M.; Perdomo, S.; Beltran, A.; Hakim, J.; and Gonzales, D.\n\n\n \n\n\n\n Cancer Research, 83(7_Supplement): 6085. April 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Abstract$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{rodriguez_abstract_2023,\n\ttitle = {Abstract 6085: {Molecular} profile by next generation sequencing in papillary thyroid carcinoma, {Colombian} {Cohort} at {Fundacion} {Santa} fe de {Bogota} {University} {Hospital}},\n\tvolume = {83},\n\tissn = {0008-5472},\n\tshorttitle = {Abstract 6085},\n\turl = {https://doi.org/10.1158/1538-7445.AM2023-6085},\n\tdoi = {10.1158/1538-7445.AM2023-6085},\n\tabstract = {Objective/aim: To describe the main molecular alterations in a Colombian Cohort of patients diagnosed with Papillary Thyroid Carcinoma (PTC) at Fundacion Santa Fe de Bogota University Hospital between 1993 and 2011Methods: A total of 231 surgically intervened patients at our institution and diagnosed with PTC with available paraffin blocks were analysed. DNA and RNA extraction was performed from FFPE samples using Quick-DNA \\&amp; RNA FFPE MiniPrep Kit (Zymo Research). Next Generation Sequencing analysis was performed using SOPHiA Solid Tumor Solutions Kit (SOPHiA GENETICS, Saint Sulpice, Suiza), which detects 42 DNA genes and 137 fusion genes with the platform MiSeq System (Illlumina, San Diego, California). Data underwent QA and QC and variants were analysed through Sophia commercial pipeline for somatic aberrations.Results: Among 231 patients, 82\\% were women, average age 45 +/- 13 y-o, 97\\% from Colombia, with institutional pathologic diagnosis of PTC. The most frequent histological subtypes were Classic PTG (33\\%), Follicular Infiltrative (29\\%) and Tall cell (23\\%). Identification of clinically relevant molecular alterations was done (see table 1). The most frequent SNV mutations were BRAF-V600E (72\\%), TP53 (9\\%) and IDH1-R132H (8\\%). The most frequent insertions or deletions (INDELS) were found in KIT (75\\%). We identified 8 fusion genes (most frequent were RET-CCD6 and ETV6-NTRK3). Interestingly, we detected 3 MSI positive cases.Conclusions: PTC molecular profile by NGS can allow us to improve molecular understanding of the disease and identify possible prognostic factors and treatment targets.Table 1.Molecular alterations detected by next-generation sequencing in Papillary carcinomaMolecular alterationsGenen\\%INDEL (n=20)KIT1575,0NRAS15,0PTPN1115,0TP53315SNV (n=226)BRAF16372,1FGFR110,4HRAS20,9IDH1198,4KIT20,9KRAS20,9NRAS94,0PDGFRA10,4PIK3CA31,3SMAD441,8TP53208,8Fusion genes (n=6)CCDC6-RET225,0ETV6-NTRK3225,0GOLGB1-TACC3112,5MYH14-BICC1225,0GOPC-RET112,5MSI (n=231)MSI-L31,3Negative22898,7Citation Format: Paula Rodriguez, Sebastián González, Sergio Cruz, Yesith Juez, David Becerra, Margarita Baldión, Sandra Perdomo, Angela Beltran, Jose Hakim, Deyanira Gonzales. Molecular profile by next generation sequencing in papillary thyroid carcinoma, Colombian Cohort at Fundacion Santa fe de Bogota University Hospital [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7\\_Suppl):Abstract nr 6085.},\n\tnumber = {7\\_Supplement},\n\turldate = {2023-05-10},\n\tjournal = {Cancer Research},\n\tauthor = {Rodriguez, Paula and González, Sebastián and Cruz, Sergio and Juez, Yesith and Becerra, David and Baldión, Margarita and Perdomo, Sandra and Beltran, Angela and Hakim, Jose and Gonzales, Deyanira},\n\tmonth = apr,\n\tyear = {2023},\n\tkeywords = {Commercial pipeline, DDM, Pipeline for somatic aberrations, STS, Solid Tumor Solution, Somatic aberrations},\n\tpages = {6085},\n}\n\n

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\n Objective/aim: To describe the main molecular alterations in a Colombian Cohort of patients diagnosed with Papillary Thyroid Carcinoma (PTC) at Fundacion Santa Fe de Bogota University Hospital between 1993 and 2011Methods: A total of 231 surgically intervened patients at our institution and diagnosed with PTC with available paraffin blocks were analysed. DNA and RNA extraction was performed from FFPE samples using Quick-DNA & RNA FFPE MiniPrep Kit (Zymo Research). Next Generation Sequencing analysis was performed using SOPHiA Solid Tumor Solutions Kit (SOPHiA GENETICS, Saint Sulpice, Suiza), which detects 42 DNA genes and 137 fusion genes with the platform MiSeq System (Illlumina, San Diego, California). Data underwent QA and QC and variants were analysed through Sophia commercial pipeline for somatic aberrations.Results: Among 231 patients, 82% were women, average age 45 +/- 13 y-o, 97% from Colombia, with institutional pathologic diagnosis of PTC. The most frequent histological subtypes were Classic PTG (33%), Follicular Infiltrative (29%) and Tall cell (23%). Identification of clinically relevant molecular alterations was done (see table 1). The most frequent SNV mutations were BRAF-V600E (72%), TP53 (9%) and IDH1-R132H (8%). The most frequent insertions or deletions (INDELS) were found in KIT (75%). We identified 8 fusion genes (most frequent were RET-CCD6 and ETV6-NTRK3). Interestingly, we detected 3 MSI positive cases.Conclusions: PTC molecular profile by NGS can allow us to improve molecular understanding of the disease and identify possible prognostic factors and treatment targets.Table 1.Molecular alterations detected by next-generation sequencing in Papillary carcinomaMolecular alterationsGenen%INDEL (n=20)KIT1575,0NRAS15,0PTPN1115,0TP53315SNV (n=226)BRAF16372,1FGFR110,4HRAS20,9IDH1198,4KIT20,9KRAS20,9NRAS94,0PDGFRA10,4PIK3CA31,3SMAD441,8TP53208,8Fusion genes (n=6)CCDC6-RET225,0ETV6-NTRK3225,0GOLGB1-TACC3112,5MYH14-BICC1225,0GOPC-RET112,5MSI (n=231)MSI-L31,3Negative22898,7Citation Format: Paula Rodriguez, Sebastián González, Sergio Cruz, Yesith Juez, David Becerra, Margarita Baldión, Sandra Perdomo, Angela Beltran, Jose Hakim, Deyanira Gonzales. Molecular profile by next generation sequencing in papillary thyroid carcinoma, Colombian Cohort at Fundacion Santa fe de Bogota University Hospital [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6085.\n

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\n \n\n \n \n \n \n \n \n Clinical significance of hypouricemia in children and adolescents.\n \n \n \n \n\n\n \n Köksoy, A. Y.; Görükmez, Ö.; and Dorum, S.\n\n\n \n\n\n\n Pediatric Nephrology. March 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Clinical$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{koksoy_clinical_2023,\n\ttitle = {Clinical significance of hypouricemia in children and adolescents},\n\tissn = {1432-198X},\n\turl = {https://doi.org/10.1007/s00467-023-05948-4},\n\tdoi = {10.1007/s00467-023-05948-4},\n\tabstract = {Although hyperuricemia is a widely studied condition with well-known effects on the kidneys, hypouricemia is usually considered a biochemical abnormality of no clinical significance despite the fact that it can be a sign or major finding of serious metabolic or genetic diseases affecting kidney health. In this study, we aimed to investigate and emphasize the clinical significance of hypouricemia.},\n\tlanguage = {en},\n\turldate = {2023-05-10},\n\tjournal = {Pediatric Nephrology},\n\tauthor = {Köksoy, Adem Yasin and Görükmez, Özlem and Dorum, Sevil},\n\tmonth = mar,\n\tyear = {2023},\n\tkeywords = {CES v2, DDM},\n}\n\n

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\n \n\n \n \n \n \n \n \n Association of a Novel Homozygous Variant in ABCA1 Gene with Tangier Disease.\n \n \n \n \n\n\n \n Barbosa-Gouveia, S.; Fernández-Crespo, S.; Lazaré-Iglesias, H.; González-Quintela, A.; Vázquez-Agra, N.; and Hermida-Ameijeiras, Á.\n\n\n \n\n\n\n Journal of Clinical Medicine, 12(7): 2596. March 2023.\n Number: 7 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Association$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{barbosa-gouveia_association_2023,\n\ttitle = {Association of a {Novel} {Homozygous} {Variant} in {ABCA1} {Gene} with {Tangier} {Disease}},\n\tvolume = {12},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2077-0383},\n\turl = {https://www.mdpi.com/2077-0383/12/7/2596},\n\tdoi = {10.3390/jcm12072596},\n\tabstract = {Tangier disease (TD) is a rare autosomal recessive disorder caused by a variant in the ABCA1 gene, characterized by significantly reduced levels of plasma high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (ApoA-I). TD typically leads to accumulation of cholesterol in the peripheral tissues and early coronary disease but with highly variable clinical expression. Herein, we describe a case study of a 59-year-old male patient with features typical of TD, in whom a likely pathogenic variant in the ABCA1 gene was identified by whole-exome sequencing (WES), identified for the first time as homozygous (NM\\_005502.4: c.4799A{\\textgreater}G (p. His1600Arg)). In silico analysis including MutationTaster and DANN score were used to predict the pathogenicity of the variant and a protein model generated by SWISS-MODEL was built to determine how the homozygous variant detected in our patient may change the protein structure and impact on its function. This case study describes a homozygous variant of the ABCA1 gene, which is responsible for a severe form of TD and underlines the importance of using bioinformatics and genomics for linking genotype to phenotype and better understanding and accounting for the functional impact of genetic variations.},\n\tlanguage = {en},\n\tnumber = {7},\n\turldate = {2023-05-10},\n\tjournal = {Journal of Clinical Medicine},\n\tauthor = {Barbosa-Gouveia, Sofía and Fernández-Crespo, Silvia and Lazaré-Iglesias, Héctor and González-Quintela, Arturo and Vázquez-Agra, Néstor and Hermida-Ameijeiras, Álvaro},\n\tmonth = mar,\n\tyear = {2023},\n\tnote = {Number: 7\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {ABCA1, ApoA-I, DDM, DDM v4.7.5, Human Core Exome Kit, Twist Bioscience},\n\tpages = {2596},\n}\n\n

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\n \n\n \n \n \n \n \n \n Clinical exome sequencing findings in 1589 patients.\n \n \n \n \n\n\n \n Gorukmez, O.; Gorukmez, O.; and Topak, A.\n\n\n \n\n\n\n American Journal of Medical Genetics Part A, 191(6): 1557–1564. March 2023.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajmg.a.63190\n\n\n\n
\n\n\n\n \n \n $\"Clinical$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{gorukmez_clinical_2023,\n\ttitle = {Clinical exome sequencing findings in 1589 patients},\n\tvolume = {191},\n\tissn = {1552-4833},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.63190},\n\tdoi = {10.1002/ajmg.a.63190},\n\tabstract = {Clinical exome sequencing (CES) is important for the diagnosis of Mendelian diseases, which are clinically and etiologically heterogeneous. Sharing of large amounts of CES data associated with clinical findings will increase the accuracy of variant interpretation. We performed a retrospective study to state the diagnostic yield of CES in 1589 patients with a wide phenotypic spectrum. CES was performed using the Sophia Clinical Exome Sequencing Kit with 4493 genes, followed by sequencing on a NextSeq 500 system. The diagnosis rate was 36.8\\% when only pathogenic and likely pathogenic variants were included. Consanguineous unions and positive family history were associated with a high diagnostic yield. The neurological disease group had the highest number of patients. The groups with high diagnosis rates were ear, eye, and muscle disease groups. Seven candidate genes (EFHC2, HSPB3, FAAH2, ITGB1, GYG2, CD177, and CSTF2T) that are not yet associated with human diseases were identified. Owing to the high diagnostic yield of CES compared with that of other genetic tests, it can be used as a standard diagnostic test in patients with rare genetic disorders that require a wide differential diagnosis, especially in laboratories with limited resources.},\n\tlanguage = {en},\n\tnumber = {6},\n\turldate = {2023-05-10},\n\tjournal = {American Journal of Medical Genetics Part A},\n\tauthor = {Gorukmez, Ozlem and Gorukmez, Orhan and Topak, Ali},\n\tmonth = mar,\n\tyear = {2023},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajmg.a.63190},\n\tkeywords = {CES, Mendelian disorders},\n\tpages = {1557--1564},\n}\n\n

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\n \n\n \n \n \n \n \n \n Genomic profile of two Brazilian choroid plexus tumors by whole-exome sequencing.\n \n \n \n \n\n\n \n Garcia, F. A. D. O.; Evangelista, A. F.; Mançano, B. M.; Moreno, D. A.; Berardinelli, G. N.; De Paula, F. E.; Antoniazzi, A. P.; Júnior, C. A.; Lombardi, I.; Santana, I.; Teixeira, G. R.; Costa, C. E.; and Reis, R. M.\n\n\n \n\n\n\n Molecular Case Studies, 9(1): a006245. March 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Genomic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{garcia_genomic_2023,\n\ttitle = {Genomic profile of two {Brazilian} choroid plexus tumors by whole-exome sequencing},\n\tvolume = {9},\n\tissn = {2373-2865, 2373-2873},\n\turl = {http://molecularcasestudies.cshlp.org/lookup/doi/10.1101/mcs.a006245},\n\tdoi = {10.1101/mcs.a006245},\n\tabstract = {Choroid plexus tumors (CPTs) are rare intracranial neoplasms, representing {\\textless}1\\% of all brain tumors, yet they represent 20\\% of first-year pediatric brain tumors. Although these tumors have been linked to TP53 germline mutations in the context of Li–Fraumeni syndrome, their somatic driver alterations remain poorly understood. In this study, we report two cases of lateral ventricle tumors: 3-yr-old male diagnosed with an atypical choroid plexus papilloma (aCPP), and a 6-mo-old female diagnosed with a choroid plexus carcinoma (CPC). We performed whole-exome sequencing of paired blood and tumor tissue in both patients, categorized somatic variants, and determined copy-number alterations. Our analysis revealed a tier II variant (Association for Molecular Pathology [AMP] criteria) in BRD1, a H3 and TP53 acetylation agent, in the aCPP. In addition, we detected copy-number gains on Chromosomes 12, 18, and 20 and copy-number losses on Chromosomes 13q and 22q (BRD1 locus) in this tumor. The CPC tumor had only a pathogenic germline TP53 variant, based on American College of Medical Genetics (ACMG) criteria, with a clinical and familiar history of Li–Fraumeni syndrome. The CPC patient presented loss of heterozygosity (LoH) of TP53 loci and hyperdiploid genome. Both tumors were microsatellite-stable. This is the first study performing whole-exome sequencing in Brazilian choroid plexus tumors, and in line with the literature, we corroborate the absence of recurrent somatic mutations in these tumors. Further studies with larger sample sizes are necessary to confirm our findings and better understand the underlying biology of these tumors.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2023-05-10},\n\tjournal = {Molecular Case Studies},\n\tauthor = {Garcia, Felipe Antonio De Oliveira and Evangelista, Adriane Feijó and Mançano, Bruna Minniti and Moreno, Daniel Antunes and Berardinelli, Gustavo Noriz and De Paula, Flávia Escremim and Antoniazzi, Augusto Perazzolo and Júnior, Carlos Almeida and Lombardi, Ismael and Santana, Iara and Teixeira, Gustavo Ramos and Costa, Caio Evangelista and Reis, Rui Manuel},\n\tmonth = mar,\n\tyear = {2023},\n\tkeywords = {WES},\n\tpages = {a006245},\n}\n\n

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\n \n\n \n \n \n \n \n \n Germline Variants in MLH1 and ATM Genes in a Young Patient with MSI-H in a Precancerous Colonic Lesion.\n \n \n \n \n\n\n \n Nolano, A.; Rossi, G. B.; D’Angelo, V.; Liccardo, R.; Rosa, M. D.; Izzo, P.; and Duraturo, F.\n\n\n \n\n\n\n International Journal of Molecular Sciences, 24(6): 5970. March 2023.\n Number: 6 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Germline$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{nolano_germline_2023,\n\ttitle = {Germline {Variants} in {MLH1} and {ATM} {Genes} in a {Young} {Patient} with {MSI}-{H} in a {Precancerous} {Colonic} {Lesion}},\n\tvolume = {24},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {1422-0067},\n\turl = {https://www.mdpi.com/1422-0067/24/6/5970},\n\tdoi = {10.3390/ijms24065970},\n\tabstract = {Lynch syndrome (LS) is an autosomal dominant inherited disorder that primarily predisposes individuals to colorectal and endometrial cancer. It is associated with pathogenic variants in DNA mismatch repair (MMR) genes. In this study, we report the case of a 16-year-old boy who developed a precancerous colonic lesion and had a clinical suspicion of LS. The proband was found to have a somatic MSI-H status. Analysis of the coding sequences and flanking introns of the MLH1 and MSH2 genes by Sanger sequencing led to the identification of the variant of uncertain significance, namely, c.589-9\\_589-6delGTTT in the MLH1 gene. Further investigation revealed that this variant was likely pathogenetic. Subsequent next-generation sequencing panel analysis revealed the presence of two variants of uncertain significance in the ATM gene. We conclude that the phenotype of our index case is likely the result of a synergistic effect of these identified variants. Future studies will allow us to understand how risk alleles in different colorectal-cancer-prone genes interact with each other to increase an individual’s risk of developing cancer.},\n\tlanguage = {en},\n\tnumber = {6},\n\turldate = {2023-05-10},\n\tjournal = {International Journal of Molecular Sciences},\n\tauthor = {Nolano, Antonio and Rossi, Giovanni Battista and D’Angelo, Valentina and Liccardo, Raffaella and Rosa, Marina De and Izzo, Paola and Duraturo, Francesca},\n\tmonth = mar,\n\tyear = {2023},\n\tnote = {Number: 6\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {DDM, HCS, Lynch syndrome},\n\tpages = {5970},\n}\n\n

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\n \n\n \n \n \n \n \n \n Prevalence of Germline Mutations in Cancer Predisposition Genes in Patients with Pancreatic Cancer or Suspected Related Hereditary Syndromes: Historical Prospective Analysis.\n \n \n \n \n\n\n \n Dal Buono, A.; Poliani, L.; Greco, L.; Bianchi, P.; Barile, M.; Giatti, V.; Bonifacio, C.; Carrara, S.; Malesci, A.; and Laghi, L.\n\n\n \n\n\n\n Cancers, 15(6): 1852. March 2023.\n Number: 6 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Prevalence$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{dal_buono_prevalence_2023,\n\ttitle = {Prevalence of {Germline} {Mutations} in {Cancer} {Predisposition} {Genes} in {Patients} with {Pancreatic} {Cancer} or {Suspected} {Related} {Hereditary} {Syndromes}: {Historical} {Prospective} {Analysis}},\n\tvolume = {15},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2072-6694},\n\tshorttitle = {Prevalence of {Germline} {Mutations} in {Cancer} {Predisposition} {Genes} in {Patients} with {Pancreatic} {Cancer} or {Suspected} {Related} {Hereditary} {Syndromes}},\n\turl = {https://www.mdpi.com/2072-6694/15/6/1852},\n\tdoi = {10.3390/cancers15061852},\n\tabstract = {We investigate the prevalence of germline mutations in cancer predisposition genes in patients with pancreatic ductal adenocarcinoma (PDAC) or suspected related hereditary syndromes. Methods: we enrolled for NGS with an Illumina TrueSight Cancer panel comprising 19 CPGs and 113 consecutive subjects referred to cancer genetic clinics for metastatic PDAC, early onset PDAC, suspected hereditary syndrome, or positive family history. Results: Overall, 23 (20.1\\%) subjects were carriers of 24 pathogenetic variants (PVs). We found 9 variants in BRCA2 (37.5\\%), 6 in CDKN2A (25\\%), 3 in ATM (12.5\\%), 2 in BRCA1 (8.3\\%), 1 in CHEK2 (4.1\\%), 1 in PALB2 (4.1\\%), 1 in MITF (4.1\\%), and 1 in FANCM (4.1\\%). A double PV (BRCA1 plus BRCA2) was found in 1 subject. We observed a nearly 30\\% (16/55) mutational rate in the subgroup of subjects tested for the suspected syndromes (PDAC and other synchronous or metachronous tumors or an indicative family history), and the frequency was significantly higher than that in patients with only metastatic PDAC (p = 0.05). In our cohort, 39 variants of unknown significance (VUS) were identified, most of which (16/39, 41\\%) in genes belonging to the Lynch syndrome spectrum. Conclusion: A clinically relevant proportion of pancreatic cancer is associated with mutations in known predisposition genes. Guidelines instructing on an adequate selection for accessing genetic testing are eagerly needed. The heterogeneity of mutations identified in this study reinforces the value of using a multiple-gene panel in pancreatic cancer.},\n\tlanguage = {en},\n\tnumber = {6},\n\turldate = {2023-05-10},\n\tjournal = {Cancers},\n\tauthor = {Dal Buono, Arianna and Poliani, Laura and Greco, Luana and Bianchi, Paolo and Barile, Monica and Giatti, Valentina and Bonifacio, Cristiana and Carrara, Silvia and Malesci, Alberto and Laghi, Luigi},\n\tmonth = mar,\n\tyear = {2023},\n\tnote = {Number: 6\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {DDM, germline mutation, hereditary syndrome, pancreatic cancer, pathogenic variant},\n\tpages = {1852},\n}\n\n

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\n \n\n \n \n \n \n \n \n Ruxolitinib in cytopenic myelofibrosis: Response, toxicity, drug discontinuation, and outcome.\n \n \n \n \n\n\n \n Palandri, F.; Breccia, M.; Mazzoni, C.; Auteri, G.; Elli, E. M.; Trawinska, M. M.; Polverelli, N.; Tiribelli, M.; Benevolo, G.; Iurlo, A.; Tieghi, A.; Heidel, F. H.; Caocci, G.; Beggiato, E.; Binotto, G.; Cavazzini, F.; Miglino, M.; Bosi, C.; Crugnola, M.; Bocchia, M.; Martino, B.; Pugliese, N.; Biondo, M.; Venturi, M.; Scaffidi, L.; Isidori, A.; Cattaneo, D.; Krampera, M.; Pane, F.; Cilloni, D.; Semenzato, G.; Lemoli, R. M.; Cuneo, A.; Abruzzese, E.; Bartoletti, D.; Paglia, S.; Vianelli, N.; Cavo, M.; Bonifacio, M.; and Palumbo, G. A.\n\n\n \n\n\n\n Cancer, 129(11): 1704–1713. March 2023.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.34722\n\n\n\n
\n\n\n\n \n \n $\"Ruxolitinib$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{palandri_ruxolitinib_2023,\n\ttitle = {Ruxolitinib in cytopenic myelofibrosis: {Response}, toxicity, drug discontinuation, and outcome},\n\tvolume = {129},\n\tissn = {1097-0142},\n\tshorttitle = {Ruxolitinib in cytopenic myelofibrosis},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/cncr.34722},\n\tdoi = {10.1002/cncr.34722},\n\tabstract = {Background Patients with cytopenic myelofibrosis (MF) have more limited therapeutic options and poorer prognoses compared with patients with the myeloproliferative phenotype. Aims and Methods Prognostic correlates of cytopenic phenotype were explored in 886 ruxolitinib-treated patients with primary/secondary MF (PMF/SMF) included in the RUX-MF retrospective study. Cytopenia was defined as: leukocyte count {\\textless}4 × 109/L and/or hemoglobin {\\textless}11/{\\textless}10 g/dL (males/females) and/or platelets {\\textless}100 × 109/L. Results Overall, 407 (45.9\\%) patients had a cytopenic MF, including 249 (52.4\\%) with PMF. In multivariable analysis, high molecular risk mutations (p = .04), intermediate 2/high Dynamic International Prognostic Score System (p {\\textless} .001) and intermediate 2/high Myelofibrosis Secondary to Polycythemia Vera and Essential Thrombocythemia Prognostic Model (p {\\textless} .001) remained associated with cytopenic MF in the overall cohort, PMF, and SMF, respectively. Patients with cytopenia received lower average ruxolitinib at the starting (25.2 mg/day vs. 30.2 mg/day, p {\\textless} .001) and overall doses (23.6 mg/day vs. 26.8 mg/day, p {\\textless} .001) and achieved lower rates of spleen (26.5\\% vs. 34.1\\%, p = .04) and symptom (59.8\\% vs. 68.8\\%, p = .008) responses at 6 months compared with patients with the proliferative phenotype. Patients with cytopenia also had higher rates of thrombocytopenia at 3 months (31.1\\% vs. 18.8\\%, p {\\textless} .001) but lower rates of anemia (65.6\\% vs. 57.7\\%, p = .02 at 3 months and 56.6\\% vs. 23.9\\% at 6 months, p {\\textless} .001). After competing risk analysis, the cumulative incidence of ruxolitinib discontinuation at 5 years was 57\\% and 38\\% in patients with cytopenia and the proliferative phenotype (p {\\textless} .001), whereas cumulative incidence of leukemic transformation was similar (p = .06). In Cox regression analysis adjusted for Dynamic International Prognostic Score System score, survival was significantly shorter in patients with cytopenia (p {\\textless} .001). Conclusions Cytopenic MF has a lower probability of therapeutic success with ruxolitinib as monotherapy and worse outcome. These patients should be considered for alternative therapeutic strategies.},\n\tlanguage = {en},\n\tnumber = {11},\n\turldate = {2023-05-10},\n\tjournal = {Cancer},\n\tauthor = {Palandri, Francesca and Breccia, Massimo and Mazzoni, Camilla and Auteri, Giuseppe and Elli, Elena Maria and Trawinska, Malgorzata M. and Polverelli, Nicola and Tiribelli, Mario and Benevolo, Giulia and Iurlo, Alessandra and Tieghi, Alessia and Heidel, Florian H. and Caocci, Giovanni and Beggiato, Eloise and Binotto, Gianni and Cavazzini, Francesco and Miglino, Maurizio and Bosi, Costanza and Crugnola, Monica and Bocchia, Monica and Martino, Bruno and Pugliese, Novella and Biondo, Mattia and Venturi, Marta and Scaffidi, Luigi and Isidori, Alessandro and Cattaneo, Daniele and Krampera, Mauro and Pane, Fabrizio and Cilloni, Daniela and Semenzato, Gianpietro and Lemoli, Roberto M. and Cuneo, Antonio and Abruzzese, Elisabetta and Bartoletti, Daniela and Paglia, Simona and Vianelli, Nicola and Cavo, Michele and Bonifacio, Massimiliano and Palumbo, Giuseppe A.},\n\tmonth = mar,\n\tyear = {2023},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.34722},\n\tkeywords = {Myeloid Solution Panel, NGS, NGS-next generation sequencing},\n\tpages = {1704--1713},\n}\n\n

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\n Background Patients with cytopenic myelofibrosis (MF) have more limited therapeutic options and poorer prognoses compared with patients with the myeloproliferative phenotype. Aims and Methods Prognostic correlates of cytopenic phenotype were explored in 886 ruxolitinib-treated patients with primary/secondary MF (PMF/SMF) included in the RUX-MF retrospective study. Cytopenia was defined as: leukocyte count \\textless4 × 109/L and/or hemoglobin \\textless11/\\textless10 g/dL (males/females) and/or platelets \\textless100 × 109/L. Results Overall, 407 (45.9%) patients had a cytopenic MF, including 249 (52.4%) with PMF. In multivariable analysis, high molecular risk mutations (p = .04), intermediate 2/high Dynamic International Prognostic Score System (p \\textless .001) and intermediate 2/high Myelofibrosis Secondary to Polycythemia Vera and Essential Thrombocythemia Prognostic Model (p \\textless .001) remained associated with cytopenic MF in the overall cohort, PMF, and SMF, respectively. Patients with cytopenia received lower average ruxolitinib at the starting (25.2 mg/day vs. 30.2 mg/day, p \\textless .001) and overall doses (23.6 mg/day vs. 26.8 mg/day, p \\textless .001) and achieved lower rates of spleen (26.5% vs. 34.1%, p = .04) and symptom (59.8% vs. 68.8%, p = .008) responses at 6 months compared with patients with the proliferative phenotype. Patients with cytopenia also had higher rates of thrombocytopenia at 3 months (31.1% vs. 18.8%, p \\textless .001) but lower rates of anemia (65.6% vs. 57.7%, p = .02 at 3 months and 56.6% vs. 23.9% at 6 months, p \\textless .001). After competing risk analysis, the cumulative incidence of ruxolitinib discontinuation at 5 years was 57% and 38% in patients with cytopenia and the proliferative phenotype (p \\textless .001), whereas cumulative incidence of leukemic transformation was similar (p = .06). In Cox regression analysis adjusted for Dynamic International Prognostic Score System score, survival was significantly shorter in patients with cytopenia (p \\textless .001). Conclusions Cytopenic MF has a lower probability of therapeutic success with ruxolitinib as monotherapy and worse outcome. These patients should be considered for alternative therapeutic strategies.\n

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\n \n\n \n \n \n \n \n \n A Case of Mucopolysaccharidosis II Caused by a Novel Variant with Skin Linear Hyperpigmented Streaks along Blaschko’s Lines.\n \n \n \n \n\n\n \n Sofronova, V.; Gurinova, E.; Petukhova, D.; Fukamatsu, H.; Yamamoto, T.; Aoyama, Y.; Golikova, P.; Moskvitin, G.; Ivanova, R.; Savvina, M.; Vasilev, F.; Moriwaki, T.; Terawaki, S.; Sukhomyasova, A.; Maksimova, N.; and Otomo, T.\n\n\n \n\n\n\n International Journal of Molecular Sciences, 24(6): 5647. March 2023.\n Number: 6 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{sofronova_case_2023,\n\ttitle = {A {Case} of {Mucopolysaccharidosis} {II} {Caused} by a {Novel} {Variant} with {Skin} {Linear} {Hyperpigmented} {Streaks} along {Blaschko}’s {Lines}},\n\tvolume = {24},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {1422-0067},\n\turl = {https://www.mdpi.com/1422-0067/24/6/5647},\n\tdoi = {10.3390/ijms24065647},\n\tabstract = {We report a case of an eight-year-old boy with mucopolysaccharidosis (MPS) II with atypical skin lesions of hyperpigmented streaks along Blaschko’s lines. This case presented with mild symptoms of MPS such as hepatosplenomegaly, joint stiffness, and quite mild bone deformity, which was the reason for the delay in diagnosis until the age of seven years. However, he showed an intellectual disability that did not meet the diagnostic criteria for an attenuated form of MPS II. Iduronate 2-sulfatase activity was reduced. Clinical exome sequencing of DNA from peripheral blood revealed a novel pathogenic missense variant (NM\\_000202.8(IDS\\_v001):c.703C{\\textgreater}A, p.(Pro235Thr)) in the IDS gene, which was confirmed in the mother with a heterozygous state. His brownish skin lesions differed from the Mongolian blue spots or “pebbling” of the skin that are observed in MPS II.},\n\tlanguage = {en},\n\tnumber = {6},\n\turldate = {2023-05-10},\n\tjournal = {International Journal of Molecular Sciences},\n\tauthor = {Sofronova, Viktoriia and Gurinova, Elizaveta and Petukhova, Diana and Fukamatsu, Hiroko and Yamamoto, Takenobu and Aoyama, Yumi and Golikova, Polina and Moskvitin, Gavril and Ivanova, Roza and Savvina, Mira and Vasilev, Filipp and Moriwaki, Takahito and Terawaki, Seigo and Sukhomyasova, Aitalina and Maksimova, Nadezhda and Otomo, Takanobu},\n\tmonth = mar,\n\tyear = {2023},\n\tnote = {Number: 6\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {CES v2, Hunter syndrome, mucopolysaccharidosis II, skin pigmentation},\n\tpages = {5647},\n}\n\n

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\n \n\n \n \n \n \n \n \n Long-term survival in patients with IDH-wildtype glioblastoma: clinical and molecular characteristics.\n \n \n \n \n\n\n \n Chehade, G.; Lawson, T. M.; Lelotte, J.; Daoud, L.; Di Perri, D.; Whenham, N.; Duprez, T.; Tajeddine, N.; Tissir, F.; and Raftopoulos, C.\n\n\n \n\n\n\n Acta Neurochirurgica, 165(4): 1075–1085. March 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Long-term$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{chehade_long-term_2023,\n\ttitle = {Long-term survival in patients with {IDH}-wildtype glioblastoma: clinical and molecular characteristics},\n\tvolume = {165},\n\tissn = {0942-0940},\n\tshorttitle = {Long-term survival in patients with {IDH}-wildtype glioblastoma},\n\turl = {https://doi.org/10.1007/s00701-023-05544-3},\n\tdoi = {10.1007/s00701-023-05544-3},\n\tabstract = {Glioblastoma is an aggressive tumor that has a dismal prognosis even with multimodal treatment. However, some patients survive longer than expected. The objective of this study was to revisit patients diagnosed with glioblastoma according to the 2021 WHO classification and analyze clinical and molecular characteristics associated with long-term survival (LTS).},\n\tlanguage = {en},\n\tnumber = {4},\n\turldate = {2023-05-09},\n\tjournal = {Acta Neurochirurgica},\n\tauthor = {Chehade, Georges and Lawson, Tévi Morel and Lelotte, Julie and Daoud, Lina and Di Perri, Dario and Whenham, Nicolas and Duprez, Thierry and Tajeddine, Nicolas and Tissir, Fadel and Raftopoulos, Christian},\n\tmonth = mar,\n\tyear = {2023},\n\tkeywords = {DDM, Glioblastoma, o(6)-methylguanine-DNA methyltransferase},\n\tpages = {1075--1085},\n}\n\n

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\n \n\n \n \n \n \n \n \n SARS-CoV-2 coinfection in immunocompromised host leads to the generation of recombinant strain.\n \n \n \n \n\n\n \n Zannoli, S.; Brandolini, M.; Marino, M. M.; Denicolò, A.; Mancini, A.; Taddei, F.; Arfilli, V.; Manera, M.; Gatti, G.; Battisti, A.; Grumiro, L.; Scalcione, A.; Dirani, G.; and Sambri, V.\n\n\n \n\n\n\n International Journal of Infectious Diseases, 131: 65–70. March 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"SARS-CoV-2$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{zannoli_sars-cov-2_2023,\n\ttitle = {{SARS}-{CoV}-2 coinfection in immunocompromised host leads to the generation of recombinant strain},\n\tvolume = {131},\n\tissn = {1201-9712},\n\turl = {https://www.sciencedirect.com/science/article/pii/S1201971223000887},\n\tdoi = {10.1016/j.ijid.2023.03.014},\n\tabstract = {Objectives\nRecombination related to coinfection is a huge driving force in determining the virus genetic variability, particularly in conditions of partial immune control, leading to prolonged infection. Here, we characterized a distinctive mutational pattern, highly suggestive of Delta-Omicron double infection, in a lymphoma patient.\nMethods\nThe specimen was characterized through a combined approach, analyzing the results of deep sequencing in primary sample, viral culture, and plaque assay.\nResults\nBioinformatic analysis on the sequences deriving from the primary sample supports the hypothesis of a double viral population within the host. Plaque assay on viral culture led to the isolation of a recombinant strain deriving from Delta and Omicron lineages, named XS, which virtually replaced its parent lineages within a single viral propagation.\nConclusion\nIt is impossible to establish whether the recombination event happened within the host or in vitro; however, it is important to monitor co-infections, especially in the exceptional intrahost environment of patients who are immunocompromised, as strong driving forces of viral evolution.},\n\tlanguage = {en},\n\turldate = {2023-05-09},\n\tjournal = {International Journal of Infectious Diseases},\n\tauthor = {Zannoli, Silvia and Brandolini, Martina and Marino, Maria Michela and Denicolò, Agnese and Mancini, Andrea and Taddei, Francesca and Arfilli, Valentina and Manera, Martina and Gatti, Giulia and Battisti, Arianna and Grumiro, Laura and Scalcione, Agata and Dirani, Giorgio and Sambri, Vittorio},\n\tmonth = mar,\n\tyear = {2023},\n\tkeywords = {DDM v4, Recombinant XS, SARS-CoV-2 variants, Whole genome sequencing},\n\tpages = {65--70},\n}\n\n

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\n \n\n \n \n \n \n \n \n Immunotherapy in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma: biological landscape and prognostic biomarkers to improve patients' stratification.\n \n \n \n \n\n\n \n Serafini, M. S.\n\n\n \n\n\n\n . March 2023.\n Publisher: The Open University\n\n\n\n
\n\n\n\n \n \n $\"Immunotherapy$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{serafini_mara_serena_immunotherapy_2023,\n\ttitle = {Immunotherapy in {Recurrent}/{Metastatic} {Head} and {Neck} {Squamous} {Cell} {Carcinoma}: biological landscape and prognostic biomarkers to improve patients' stratification},\n\tcopyright = {Creative Commons Attribution Non Commercial No Derivatives 4.0 International, Creative Commons Attribution Non Commercial No Derivatives 4.0 International, Creative Commons Attribution Non Commercial No Derivatives 4.0 International},\n\tshorttitle = {Immunotherapy in {Recurrent}/{Metastatic} {Head} and {Neck} {Squamous} {Cell} {Carcinoma}},\n\turl = {https://oro.open.ac.uk/id/eprint/87525},\n\tdoi = {10.21954/OU.RO.000155E5},\n\tabstract = {Head and neck squamous cell carcinoma (HNSCC) is the eight most frequent cancer in the world, and approximately 2/3 of the patients are diagnosed at locally advanced stages (stage III or IV). Despite improvements in HNSCC management and the aggressiveness of first-line curative treatment, 65\\% of treated patients experience local recurrence or distant metastasis. Moreover, patients diagnosed with recurrence or distant metastasis have a poor prognosis (from 6 to 12 months) and 5-years survival less than 50\\%. From 2016 the clinical practice was revolutionized by the introduction of immuno-checkpoint inhibitors, approved for the treatment of recurrent/metastatic HNSCC patients. Nevertheless, only a small subset of patients respond to this therapy and currently predictive biomarkers are still under investigation. Herein, we investigated the tumor biology of R/M HNSCC patients, platinum-refractory, enrolled in the phase IIIb clinical trial Nivactor (EudraCT Number: 2017-000562-30), in which patients were treated with nivolumab. Across the study of single biomarkers and the extensive profiling through genomic and transcriptomic analyses, we aimed to characterize the tumor molecular peculiarity of patients that experienced response or those with the longer survival. While the prognostic/predictive role of Programmed Cell Death Ligand-1 (PD-L1; studied by IHC), Tumor mutational burden (TMB) and microsatellite instability (MSI) appeared to be relatively limited for R/M HNSCC patients, 8 expression signatures (retrieved from literature) showed up significant association with survival and contributed to highlight and extricate the extreme complexity of the tumor microenvironment of HNSCC, which appeared to be strongly immunosuppressive (suggesting and corroborating the activation of several mechanisms of immune evasion). Nevertheless, the testing of previously identified six HNSCC subtypes (\\textit{De Cecco et al.}) with specific biological and prognostic characteristics, indicated for two of them a strong prognostic role and a significant correlation with response. In conclusion, the current study demonstrated the strong relevance of gene expression signatures in HNSCC context (over the mere study of somatic mutations) to identify the biological features associated with benefits from immunotherapy. However, additional analyses for the validation of their significance are required.},\n\tlanguage = {en},\n\turldate = {2023-05-09},\n\tauthor = {Serafini, Mara Serena},\n\tmonth = mar,\n\tyear = {2023},\n\tnote = {Publisher: The Open University},\n\tkeywords = {DDM, DDM for TSO500, TSO500},\n}\n\n

\n\n\n

\n Head and neck squamous cell carcinoma (HNSCC) is the eight most frequent cancer in the world, and approximately 2/3 of the patients are diagnosed at locally advanced stages (stage III or IV). Despite improvements in HNSCC management and the aggressiveness of first-line curative treatment, 65% of treated patients experience local recurrence or distant metastasis. Moreover, patients diagnosed with recurrence or distant metastasis have a poor prognosis (from 6 to 12 months) and 5-years survival less than 50%. From 2016 the clinical practice was revolutionized by the introduction of immuno-checkpoint inhibitors, approved for the treatment of recurrent/metastatic HNSCC patients. Nevertheless, only a small subset of patients respond to this therapy and currently predictive biomarkers are still under investigation. Herein, we investigated the tumor biology of R/M HNSCC patients, platinum-refractory, enrolled in the phase IIIb clinical trial Nivactor (EudraCT Number: 2017-000562-30), in which patients were treated with nivolumab. Across the study of single biomarkers and the extensive profiling through genomic and transcriptomic analyses, we aimed to characterize the tumor molecular peculiarity of patients that experienced response or those with the longer survival. While the prognostic/predictive role of Programmed Cell Death Ligand-1 (PD-L1; studied by IHC), Tumor mutational burden (TMB) and microsatellite instability (MSI) appeared to be relatively limited for R/M HNSCC patients, 8 expression signatures (retrieved from literature) showed up significant association with survival and contributed to highlight and extricate the extreme complexity of the tumor microenvironment of HNSCC, which appeared to be strongly immunosuppressive (suggesting and corroborating the activation of several mechanisms of immune evasion). Nevertheless, the testing of previously identified six HNSCC subtypes (De Cecco et al.) with specific biological and prognostic characteristics, indicated for two of them a strong prognostic role and a significant correlation with response. In conclusion, the current study demonstrated the strong relevance of gene expression signatures in HNSCC context (over the mere study of somatic mutations) to identify the biological features associated with benefits from immunotherapy. However, additional analyses for the validation of their significance are required.\n

\n\n\n

\n \n\n \n \n \n \n \n \n First Reported Case of Malignant Ectomesenchymoma with p.Leu122Arg Mutation in MYOD1 Gene: Extensive Intra- and Extracranial Tumor in a 15-Year-Old Female.\n \n \n \n \n\n\n \n Pena-Burgos, E. M.; De Sabando, D. P.; Utrilla, C.; Pozo-Kreilinger, J. J.; Sastre, A.; Rubio, P.; Escudero, A.; Mendiola-Sabio, M.; and Pérez-Martínez, A.\n\n\n \n\n\n\n Head and Neck Pathology. March 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"First$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{pena-burgos_first_2023,\n\ttitle = {First {Reported} {Case} of {Malignant} {Ectomesenchymoma} with p.{Leu122Arg} {Mutation} in {MYOD1} {Gene}: {Extensive} {Intra}- and {Extracranial} {Tumor} in a 15-{Year}-{Old} {Female}},\n\tissn = {1936-0568},\n\tshorttitle = {First {Reported} {Case} of {Malignant} {Ectomesenchymoma} with p.{Leu122Arg} {Mutation} in {MYOD1} {Gene}},\n\turl = {https://doi.org/10.1007/s12105-023-01542-0},\n\tdoi = {10.1007/s12105-023-01542-0},\n\tabstract = {Ectomesenchymomas (EMs) are extremely rare neoplasms composed of malignant mesenchymal components and neuroectodermal derivatives. They are described in a wide variety of locations, with the head and neck region being one of the most frequently involved areas. EMs are usually managed as high-risk rhabdomyosarcomas and have similar outcomes.},\n\tlanguage = {en},\n\turldate = {2023-05-09},\n\tjournal = {Head and Neck Pathology},\n\tauthor = {Pena-Burgos, E. M. and De Sabando, D. Plaza-López and Utrilla, C. and Pozo-Kreilinger, J. J. and Sastre, A. and Rubio, P. and Escudero, A. and Mendiola-Sabio, M. and Pérez-Martínez, A.},\n\tmonth = mar,\n\tyear = {2023},\n\tkeywords = {Custom STS, DDM, MYOD1, STS},\n}\n\n

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\n \n\n \n \n \n \n \n Molecular Genetics of Myeloid Malignancies Drives Modern Treatment Options.\n \n \n \n\n\n \n Silvia, S.\n\n\n \n\n\n\n . March 2023.\n \n\n\n\n
\n\n\n\n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{silvia_molecular_2023,\n\ttitle = {Molecular {Genetics} of {Myeloid} {Malignancies} {Drives} {Modern} {Treatment} {Options}},\n\tlanguage = {en},\n\tauthor = {Silvia, Salmoiraghi},\n\tmonth = mar,\n\tyear = {2023},\n\tkeywords = {DDM, MYS},\n}\n\n

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\n \n\n \n \n \n \n \n \n Novel, homozygous RAB3GAP1 c.2606 + 1G\\textgreaterA, p.Glu830ValfsTer9 variant and chromosome 3q29 duplication in a Turkish individual with Warburg micro syndrome.\n \n \n \n \n\n\n \n Geckinli, B.; Turkyilmaz, A.; Alavanda, C.; Sager, G.; Arslan Ates, E.; Soylemez, M. A.; and Arman, A.\n\n\n \n\n\n\n Clinical Dysmorphology, 32(2): 55. March 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Novel,$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{geckinli_novel_2023,\n\ttitle = {Novel, homozygous {RAB3GAP1} c.2606 + {1G}{\\textgreater}{A}, p.{Glu830ValfsTer9} variant and chromosome 3q29 duplication in a {Turkish} individual with {Warburg} micro syndrome},\n\tvolume = {32},\n\tissn = {0962-8827},\n\turl = {https://journals.lww.com/clindysmorphol/Abstract/2023/04000/Novel,_homozygous_RAB3GAP1_c_2606___1G_A,.2.aspx},\n\tdoi = {10.1097/MCD.0000000000000454},\n\tabstract = {Warburg micro syndrome (WARBM) is a rare, autosomal recessive, neurodevelopmental disorder characterized by microcephaly, cortical dysplasia, corpus callosum hypoplasia, congenital hypotonia leading to subsequent spastic quadriplegia, severe developmental delay and hypogenitalism. Ophthalmologic findings that may affect any ocular segment including characteristic, small, atonic pupils. WARBM is known to be caused by biallelic, pathogenic variants in at least five genes although additional genetic loci may exist. The RAB3GAP1 c.748 + 1G{\\textgreater}A, p.Asp250CysfsTer24 founder variant has been described in families of Turkish ancestry. We report the clinical and molecular findings in three, unrelated, Turkish families with WARBM. A novel c.974−2A{\\textgreater}G variant causing WARBM in three siblings of Turkish descent was found. Functional studies of the novel, c.2606 + 1G{\\textgreater}A variant in patients’ mRNA revealed skipping of exon 22 which results in a premature stop codon in exon 23. However, the clinical consequences of this variant are blended given that the individual also had a maternally inherited chromosome 3q29 microduplication.},\n\tlanguage = {en-US},\n\tnumber = {2},\n\turldate = {2023-05-09},\n\tjournal = {Clinical Dysmorphology},\n\tauthor = {Geckinli, Bilge and Turkyilmaz, Ayberk and Alavanda, Ceren and Sager, Gunes and Arslan Ates, Esra and Soylemez, Mehmet Ali and Arman, Ahmet},\n\tmonth = mar,\n\tyear = {2023},\n\tpages = {55},\n}\n\n

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\n \n\n \n \n \n \n \n \n Efficient correction of ABCA4 variants by CRISPR-Cas9 in hiPSCs derived from Stargardt disease patients.\n \n \n \n \n\n\n \n Siles, L.; Ruiz-Nogales, S.; Navinés-Ferrer, A.; Méndez-Vendrell, P.; and Pomares, E.\n\n\n \n\n\n\n Molecular Therapy - Nucleic Acids, 32: 64–79. March 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Efficient$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{siles_efficient_2023,\n\ttitle = {Efficient correction of {ABCA4} variants by {CRISPR}-{Cas9} in {hiPSCs} derived from {Stargardt} disease patients},\n\tvolume = {32},\n\tissn = {21622531},\n\turl = {https://linkinghub.elsevier.com/retrieve/pii/S2162253123000525},\n\tdoi = {10.1016/j.omtn.2023.02.032},\n\tlanguage = {en},\n\turldate = {2023-05-09},\n\tjournal = {Molecular Therapy - Nucleic Acids},\n\tauthor = {Siles, Laura and Ruiz-Nogales, Sheila and Navinés-Ferrer, Arnau and Méndez-Vendrell, Pilar and Pomares, Esther},\n\tmonth = mar,\n\tyear = {2023},\n\tkeywords = {Alamut v.1.4.},\n\tpages = {64--79},\n}\n\n

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\n \n\n \n \n \n \n \n \n Paired Comparison of Routine Molecular Screening of Patient Samples with Advanced Non-Small Cell Lung Cancer in Circulating Cell-Free DNA Using Three Targeted Assays.\n \n \n \n \n\n\n \n Barthelemy, D.; Lescuyer, G.; Geiguer, F.; Grolleau, E.; Gauthier, A.; Balandier, J.; Raffin, M.; Bardel, C.; Bouyssounouse, B.; Rodriguez-Lafrasse, C.; Couraud, S.; Wozny, A.; and Payen, L.\n\n\n \n\n\n\n Cancers, 15(5): 1574. March 2023.\n Number: 5 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Paired$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{barthelemy_paired_2023,\n\ttitle = {Paired {Comparison} of {Routine} {Molecular} {Screening} of {Patient} {Samples} with {Advanced} {Non}-{Small} {Cell} {Lung} {Cancer} in {Circulating} {Cell}-{Free} {DNA} {Using} {Three} {Targeted} {Assays}},\n\tvolume = {15},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2072-6694},\n\turl = {https://www.mdpi.com/2072-6694/15/5/1574},\n\tdoi = {10.3390/cancers15051574},\n\tabstract = {Introduction: Progressive advanced non-small cell lung cancer (NSCLC) accounts for about 80–85\\% of all lung cancers. Approximately 10–50\\% of patients with NSCLC harbor targetable activating mutations, such as in-frame deletions in Exon 19 (Ex19del) of EGFR. Currently, for patients with advanced NSCLC, testing for sensitizing mutations in EGFR is mandatory prior to the administration of tyrosine kinase inhibitors. Patients and Methods: Plasma was collected from patients with NSCLC. We carried out targeted NGS using the Plasma-SeqSensei™ SOLID CANCER IVD kit on cfDNA (circulating free DNA). Clinical concordance for plasma detection of known oncogenic drivers was reported. In a subset of cases, validation was carried out using an orthogonal OncoBEAMTM EGFR V2 assay, as well as with our custom validated NGS assay. Somatic alterations were filtered, removing somatic mutations attributable to clonal hematopoiesis for our custom validated NGS assay. Results: In the plasma samples, driver targetable mutations were studied, with a mutant allele frequency (MAF) ranging from 0.00\\% (negative detection) to 82.25\\%, using the targeted next-generation sequencing Plasma-SeqSensei™ SOLID CANCER IVD Kit. In comparison with the OncoBEAMTM EGFR V2 kit, the EGFR concordance is 89.16\\% (based on the common genomic regions). The sensitivity and specificity rates based on the genomic regions (EGFR exons 18, 19, 20, and 21) were 84.62\\% and 94.67\\%. Furthermore, the observed clinical genomic discordances were present in 25\\% of the samples: 5\\% in those linked to the lower of coverage of the OncoBEAMTM EGFR V2 kit, 7\\% in those induced by the sensitivity limit on the EGFR with the Plasma-SeqSensei™ SOLID CANCER IVD Kit, and 13\\% in the samples linked to the larger KRAS, PIK3CA, BRAF coverage of the Plasma-SeqSensei™ SOLID CANCER IVD kit. Most of these somatic alterations were cross validated in our orthogonal custom validated NGS assay, used in the routine management of patients. The concordance is 82.19\\% in the common genomic regions (EGFR exons 18, 19, 20, 21; KRAS exons 2, 3, 4; BRAF exons 11, 15; and PIK3CA exons 10, 21). The sensitivity and specificity rates were 89.38\\% and 76.12\\%, respectively. The 32\\% of genomic discordances were composed of 5\\% caused by the limit of coverage of the Plasma-SeqSensei™ SOLID CANCER IVD kit, 11\\% induced by the sensitivity limit of our custom validated NGS assay, and 16\\% linked to the additional oncodriver analysis, which is only covered by our custom validated NGS assay. Conclusions: The Plasma-SeqSensei™ SOLID CANCER IVD kit resulted in de novo detection of targetable oncogenic drivers and resistance alterations, with a high sensitivity and accuracy for low and high cfDNA inputs. Thus, this assay is a sensitive, robust, and accurate test.},\n\tlanguage = {en},\n\tnumber = {5},\n\turldate = {2023-05-09},\n\tjournal = {Cancers},\n\tauthor = {Barthelemy, David and Lescuyer, Gaelle and Geiguer, Florence and Grolleau, Emmanuel and Gauthier, Arnaud and Balandier, Julie and Raffin, Margaux and Bardel, Claire and Bouyssounouse, Bruno and Rodriguez-Lafrasse, Claire and Couraud, Sébastien and Wozny, Anne-Sophie and Payen, Léa},\n\tmonth = mar,\n\tyear = {2023},\n\tnote = {Number: 5\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Custom Panel, DDM, cfDNA, custom validated NGS assay, lung cancer},\n\tpages = {1574},\n}\n\n

\n\n\n

\n Introduction: Progressive advanced non-small cell lung cancer (NSCLC) accounts for about 80–85% of all lung cancers. Approximately 10–50% of patients with NSCLC harbor targetable activating mutations, such as in-frame deletions in Exon 19 (Ex19del) of EGFR. Currently, for patients with advanced NSCLC, testing for sensitizing mutations in EGFR is mandatory prior to the administration of tyrosine kinase inhibitors. Patients and Methods: Plasma was collected from patients with NSCLC. We carried out targeted NGS using the Plasma-SeqSensei™ SOLID CANCER IVD kit on cfDNA (circulating free DNA). Clinical concordance for plasma detection of known oncogenic drivers was reported. In a subset of cases, validation was carried out using an orthogonal OncoBEAMTM EGFR V2 assay, as well as with our custom validated NGS assay. Somatic alterations were filtered, removing somatic mutations attributable to clonal hematopoiesis for our custom validated NGS assay. Results: In the plasma samples, driver targetable mutations were studied, with a mutant allele frequency (MAF) ranging from 0.00% (negative detection) to 82.25%, using the targeted next-generation sequencing Plasma-SeqSensei™ SOLID CANCER IVD Kit. In comparison with the OncoBEAMTM EGFR V2 kit, the EGFR concordance is 89.16% (based on the common genomic regions). The sensitivity and specificity rates based on the genomic regions (EGFR exons 18, 19, 20, and 21) were 84.62% and 94.67%. Furthermore, the observed clinical genomic discordances were present in 25% of the samples: 5% in those linked to the lower of coverage of the OncoBEAMTM EGFR V2 kit, 7% in those induced by the sensitivity limit on the EGFR with the Plasma-SeqSensei™ SOLID CANCER IVD Kit, and 13% in the samples linked to the larger KRAS, PIK3CA, BRAF coverage of the Plasma-SeqSensei™ SOLID CANCER IVD kit. Most of these somatic alterations were cross validated in our orthogonal custom validated NGS assay, used in the routine management of patients. The concordance is 82.19% in the common genomic regions (EGFR exons 18, 19, 20, 21; KRAS exons 2, 3, 4; BRAF exons 11, 15; and PIK3CA exons 10, 21). The sensitivity and specificity rates were 89.38% and 76.12%, respectively. The 32% of genomic discordances were composed of 5% caused by the limit of coverage of the Plasma-SeqSensei™ SOLID CANCER IVD kit, 11% induced by the sensitivity limit of our custom validated NGS assay, and 16% linked to the additional oncodriver analysis, which is only covered by our custom validated NGS assay. Conclusions: The Plasma-SeqSensei™ SOLID CANCER IVD kit resulted in de novo detection of targetable oncogenic drivers and resistance alterations, with a high sensitivity and accuracy for low and high cfDNA inputs. Thus, this assay is a sensitive, robust, and accurate test.\n

\n\n\n

\n \n\n \n \n \n \n \n \n Performance Characteristics of Oncomine Focus Assay for Theranostic Analysis of Solid Tumors, A (21-Months) Real-Life Study.\n \n \n \n \n\n\n \n Bamba-Funck, J.; Fabre, E. E.; Kambouchner, M.; and Schischmanoff, O.\n\n\n \n\n\n\n Diagnostics, 13(5): 937. March 2023.\n Number: 5 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Performance$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{bamba-funck_performance_2023,\n\ttitle = {Performance {Characteristics} of {Oncomine} {Focus} {Assay} for {Theranostic} {Analysis} of {Solid} {Tumors}, {A} (21-{Months}) {Real}-{Life} {Study}},\n\tvolume = {13},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2075-4418},\n\turl = {https://www.mdpi.com/2075-4418/13/5/937},\n\tdoi = {10.3390/diagnostics13050937},\n\tabstract = {Next generation sequencing analysis is crucial for therapeutic decision in various solid tumor contexts. The sequencing method must remain accurate and robust throughout the instrument lifespan allowing the biological validation of patients’ results. This study aims to evaluate the long-term sequencing performances of the Oncomine Focus assay kit allowing theranostic DNA and RNA variants detection on the Ion S5XL instrument. We evaluated the sequencing performances of 73 consecutive chips over a 21-month period and detailed the sequencing data obtained from both quality controls and clinical samples. The metrics describing sequencing quality remained stable throughout the study. We showed that an average of 11 × 106 (±0.3 × 106) reads were obtained using a 520 chip leading to an average of 6.0 × 105 (±2.6 × 105) mapped reads per sample. Of 400 consecutive samples, 95.8 ± 16\\% of amplicons reached the depth threshold of 500X. Slight modifications of the bioinformatics workflow improved DNA analytical sensitivity and allowed the systematic detection of expected SNV, indel, CNV, and RNA alterations in quality controls samples. The low inter-run variability of DNA and RNA—even at low variant allelic fraction, amplification factor, or reads counts—indicated that our method was adapted to clinical practice. The analysis of 429 clinical DNA samples indicated that the modified bioinformatics workflow allowed detection of 353 DNA variants and 88 gene amplifications. RNA analysis of 55 clinical samples revealed 7 alterations. This is the first study showing the long-term robustness of the Oncomine Focus assay in clinical routine practice.},\n\tlanguage = {en},\n\tnumber = {5},\n\turldate = {2023-05-09},\n\tjournal = {Diagnostics},\n\tauthor = {Bamba-Funck, Jessica and Fabre, Emmanuelle E. and Kambouchner, Marianne and Schischmanoff, Olivier},\n\tmonth = mar,\n\tyear = {2023},\n\tnote = {Number: 5\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {SGPL, copy number variation (CNV), next generation sequencing (NGS), single nucleotide variation (SNV), solid tumors},\n\tpages = {937},\n}\n\n

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\n \n\n \n \n \n \n \n \n A Novel Homozygous Mutation of AIRE Gene in a Patient With Autoimmune Polyglandular Syndrome Type I.\n \n \n \n \n\n\n \n Tautiva-Rojas, C. M; Bogarin-Solano, R.; Santamaría-Quesada, C.; and Pacheco-Muñoz, M.\n\n\n \n\n\n\n Cureus. February 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{tautiva-rojas_novel_2023,\n\ttitle = {A {Novel} {Homozygous} {Mutation} of {AIRE} {Gene} in a {Patient} {With} {Autoimmune} {Polyglandular} {Syndrome} {Type} {I}},\n\tissn = {2168-8184},\n\turl = {https://www.cureus.com/articles/140921-a-novel-homozygous-mutation-of-aire-gene-in-a-patient-with-autoimmune-polyglandular-syndrome-type-i},\n\tdoi = {10.7759/cureus.35374},\n\tabstract = {Autoimmune polyglandular syndrome type I (APS1) shows common features such as mucocutaneous candidiasis, hypoparathyroidism, and hypoadrenalism. The clinical manifestations and their onset are highly variable. Besides endocrine abnormalities, patients can present with dental problems, keratoconjunctivitis, fever, rash, chronic diarrhea, and autoimmune hepatitis. We discuss the case of a 5year-old female who presented initially with a new-onset seizure due to severe hypocalcemia and was diagnosed with primary hypoparathyroidism. Because she also had a history of chronic mucocutaneous candidiasis, chronic diarrhea, and the presence of autoantibodies tested positive, the diagnosis of APS1 was suspected. Genetic testing detected a novel pathogenic homozygous AIRE mutation, which confirmed the diagnosis. She began multidisciplinary treatment with antifungals, calcium supplements, and parathyroid hormone analogs.},\n\tlanguage = {en},\n\turldate = {2023-03-09},\n\tjournal = {Cureus},\n\tauthor = {Tautiva-Rojas, Camila M and Bogarin-Solano, Roberto and Santamaría-Quesada, Carlos and Pacheco-Muñoz, Mariana},\n\tmonth = feb,\n\tyear = {2023},\n\tkeywords = {CES v2, DDM},\n}\n\n

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\n \n\n \n \n \n \n \n \n Evolving Risk Classifications in AML in a Real-Life Scenario: After Changes upon Changes, Is It More and More Adverse?.\n \n \n \n \n\n\n \n Aparicio-Pérez, C.; Prados de la Torre, E.; Sanchez-Garcia, J.; Martín-Calvo, C.; Martínez-Losada, C.; Casaño-Sanchez, J.; Serrano-López, J.; and Serrano, J.\n\n\n \n\n\n\n Cancers, 15(5): 1425. February 2023.\n Number: 5 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Evolving$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{aparicio-perez_evolving_2023,\n\ttitle = {Evolving {Risk} {Classifications} in {AML} in a {Real}-{Life} {Scenario}: {After} {Changes} upon {Changes}, {Is} {It} {More} and {More} {Adverse}?},\n\tvolume = {15},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2072-6694},\n\tshorttitle = {Evolving {Risk} {Classifications} in {AML} in a {Real}-{Life} {Scenario}},\n\turl = {https://www.mdpi.com/2072-6694/15/5/1425},\n\tdoi = {10.3390/cancers15051425},\n\tabstract = {Acute myeloid leukemia (AML) is a heterogeneous disease classified into three risk categories (favorable, intermediate and adverse) with significant differences in outcomes. Definitions of risk categories evolve overtime, incorporating advances in molecular knowledge of AML. In this study, we analyzed the impacts of evolving risk classifications in 130 consecutive AML patients in a single-center real-life experience. Complete cytogenetic and molecular data were collected using conventional qPCR and targeted Next Generation Sequencing (NGS). Five-year OS probabilities were consistent among all classification models (roughly 50–72\\%, 26–32\\% and 16–20\\% for favorable, intermediate and adverse risk groups, respectively). In the same way, the medians of survival months and prediction power were similar in all models. In each update, around 20\\% of patients were re-classified. The adverse category consistently increased over time (31\\% in MRC, 34\\% in ELN2010, 50\\% in ELN2017), reaching up to 56\\% in the recent ELN2022. Noteworthily, in multivariate models, only age and the presence of TP53 mutations remained statistically significant. With updates in risk-classification models, the percentage of patients assigned to the adverse group is increasing, and so will the indications for allogeneic stem cell transplantation.},\n\tlanguage = {en},\n\tnumber = {5},\n\turldate = {2023-03-09},\n\tjournal = {Cancers},\n\tauthor = {Aparicio-Pérez, Clara and Prados de la Torre, Esther and Sanchez-Garcia, Joaquin and Martín-Calvo, Carmen and Martínez-Losada, Carmen and Casaño-Sanchez, Javier and Serrano-López, Juana and Serrano, Josefina},\n\tmonth = feb,\n\tyear = {2023},\n\tnote = {Number: 5\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Acute myeloid leukemia, MYS, Myeloid Solution, Myeloid Solution Panel},\n\tpages = {1425},\n}\n\n

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\n \n\n \n \n \n \n \n \n Functional Assays Combined with Pre-mRNA-Splicing Analysis Improve Variant Classification and Diagnostics for Individuals with Neurofibromatosis Type 1 and Legius Syndrome.\n \n \n \n \n\n\n \n Douben, H.; Hoogeveen-Westerveld, M.; Nellist, M.; Louwen, J.; Haan, M. K.; Punt, M.; van Ommeren, B.; van Unen, L.; Elfferich, P.; Kasteleijn, E.; van Bever, Y.; van Vliet, M.; Oostenbrink, R.; Saris, J. J.; Wagner, A.; van Ierland, Y.; van Ham, T.; and van Minkelen, R.\n\n\n \n\n\n\n Human Mutation, 2023: e9628049. February 2023.\n Publisher: Hindawi\n\n\n\n
\n\n\n\n \n \n $\"Functional$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{douben_functional_2023,\n\ttitle = {Functional {Assays} {Combined} with {Pre}-{mRNA}-{Splicing} {Analysis} {Improve} {Variant} {Classification} and {Diagnostics} for {Individuals} with {Neurofibromatosis} {Type} 1 and {Legius} {Syndrome}},\n\tvolume = {2023},\n\turl = {https://www.hindawi.com/journals/humu/2023/9628049/},\n\tdoi = {10.1155/2023/9628049},\n\tabstract = {Neurofibromatosis type 1 (NF1) and Legius syndrome (LS) are caused by inactivating variants in NF1 and SPRED1. NF1 encodes neurofibromin (NF), a GTPase-activating protein (GAP) for RAS that interacts with the SPRED1 product, Sprouty-related protein with an EVH (Ena/Vasp homology) domain 1 (SPRED1). Obtaining a clinical and molecular diagnosis of NF1 or LS can be challenging due to the phenotypic diversity, the size and complexity of the NF1 and SPRED1 loci, and uncertainty over the effects of some NF1 and SPRED1 variants on pre-mRNA splicing and/or protein expression and function. To improve NF1 and SPRED1 variant classification and establish pathogenicity for NF1 and SPRED1 variants identified in individuals with NF1 or LS, we analyzed patient RNA by RT-PCR and performed in vitro exon trap experiments and estimated NF and SPRED1 protein expression, RAS GAP activity, and interaction. We obtained evidence to support pathogenicity according to American College of Medical Genetics guidelines for 73/114 variants tested, demonstrating the utility of functional approaches for NF1 and SPRED1 variant classification and NF and LS diagnostics.},\n\tlanguage = {en},\n\turldate = {2023-03-09},\n\tjournal = {Human Mutation},\n\tauthor = {Douben, Hannie and Hoogeveen-Westerveld, Marianne and Nellist, Mark and Louwen, Jesse and Haan, Marian Kroos-de and Punt, Mattijs and van Ommeren, Babeth and van Unen, Leontine and Elfferich, Peter and Kasteleijn, Esmee and van Bever, Yolande and van Vliet, Margreethe and Oostenbrink, Rianne and Saris, Jasper J. and Wagner, Anja and van Ierland, Yvette and van Ham, Tjakko and van Minkelen, Rick},\n\tmonth = feb,\n\tyear = {2023},\n\tnote = {Publisher: Hindawi},\n\tkeywords = {Alamut, Alamut Visual Plus v.1.5.1},\n\tpages = {e9628049},\n}\n\n

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\n \n\n \n \n \n \n \n \n Prognostic and Predictive Biomarkers in Familial Breast Cancer.\n \n \n \n \n\n\n \n Deb, S.; Chakrabarti, A.; and Fox, S. B.\n\n\n \n\n\n\n Cancers, 15(4): 1346. February 2023.\n Number: 4 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Prognostic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{deb_prognostic_2023,\n\ttitle = {Prognostic and {Predictive} {Biomarkers} in {Familial} {Breast} {Cancer}},\n\tvolume = {15},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2072-6694},\n\turl = {https://www.mdpi.com/2072-6694/15/4/1346},\n\tdoi = {10.3390/cancers15041346},\n\tabstract = {Large numbers of breast cancers arise within a familial context, either with known inherited germline mutations largely within DNA repair genes, or with a strong family history of breast and/or ovarian cancer, with unknown genetic underlying mechanisms. These cancers appear to be different to sporadic cases, with earlier age of onset, increased multifocality and with association with specific breast cancer histological and phenotypic subtypes. Furthermore, tumours showing homologous recombination deficiency, due to loss of BRCA1, BRCA2, PALB2 and CHEK2 function, have been shown to be especially sensitive to platinum-based chemotherapeutics and PARP inhibition. While there is extensive research and data accrued on risk stratification and genetic predisposition, there are few data pertaining to relevant prognostic and predictive biomarkers within this breast cancer subgroup. The following is a review of such biomarkers in male and female familial breast cancer, although the data for the former are particularly sparse.},\n\tlanguage = {en},\n\tnumber = {4},\n\turldate = {2023-03-09},\n\tjournal = {Cancers},\n\tauthor = {Deb, Siddhartha and Chakrabarti, Anannya and Fox, Stephen B.},\n\tmonth = feb,\n\tyear = {2023},\n\tnote = {Number: 4\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {BRCA1, BRCA1/2, BRCA2, DDM, HRD},\n\tpages = {1346},\n}\n\n

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\n \n\n \n \n \n \n \n \n High-Efficiency CRISPR/Cas9-Mediated Correction of a Homozygous Mutation in Achromatopsia-Patient-Derived iPSCs.\n \n \n \n \n\n\n \n Siles, L.; Gaudó, P.; and Pomares, E.\n\n\n \n\n\n\n International Journal of Molecular Sciences, 24(4): 3655. February 2023.\n Number: 4 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"High-Efficiency$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{siles_high-efficiency_2023,\n\ttitle = {High-{Efficiency} {CRISPR}/{Cas9}-{Mediated} {Correction} of a {Homozygous} {Mutation} in {Achromatopsia}-{Patient}-{Derived} {iPSCs}},\n\tvolume = {24},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {1422-0067},\n\turl = {https://www.mdpi.com/1422-0067/24/4/3655},\n\tdoi = {10.3390/ijms24043655},\n\tabstract = {Achromatopsia is an autosomal recessive disorder, in which cone photoreceptors undergo progressive degeneration, causing color blindness and poor visual acuity, among other significant eye affectations. It belongs to a group of inherited retinal dystrophies that currently have no treatment. Although functional improvements have been reported in several ongoing gene therapy studies, more efforts and research should be carried out to enhance their clinical application. In recent years, genome editing has arisen as one of the most promising tools for personalized medicine. In this study, we aimed to correct a homozygous PDE6C pathogenic variant in hiPSCs derived from a patient affected by achromatopsia through CRISPR/Cas9 and TALENs technologies. Here, we demonstrate high efficiency in gene editing by CRISPR/Cas9 but not with TALENs approximation. Despite a few of the edited clones displaying heterozygous on-target defects, the proportion of corrected clones with a potentially restored wild-type PDE6C protein was more than half of the total clones analyzed. In addition, none of them presented off-target aberrations. These results significantly contribute to advances in single-nucleotide gene editing and the development of future strategies for the treatment of achromatopsia.},\n\tlanguage = {en},\n\tnumber = {4},\n\turldate = {2023-03-09},\n\tjournal = {International Journal of Molecular Sciences},\n\tauthor = {Siles, Laura and Gaudó, Paula and Pomares, Esther},\n\tmonth = feb,\n\tyear = {2023},\n\tnote = {Number: 4\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Alamut, Alamut Batch 1.4.0, Alamut v1.4, CRISPR/Cas9},\n\tpages = {3655},\n}\n\n

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\n \n\n \n \n \n \n \n \n Clinical Features and Genomic Landscape of Myeloproliferative Neoplasm (MPN) Patients with Autoimmune and Inflammatory Diseases (AID).\n \n \n \n \n\n\n \n Elessa, D.; Zhao, L.; de Oliveira, R. D.; Maslah, N.; Soret, J.; Verger, E.; Marcault, C.; Parquet, N.; Fenaux, P.; Adès, L.; Raffoux, E.; Giraudier, S.; Fain, O.; Cassinat, B.; Kiladjian, J.; Mekinian, A.; and Benajiba, L.\n\n\n \n\n\n\n Technical Report In Review, February 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Clinical$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@techreport{elessa_clinical_2023,\n\ttype = {preprint},\n\ttitle = {Clinical {Features} and {Genomic} {Landscape} of {Myeloproliferative} {Neoplasm} ({MPN}) {Patients} with {Autoimmune} and {Inflammatory} {Diseases} ({AID})},\n\turl = {https://www.researchsquare.com/article/rs-2526712/v1},\n\tabstract = {Abstract\n          \n            There are few data regarding the association of autoimmune and inflammatory diseases (AID) with Philadelphia negative myeloproliferative neoplasms (MPN). In this retrospective study, we describe the prevalence, clinical and biological features and outcome of AID association in MPN.\nA total of 1541 MPN patients were included, encompassing 95 (6\\%) patients with AID. Female patients were predominant within the AID group (65\\% versus 54\\%, p=0.03). A total of 103 AID diagnoses were reported in 95 patients, including 48 organ-specific AID, 13 inflammatory arthritis, 9 connective tissue diseases, 9 dermatosis, 6 systemic vasculitis and 18 unclassified AID. The prevalence of\n            TET2\n            mutations was higher in the AID cohort (32\\% versus 22\\%), although not statistically significant (p=0.08). In subgroup analysis of patients with myelofibrosis,\n            TET2\n            mutations were more prevalent in AID group (p=0.025). The prevalence of driver and other additional mutations did not differ between the 2 groups. The association with AID did not impact overall survival (p=0.67), transformation-free survival (p=0.37) or secondary myelofibrosis-free survival (p=0.91).\nOur data suggest that the prevalence of AID is similar in MPN patients to that of the general population.\n            TET2\n            mutations are highly prevalent in MPN patients with AID potentially suggesting a shared physiopathology.},\n\tlanguage = {en},\n\turldate = {2023-03-09},\n\tinstitution = {In Review},\n\tauthor = {Elessa, Dikelele and Zhao, Lin-Pierre and de Oliveira, Rafael Daltro and Maslah, Nabih and Soret, Juliette and Verger, Emmanuelle and Marcault, Clémence and Parquet, Nathalie and Fenaux, Pierre and Adès, Lionel and Raffoux, Emmanuel and Giraudier, Stéphane and Fain, Olivier and Cassinat, Bruno and Kiladjian, Jean-Jacques and Mekinian, Arsène and Benajiba, Lina},\n\tmonth = feb,\n\tyear = {2023},\n\tdoi = {10.21203/rs.3.rs-2526712/v1},\n\tkeywords = {Custom MYS, DDM, MYS},\n}\n\n

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\n \n\n \n \n \n \n \n \n Treatment of STING-associated vasculopathy with onset in infancy in patients carrying a novel mutation in the TMEM173 gene with the JAK3-inhibitor tofacitinib.\n \n \n \n \n\n\n \n Elvan Tokgun, P.; Karagenc, N.; Karasu, U.; Tokgun, O.; Turel, S.; Demiray, A.; Akca, H.; and Yüksel, S.\n\n\n \n\n\n\n Archives of Rheumatology,1443. February 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Treatment$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{elvan_tokgun_treatment_2023,\n\ttitle = {Treatment of {STING}-associated vasculopathy with onset in infancy in patients carrying a novel mutation in the {TMEM173} gene with the {JAK3}-inhibitor tofacitinib},\n\tissn = {2148-5046, 2618-6500},\n\turl = {https://archivesofrheumatology.org/doi/10.46497/ArchRheumatol.2023.9927},\n\tdoi = {10.46497/ArchRheumatol.2023.9927},\n\tabstract = {Objectives:\n              This study aimed to reveal the genetic background of patients in the two-generation family suffering from rheumatoid arthritis, psoriatic arthropathy pain, scratches, and bruises.\n            \n            \n              Patients and methods:\n              A clinical exome sequencing analysis was performed in 10 individuals in the same family using the Sophia Genetics clinical exome solution kit.\n            \n            \n              Results:\n              A novel V194L mutation in the TMEM173 gene was identified in three members of the family. Two of the family members were treated with the JAK3 inhibitor tofacitinib and recovered completely one month after the treatment.\n            \n            \n              Conclusion:\n              The V194L mutation was reported for the first time in this study, and a positive response was achieved with tofacitinib.},\n\tlanguage = {en},\n\turldate = {2023-03-09},\n\tjournal = {Archives of Rheumatology},\n\tauthor = {Elvan Tokgun, Pervin and Karagenc, Nedim and Karasu, Uğur and Tokgun, Onur and Turel, Samet and Demiray, Aydın and Akca, Hakan and Yüksel, Selçuk},\n\tmonth = feb,\n\tyear = {2023},\n\tkeywords = {CES, DDM},\n\tpages = {1443},\n}\n\n

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\n \n\n \n \n \n \n \n \n Functional Analyses of Rare Germline Missense BRCA1 Variants Located within and outside Protein Domains with Known Functions.\n \n \n \n \n\n\n \n Hovland, H. N.; Mchaina, E. K.; Høberg-Vetti, H.; Ariansen, S. L.; Sjursen, W.; Van Ghelue, M.; Haukanes, B. I.; Knappskog, P. M.; Aukrust, I.; and Ognedal, E.\n\n\n \n\n\n\n Genes, 14(2): 262. January 2023.\n Number: 2 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Functional$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{hovland_functional_2023,\n\ttitle = {Functional {Analyses} of {Rare} {Germline} {Missense} {BRCA1} {Variants} {Located} within and outside {Protein} {Domains} with {Known} {Functions}},\n\tvolume = {14},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2073-4425},\n\turl = {https://www.mdpi.com/2073-4425/14/2/262},\n\tdoi = {10.3390/genes14020262},\n\tabstract = {The BRCA1 protein is implicated in numerous important cellular processes to prevent genomic instability and tumorigenesis, and pathogenic germline variants predispose carriers to hereditary breast and ovarian cancer (HBOC). Most functional studies of missense variants in BRCA1 focus on variants located within the Really Interesting New Gene (RING), coiled-coil and BRCA1 C-terminal (BRCT) domains, and several missense variants in these regions have been shown to be pathogenic. However, the majority of these studies focus on domain specific assays, and have been performed using isolated protein domains and not the full-length BRCA1 protein. Furthermore, it has been suggested that BRCA1 missense variants located outside domains with known function are of no functional importance, and could be classified as (likely) benign. However, very little is known about the role of the regions outside the well-established domains of BRCA1, and only a few functional studies of missense variants located within these regions have been published. In this study, we have, therefore, functionally evaluated the effect of 14 rare BRCA1 missense variants considered to be of uncertain clinical significance, of which 13 are located outside the well-established domains and one within the RING domain. In order to investigate the hypothesis stating that most BRCA1 variants located outside the known protein domains are benign and of no functional importance, multiple protein assays including protein expression and stability, subcellular localisation and protein interactions have been performed, utilising the full-length protein to better mimic the native state of the protein. Two variants located outside the known domains (p.Met297Val and p.Asp1152Asn) and one variant within the RING domain (p.Leu52Phe) were found to make the BRCA1 protein more prone to proteasome-mediated degradation. In addition, two variants (p.Leu1439Phe and p.Gly890Arg) also located outside known domains were found to have reduced protein stability compared to the wild type protein. These findings indicate that variants located outside the RING, BRCT and coiled-coiled domains could also affect the BRCA1 protein function. For the nine remaining variants, no significant effects on BRCA1 protein functions were observed. Based on this, a reclassification of seven variants from VUS to likely benign could be suggested.},\n\tlanguage = {en},\n\tnumber = {2},\n\turldate = {2023-03-09},\n\tjournal = {Genes},\n\tauthor = {Hovland, Henrikke Nilsen and Mchaina, Eunice Kabanyana and Høberg-Vetti, Hildegunn and Ariansen, Sarah Louise and Sjursen, Wenche and Van Ghelue, Marijke and Haukanes, Bjørn Ivar and Knappskog, Per Morten and Aukrust, Ingvild and Ognedal, Elisabet},\n\tmonth = jan,\n\tyear = {2023},\n\tnote = {Number: 2\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Alamut, Alamut Visual v2.15},\n\tpages = {262},\n}\n\n

\n\n\n

\n The BRCA1 protein is implicated in numerous important cellular processes to prevent genomic instability and tumorigenesis, and pathogenic germline variants predispose carriers to hereditary breast and ovarian cancer (HBOC). Most functional studies of missense variants in BRCA1 focus on variants located within the Really Interesting New Gene (RING), coiled-coil and BRCA1 C-terminal (BRCT) domains, and several missense variants in these regions have been shown to be pathogenic. However, the majority of these studies focus on domain specific assays, and have been performed using isolated protein domains and not the full-length BRCA1 protein. Furthermore, it has been suggested that BRCA1 missense variants located outside domains with known function are of no functional importance, and could be classified as (likely) benign. However, very little is known about the role of the regions outside the well-established domains of BRCA1, and only a few functional studies of missense variants located within these regions have been published. In this study, we have, therefore, functionally evaluated the effect of 14 rare BRCA1 missense variants considered to be of uncertain clinical significance, of which 13 are located outside the well-established domains and one within the RING domain. In order to investigate the hypothesis stating that most BRCA1 variants located outside the known protein domains are benign and of no functional importance, multiple protein assays including protein expression and stability, subcellular localisation and protein interactions have been performed, utilising the full-length protein to better mimic the native state of the protein. Two variants located outside the known domains (p.Met297Val and p.Asp1152Asn) and one variant within the RING domain (p.Leu52Phe) were found to make the BRCA1 protein more prone to proteasome-mediated degradation. In addition, two variants (p.Leu1439Phe and p.Gly890Arg) also located outside known domains were found to have reduced protein stability compared to the wild type protein. These findings indicate that variants located outside the RING, BRCT and coiled-coiled domains could also affect the BRCA1 protein function. For the nine remaining variants, no significant effects on BRCA1 protein functions were observed. Based on this, a reclassification of seven variants from VUS to likely benign could be suggested.\n

\n\n\n

\n \n\n \n \n \n \n \n \n Viral Population Heterogeneity and Fluctuating Mutational Pattern during a Persistent SARS-CoV-2 Infection in an Immunocompromised Patient.\n \n \n \n \n\n\n \n Brandolini, M.; Zannoli, S.; Gatti, G.; Arfilli, V.; Cricca, M.; Dirani, G.; Denicolò, A.; Semprini, S.; Grumiro, L.; Imola, M.; Larne, D.; Marino, M. M.; Manera, M.; Mancini, A.; Taddei, F.; Zagarrigo, M.; Biagetti, C.; and Sambri, V.\n\n\n \n\n\n\n Viruses, 15(2): 291. January 2023.\n Number: 2 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Viral$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{brandolini_viral_2023,\n\ttitle = {Viral {Population} {Heterogeneity} and {Fluctuating} {Mutational} {Pattern} during a {Persistent} {SARS}-{CoV}-2 {Infection} in an {Immunocompromised} {Patient}},\n\tvolume = {15},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {1999-4915},\n\turl = {https://www.mdpi.com/1999-4915/15/2/291},\n\tdoi = {10.3390/v15020291},\n\tabstract = {Literature offers plenty of cases of immunocompromised patients, who develop chronic and severe SARS-CoV-2 infections. The aim of this study is to provide further insight into SARS-CoV-2 evolutionary dynamic taking into exam a subject suffering from follicular lymphoma, who developed a persistent infection for over 7 months. Eight nasopharyngeal swabs were obtained, and were analyses by qRT-PCR for diagnostic purposes. All of them were considered eligible (Ct {\\textless} 30) for NGS sequencing. Sequence analysis showed that all sequences matched the B.1.617.2 AY.122 lineage, but they differed by few mutations identifying three genetically similar subpopulations, which evolved during the course of infection, demonstrating that prolonged replication is paralleled with intra-host virus evolution. These evidences support the hypothesis that SARS-CoV-2 adaptive capacities are able to shape a heterogeneous viral population in the context of immunocompromised patients. Spill-over of viral variants with enhanced transmissibility or immune escape capacities from these subjects is plausible.},\n\tlanguage = {en},\n\tnumber = {2},\n\turldate = {2023-03-09},\n\tjournal = {Viruses},\n\tauthor = {Brandolini, Martina and Zannoli, Silvia and Gatti, Giulia and Arfilli, Valentina and Cricca, Monica and Dirani, Giorgio and Denicolò, Agnese and Semprini, Simona and Grumiro, Laura and Imola, Manuela and Larne, Damiano and Marino, Maria Michela and Manera, Martina and Mancini, Andrea and Taddei, Francesca and Zagarrigo, Manuel and Biagetti, Carlo and Sambri, Vittorio},\n\tmonth = jan,\n\tyear = {2023},\n\tnote = {Number: 2\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {DDM, DDM v.4, SARS-CoV-2},\n\tpages = {291},\n}\n\n

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\n \n\n \n \n \n \n \n Multigene Panel Testing in Turkish Hereditary Cancer Syndrome Patients.\n \n \n \n\n\n \n Arslan Ates, E.; Turkyilmaz, A.; Alavanda, C.; Yildirim, O.; and Guney, A. I.\n\n\n \n\n\n\n Medeniyet Medical Journal, 37(2): 150–158. January 2023.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{arslan_ates_multigene_2023,\n\ttitle = {Multigene {Panel} {Testing} in {Turkish} {Hereditary} {Cancer} {Syndrome} {Patients}},\n\tvolume = {37},\n\tissn = {2149-2042},\n\tdoi = {10.4274/MMJ.galenos.2022.22556},\n\tabstract = {OBJECTIVE: Hereditary cancer syndromes (HCSs) are a heterogenous group of disorders caused by germline pathogenic variations in various genes that function in cell growth and proliferation. This study aimed to describe the germline variations in patients with hereditary cancer using multigene panels.\nMETHODS: The molecular and clinical findings of 218 patients with HCS were evaluated. In addition, 25 HCS-related genes were sequenced using a multigene panel, and variations were classified according to the American College of Medical Genetics and Genomics (ACMG) criteria. In total, 218 HCS patients predominantly with breast, colorectal, ovarian, gastric, and endometrium cancers were included.\nRESULTS: Pathogenic variations in 12 distinct genes were detected in 36 of 218 (16.5\\%) cases. In this study, the most affected gene was the ATM gene, in which pathogenic variations were detected in 8 of 218 cases, followed by CHEK2 (3.2\\%), MUTYH (3.2\\%), BRIP1 (1.8\\%), BARD1 (0.9\\%), TP53 (0.9\\%), PALB2 (0.4\\%), MLH1 (0.4\\%), MSH2 (0.4\\%), PMS2 (0.4\\%), RAD50 (0.4\\%), and RAD51C (0.4\\%).\nCONCLUSIONS: This study contributes to genotype-phenotype correlation in HCSs and expands the variation spectrum by introducing three novel pathogenic variations. The wide spectrum of the gene pathogenic variations detected and the presence of multiple gene defects in the same patient make the multigene panel testing a valuable tool in detecting the hereditary forms of cancer and providing effective genetic counseling and family specific screening strategies.\nAMAÇ: Herediter kanser sendromları (HCS) hücre büyümesi ve proliferasyonunda görevli genlerde saptanan germline mutasyonlardan kaynaklanan heterojen bir grup hastalıktır. Bu çalışmada kalıtımsal kanser sendrom ön tanısıyla değerlendirilen olgularda çoklu gen paneli ile germ hattı varyasyonlarının değerlendirilmesi planlanmıştır.\nYÖNTEMLER: Kalıtımsal kanser sendromu düşünülen 218 olgudan periferik kandan DNA izolasyonu sonrası HCS ile ilişkili 25 gen multigen panel kullanılarak dizilendi ve varyasyonlar American College of Medical Genetics and Genomics (ACMG) kriterlerine göre değerlendirildi.\nBULGULAR: Meme, kolorektal, over, gastrik ve endometriyum kanseri başta olmak üzere toplam 218 herediter kanser sendromlu olgu değerlendirildi. Tüm çalışma grubu incelendiğinde en sık ATM gen varyasyonları (8/218, \\%3,6) tespit edildi ve bunu sıklık sırasına göre CHEK2 (\\%3,2), MUTYH (\\%3,2), BRIP1 (\\%1,8), BARD1 (\\%0,9), TP53 (\\%0,9), PALB2 (\\%0,4), MLH1 (\\%0,4), MSH2 (\\%0,4), PMS2 (\\%0,4), RAD50 (\\%0,4), RAD51C (\\%0,4) varyasyonları takip etmekteydi.\nSONUÇLAR: Bu çalışmada farklı kanser türlerinde kalıtımsal kansere yol açan genler analiz edilmiş ve fenotiple ilişkisi değerlendirilmiştir. Ayrıca bu çalışmada ilk kez saptanan üç yeni varyasyon ile literatüre katkı sağlanmaktadır. Patojenik varyasyon tespit edilen genlerin geniş dağılımı ve aynı hastada birden fazla genetik varyasyonun varlığı düşünüldüğünde, uygun genetik danışma ve aileye özgü tarama planlaması yapmak için çoklu gen taraması kalıtımsal kanser hastalarının değerlendirilmesinde hızlı ve etkin bir yöntem olarak görünmektedir.},\n\tlanguage = {eng},\n\tnumber = {2},\n\tjournal = {Medeniyet Medical Journal},\n\tauthor = {Arslan Ates, Esra and Turkyilmaz, Ayberk and Alavanda, Ceren and Yildirim, Ozlem and Guney, Ahmet Ilter},\n\tmonth = jan,\n\tyear = {2023},\n\tpmid = {35734982},\n\tpmcid = {PMC9234359},\n\tkeywords = {DDM, HCS v.1},\n\tpages = {150--158},\n}\n\n

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\n OBJECTIVE: Hereditary cancer syndromes (HCSs) are a heterogenous group of disorders caused by germline pathogenic variations in various genes that function in cell growth and proliferation. This study aimed to describe the germline variations in patients with hereditary cancer using multigene panels. METHODS: The molecular and clinical findings of 218 patients with HCS were evaluated. In addition, 25 HCS-related genes were sequenced using a multigene panel, and variations were classified according to the American College of Medical Genetics and Genomics (ACMG) criteria. In total, 218 HCS patients predominantly with breast, colorectal, ovarian, gastric, and endometrium cancers were included. RESULTS: Pathogenic variations in 12 distinct genes were detected in 36 of 218 (16.5%) cases. In this study, the most affected gene was the ATM gene, in which pathogenic variations were detected in 8 of 218 cases, followed by CHEK2 (3.2%), MUTYH (3.2%), BRIP1 (1.8%), BARD1 (0.9%), TP53 (0.9%), PALB2 (0.4%), MLH1 (0.4%), MSH2 (0.4%), PMS2 (0.4%), RAD50 (0.4%), and RAD51C (0.4%). CONCLUSIONS: This study contributes to genotype-phenotype correlation in HCSs and expands the variation spectrum by introducing three novel pathogenic variations. The wide spectrum of the gene pathogenic variations detected and the presence of multiple gene defects in the same patient make the multigene panel testing a valuable tool in detecting the hereditary forms of cancer and providing effective genetic counseling and family specific screening strategies. AMAÇ: Herediter kanser sendromları (HCS) hücre büyümesi ve proliferasyonunda görevli genlerde saptanan germline mutasyonlardan kaynaklanan heterojen bir grup hastalıktır. Bu çalışmada kalıtımsal kanser sendrom ön tanısıyla değerlendirilen olgularda çoklu gen paneli ile germ hattı varyasyonlarının değerlendirilmesi planlanmıştır. YÖNTEMLER: Kalıtımsal kanser sendromu düşünülen 218 olgudan periferik kandan DNA izolasyonu sonrası HCS ile ilişkili 25 gen multigen panel kullanılarak dizilendi ve varyasyonlar American College of Medical Genetics and Genomics (ACMG) kriterlerine göre değerlendirildi. BULGULAR: Meme, kolorektal, over, gastrik ve endometriyum kanseri başta olmak üzere toplam 218 herediter kanser sendromlu olgu değerlendirildi. Tüm çalışma grubu incelendiğinde en sık ATM gen varyasyonları (8/218, %3,6) tespit edildi ve bunu sıklık sırasına göre CHEK2 (%3,2), MUTYH (%3,2), BRIP1 (%1,8), BARD1 (%0,9), TP53 (%0,9), PALB2 (%0,4), MLH1 (%0,4), MSH2 (%0,4), PMS2 (%0,4), RAD50 (%0,4), RAD51C (%0,4) varyasyonları takip etmekteydi. SONUÇLAR: Bu çalışmada farklı kanser türlerinde kalıtımsal kansere yol açan genler analiz edilmiş ve fenotiple ilişkisi değerlendirilmiştir. Ayrıca bu çalışmada ilk kez saptanan üç yeni varyasyon ile literatüre katkı sağlanmaktadır. Patojenik varyasyon tespit edilen genlerin geniş dağılımı ve aynı hastada birden fazla genetik varyasyonun varlığı düşünüldüğünde, uygun genetik danışma ve aileye özgü tarama planlaması yapmak için çoklu gen taraması kalıtımsal kanser hastalarının değerlendirilmesinde hızlı ve etkin bir yöntem olarak görünmektedir.\n

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\n \n\n \n \n \n \n \n \n Combined exome analysis and exome depth assessment achieves a high diagnostic yield in an epilepsy case series, revealing significant genomic heterogeneity and novel mechanisms.\n \n \n \n \n\n\n \n Veltra, D.; Tilemis, F.; Marinakis, N. M.; Svingou, M.; Mitrakos, A.; Kosma, K.; Tsoutsou, I.; Makrythanasis, P.; Theodorou, V.; Katsalouli, M.; Vorgia, P.; Niotakis, G.; Vartzelis, G.; Dinopoulos, A.; Evangeliou, A.; Mouskou, S.; Korona, A.; Mastroyianni, S.; Papavasiliou, A.; Tzetis, M.; Pons, R.; Traeger-Synodinos, J.; and Sofocleous, C.\n\n\n \n\n\n\n Expert Review of Molecular Diagnostics, 0(ja): null. January 2023.\n Publisher: Taylor & Francis _eprint: https://doi.org/10.1080/14737159.2023.2173578\n\n\n\n
\n\n\n\n \n \n $\"Combined$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{veltra_combined_2023,\n\ttitle = {Combined exome analysis and exome depth assessment achieves a high diagnostic yield in an epilepsy case series, revealing significant genomic heterogeneity and novel mechanisms},\n\tvolume = {0},\n\tissn = {1473-7159},\n\turl = {https://doi.org/10.1080/14737159.2023.2173578},\n\tdoi = {10.1080/14737159.2023.2173578},\n\tabstract = {Objectives The genetics of epilepsy are highly heterogenous and often complex. Lesions detected involve genes encoding various types of channels, transcription factors, and other proteins implicated in numerous cellular processes, such as synaptogenesis. Consequently, a wide spectrum of clinical presentations and overlapping phenotypes, hinders differential diagnosis and highlights the need for molecular investigations towards delineation of underlying mechanisms and final diagnosis. Characterization of defects may also contribute valuable data on genetic landscapes and networks implicated in epileptogenesis.Methods This study reports on genetic findings from exome sequencing (ES) data of 107 patients with variable types of seizures, with or without additional symptoms, in the context of neurodevelopmental disorders.Results Multidisciplinary evaluation of ES, including ancillary detection of Copy Number Variants (CNVs) with the ExomeDepth tool, supported a definite diagnosis in 59.8\\% of the patients, reflecting one of the highest diagnostic yields in epilepsy.Conclusion Emerging advances of next generation technologies and “in silico” analysis tools offer the possibility to simultaneously detect several types of variations. Wide assessment of variable findings, specifically those found to be novel and least expected, reflect the ever-evolving genetic landscape of seizure development, potentially beneficial for increased opportunities for trial recruitment and enrollment, and optimized, even personalized, medical management.},\n\tnumber = {ja},\n\turldate = {2023-02-08},\n\tjournal = {Expert Review of Molecular Diagnostics},\n\tauthor = {Veltra, Danai and Tilemis, Faidon-Nikolaos and Marinakis, Nikolaos M. and Svingou, Maria and Mitrakos, Anastasios and Kosma, Konstantina and Tsoutsou, Irene and Makrythanasis, Periklis and Theodorou, Virginia and Katsalouli, Marina and Vorgia, Pelagia and Niotakis, Georgios and Vartzelis, Georgios and Dinopoulos, Argirios and Evangeliou, Athanasios and Mouskou, Stella and Korona, Anastasia and Mastroyianni, Sotiria and Papavasiliou, Antigone and Tzetis, Maria and Pons, Roser and Traeger-Synodinos, Joanne and Sofocleous, Christalena},\n\tmonth = jan,\n\tyear = {2023},\n\tpmid = {36714946},\n\tnote = {Publisher: Taylor \\& Francis\n\\_eprint: https://doi.org/10.1080/14737159.2023.2173578},\n\tkeywords = {Epilepsy case series, genotype, novel variants, phenotype},\n\tpages = {null},\n}\n\n

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\n \n\n \n \n \n \n \n \n Trabectedin – LY3009120 inhibitor.\n \n \n \n \n\n\n \n \n\n\n \n\n\n\n January 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Trabectedin$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@misc{noauthor_trabectedin_2023,\n\ttitle = {Trabectedin – {LY3009120} inhibitor},\n\turl = {https://ly3009120inhibitor.com/trabectedin/},\n\tabstract = {LY3009120 is a pan-Raf kinase inhibitor},\n\tlanguage = {en-US},\n\turldate = {2023-02-08},\n\tmonth = jan,\n\tyear = {2023},\n\tkeywords = {Declaration of interest},\n}\n\n

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\n \n\n \n \n \n \n \n \n 3q29 microduplication syndrome: New evidence for the refinement of the critical region.\n \n \n \n \n\n\n \n Bauleo, A.; Pace, V.; Montesanto, A.; De Stefano, L.; Brando, R.; Puntorieri, D.; Cento, L.; Genuardi, M.; and Falcone, E.\n\n\n \n\n\n\n Molecular Genetics & Genomic Medicine, n/a(n/a): e2130. January 2023.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/mgg3.2130\n\n\n\n
\n\n\n\n \n \n $\"3q29$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{bauleo_3q29_2023,\n\ttitle = {3q29 microduplication syndrome: {New} evidence for the refinement of the critical region},\n\tvolume = {n/a},\n\tissn = {2324-9269},\n\tshorttitle = {3q29 microduplication syndrome},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/mgg3.2130},\n\tdoi = {10.1002/mgg3.2130},\n\tabstract = {Background The 3q29 microduplication syndrome is a rare genomic disorder characterized by an extremely variable neurodevelopmental phenotype usually involving a genomic region ranging from 1.6 to 1.76 Mb. A small microduplication of 448.8 Kb containing only two genes was recently described in a patient with a 3q29 microduplication that was proposed as the minimal critical region of overlap of this syndrome. Methods Molecular karyotyping (array-CGH) was performed on DNA extracted from peripheral blood samples using Agilent-California USA Human Genome CGH Microarray 4 × 180 K. The proband and his younger brother were further tested with a next generation sequencing (NGS) panel including genes implicated in autism spectrum disorder and in neurodevelopmental disorders. Quantitative real-time PCR was applied to verify the abnormal array-CGH findings. Results Here, we report on a family with two males with neurodevelopmental disorders and an unaffected sibling with a small 3q29 microduplication (432.8 Kb) inherited from an unaffected mother that involves only two genes: DGL1 and BDH1. The proband had an additional intragenic duplication inherited from the unaffected father. Further testing was negative for Fragile X syndrome and for genes implicated in autism spectrum disorder and in neurodevelopmental disorders. Conclusion To the best of our knowledge, one of the family members here analyzed is the second reported case of a patient carrying a small 3q29 microduplication including only DGL1 and BDH1 genes and without any additional genetic aberration. The recognition of the clinical spectrum in patients with the critical region of overlap associated with the 3q29 duplication syndrome should prove valuable for predicting outcomes and providing more informed genetic counseling to patients with duplications in this region.},\n\tlanguage = {en},\n\tnumber = {n/a},\n\turldate = {2023-02-08},\n\tjournal = {Molecular Genetics \\& Genomic Medicine},\n\tauthor = {Bauleo, Alessia and Pace, Vincenza and Montesanto, Alberto and De Stefano, Laura and Brando, Rossella and Puntorieri, Domenica and Cento, Luca and Genuardi, Maurizio and Falcone, Elena},\n\tmonth = jan,\n\tyear = {2023},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/mgg3.2130},\n\tkeywords = {3q29 microduplication, CES, DDM v5.10.4, array-CGH, neurodevelopmental phenotypes},\n\tpages = {e2130},\n}\n\n

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\n \n\n \n \n \n \n \n \n Primary thyroid rhabdomyosarcoma in an adult: a challenging case with histomolecular diagnosis and literature review.\n \n \n \n \n\n\n \n Alsugair, Z.; Calcagno, F.; Lifante, J.; Descotes, F.; Lopez, J.; Zirganos, N.; Charon-Barra, C.; Meurgey, A.; and Decaussin-Petrucci, M.\n\n\n \n\n\n\n Technical Report In Review, January 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Primary$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@techreport{alsugair_primary_2023,\n\ttype = {preprint},\n\ttitle = {Primary thyroid rhabdomyosarcoma in an adult: a challenging case with histomolecular diagnosis and literature review},\n\tshorttitle = {Primary thyroid rhabdomyosarcoma in an adult},\n\turl = {https://www.researchsquare.com/article/rs-2483550/v1},\n\tabstract = {Abstract\n          \n            We report a case of primary thyroid rhabdomyosarcoma in a 61-year-old woman. Histologically, the neoplasm was composed of sheets of pleomorphic or spindle-shaped cells with eosinophilic cytoplasm and few large and very pleomorphic cells admixed with the spindle cell proliferation, without any thyroid epithelial component. Immunohistochemically, the tumour cells were positive for muscular markers and negative for epithelial and thyroid differentiation markers (AE1-AE3, EMA, CK5/6, TTF1, PAX8, thyroglobulin). Molecular tests revealed the presence of\n            NF1\n            ,\n            PTEN\n            and\n            TERT\n            pathogenic mutations. Major morphological differential diagnoses include anaplastic thyroid carcinoma with rhabdoid phenotype, leiomyosarcoma, as well as other rare sarcomas. In this study, we describe the fifth case in the literature of primary thyroid rhabdomyosarcoma and the third in adults with, for the first time, an extensive molecular analysis.},\n\tlanguage = {en},\n\turldate = {2023-02-08},\n\tinstitution = {In Review},\n\tauthor = {Alsugair, Ziyad and Calcagno, Fabien and Lifante, Jean-Christophe and Descotes, Francoise and Lopez, Jonathan and Zirganos, Nikolaos and Charon-Barra, Céline and Meurgey, Alexandra and Decaussin-Petrucci, Myriam},\n\tmonth = jan,\n\tyear = {2023},\n\tdoi = {10.21203/rs.3.rs-2483550/v1},\n\tkeywords = {Custom Cancer Panel, Custom Panel, pan-cancer},\n}\n\n

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\n \n\n \n \n \n \n \n \n Machine-learning approach for prediction of pT3a upstaging and outcomes of localized renal cell carcinoma (UroCCR-15).\n \n \n \n \n\n\n \n Boulenger de Hauteclocque, A.; Ferrer, L.; Ambrosetti, D.; Ricard, S.; Bigot, P.; Bensalah, K.; Henon, F.; Doumerc, N.; Méjean, A.; Verkarre, V.; Dariane, C.; Larré, S.; Champy, C.; de La Taille, A.; Bruyère, F.; Rouprêt, M.; Paparel, P.; Droupy, S.; Fontenil, A.; Patard, J.; Durand, X.; Waeckel, T.; Lang, H.; Lebâcle, C.; Guy, L.; Pignot, G.; Durand, M.; Long, J.; Charles, T.; Xylinas, E.; Boissier, R.; Yacoub, M.; Colin, T.; and Bernhard, J.\n\n\n \n\n\n\n BJU International, n/a(n/a). January 2023.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/bju.15959\n\n\n\n
\n\n\n\n \n \n $\"Machine-learning$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{boulenger_de_hauteclocque_machine-learning_2023,\n\ttitle = {Machine-learning approach for prediction of {pT3a} upstaging and outcomes of localized renal cell carcinoma ({UroCCR}-15)},\n\tvolume = {n/a},\n\tissn = {1464-410X},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1111/bju.15959},\n\tdoi = {10.1111/bju.15959},\n\tabstract = {Objectives To assess the impact of pathological upstaging from clinically localized to locally advanced pT3a on survival in patients with renal cell carcinoma (RCC), as well as the oncological safety of various surgical approaches in this setting, and to develop a machine-learning-based, contemporary, clinically relevant model for individual preoperative prediction of pT3a upstaging. Materials and Methods Clinical data from patients treated with either partial nephrectomy (PN) or radical nephrectomy (RN) for cT1/cT2a RCC from 2000 to 2019, included in the French multi-institutional kidney cancer database UroCCR, were retrospectively analysed. Seven machine-learning algorithms were applied to the cohort after a training/testing split to develop a predictive model for upstaging to pT3a. Survival curves for disease-free survival (DFS) and overall survival (OS) rates were compared between PN and RN after G-computation for pT3a tumours. Results A total of 4395 patients were included, among whom 667 patients (15\\%, 337 PN and 330 RN) had a pT3a-upstaged RCC. The UroCCR-15 predictive model presented an area under the receiver-operating characteristic curve of 0.77. Survival analysis after adjustment for confounders showed no difference in DFS or OS for PN vs RN in pT3a tumours (DFS: hazard ratio [HR] 1.08, P = 0.7; OS: HR 1.03, P {\\textgreater} 0.9). Conclusions Our study shows that machine-learning technology can play a useful role in the evaluation and prognosis of upstaged RCC. In the context of incidental upstaging, PN does not compromise oncological outcomes, even for large tumour sizes.},\n\tlanguage = {en},\n\tnumber = {n/a},\n\turldate = {2023-02-08},\n\tjournal = {BJU International},\n\tauthor = {Boulenger de Hauteclocque, Astrid and Ferrer, Loïc and Ambrosetti, Damien and Ricard, Solene and Bigot, Pierre and Bensalah, Karim and Henon, François and Doumerc, Nicolas and Méjean, Arnaud and Verkarre, Virginie and Dariane, Charles and Larré, Stéphane and Champy, Cécile and de La Taille, Alexandre and Bruyère, Franck and Rouprêt, Morgan and Paparel, Philippe and Droupy, Stéphane and Fontenil, Alexis and Patard, Jean-Jacques and Durand, Xavier and Waeckel, Thibaut and Lang, Herve and Lebâcle, Cédric and Guy, Laurent and Pignot, Geraldine and Durand, Matthieu and Long, Jean-Alexandre and Charles, Thomas and Xylinas, Evanguelos and Boissier, Romain and Yacoub, Mokrane and Colin, Thierry and Bernhard, Jean-Christophe},\n\tmonth = jan,\n\tyear = {2023},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/bju.15959},\n\tkeywords = {TNM staging, disease-free survival, machine learning, partial nephrectomy, renal cell carcinoma},\n}\n\n

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\n \n\n \n \n \n \n \n \n Combined Reverse-Transcriptase Multiplex Ligation-Dependent Probe Amplification and Next-Generation Sequencing Analyses to Assign Unclassified BCL2−/BCL6− Nonrearranged Small B-Cell Lymphoid Neoplasms as Follicular or Nodal Marginal Zone Lymphoma.\n \n \n \n \n\n\n \n Sesboue, C.; Galtier, J.; Jeanneau, M.; Chauvel, A.; Laharanne, E.; Amintas, S.; Merlio, J.; Bouabdallah, K.; Gros, F.; de Leval, L.; Gros, A.; and Parrens, M.\n\n\n \n\n\n\n Modern Pathology, 36(2): 100043. January 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Combined$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{sesboue_combined_2023,\n\ttitle = {Combined {Reverse}-{Transcriptase} {Multiplex} {Ligation}-{Dependent} {Probe} {Amplification} and {Next}-{Generation} {Sequencing} {Analyses} to {Assign} {Unclassified} {BCL2}−/{BCL6}− {Nonrearranged} {Small} {B}-{Cell} {Lymphoid} {Neoplasms} as {Follicular} or {Nodal} {Marginal} {Zone} {Lymphoma}},\n\tvolume = {36},\n\tissn = {0893-3952},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0893395222000436},\n\tdoi = {10.1016/j.modpat.2022.100043},\n\tabstract = {Distinguishing between follicular lymphoma (FL) and nodal marginal zone lymphoma (NMZL) can be difficult when morphologic and phenotypic features are unusual and characteristic cytogenetic rearrangements are absent. We evaluated the diagnostic contribution of ancillary techniques—including fluorescence in situ hybridization (FISH)-detected 1p36 deletion; reverse-transcriptase, multiplex, ligation-dependent probe amplification (RT-MLPA); and next-generation sequencing (NGS)—for tumors that remain unclassified according to standard criteria. After review, 50 CD5-negative small B-cell lymphoid neoplasms without BCL2 and BCL6 FISH rearrangements were diagnosed as FLs (n = 27), NMZLs (n = 5), or unclassified (n = 18) based on the 2016 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. FISH helped identify the 1p36 deletion in 3 FLs and 1 unclassified tumor. Most classified FLs had an RT-MLPA germinal center B-cell (GCB) signature (93\\%) or were noncontributive (7\\%). Classified NMZLs had an RT-MLPA activated B-cell signature (20\\%), had an unassigned signature (40\\%), or were noncontributive (40\\%). Among unclassified tumors, the RT-MLPA GCB signature was associated with mutations most commonly found in FLs (CREBBP, EZH2, STAT6, and/or TNFRSF14) (90\\%). An RT-MLPA-detected GCB signature and/or NGS-detected gene mutations were considered as FL identifiers for 13 tumors. An activated B-cell signature or NOTCH2 mutation supported NMZL diagnosis in 3 tumors. Combining the RT-MLPA and NGS findings successfully discriminated 89\\% of unclassified tumors in favor of one or the other diagnosis. NGS-detected mutations may be of therapeutic interest. Herein, we detected 3 EZH2 and 8 CREBBP mutations that might be eligible for targeted therapies.},\n\tlanguage = {en},\n\tnumber = {2},\n\turldate = {2023-02-08},\n\tjournal = {Modern Pathology},\n\tauthor = {Sesboue, Come and Galtier, Jean and Jeanneau, Marie and Chauvel, Annick and Laharanne, Elodie and Amintas, Samuel and Merlio, Jean-Philippe and Bouabdallah, Krimo and Gros, François-Xavier and de Leval, Laurence and Gros, Audrey and Parrens, Marie},\n\tmonth = jan,\n\tyear = {2023},\n\tkeywords = {FISH, NGS, RT-MLPA, Small B-cell lymphoid neoplasm},\n\tpages = {100043},\n}\n\n

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\n \n\n \n \n \n \n \n \n Homologous Recombination Repair Deficiency: An Overview for Pathologists.\n \n \n \n \n\n\n \n Doig, K. D.; Fellowes, A. P.; and Fox, S. B.\n\n\n \n\n\n\n Modern Pathology,100049. January 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Homologous$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{doig_homologous_2023,\n\ttitle = {Homologous {Recombination} {Repair} {Deficiency}: {An} {Overview} for {Pathologists}},\n\tissn = {0893-3952},\n\tshorttitle = {Homologous {Recombination} {Repair} {Deficiency}},\n\turl = {https://www.sciencedirect.com/science/article/pii/S089339522200480X},\n\tdoi = {10.1016/j.modpat.2022.100049},\n\tabstract = {The repair of DNA double-stranded breaks relies on the homologous recombination repair pathway and is critical to cell function. However, this pathway can be lost in some cancers such as breast, ovarian, endometrial, pancreatic, and prostate cancers. Cancer cells with homologous recombination deficiency (HRD) are sensitive to targeted inhibition of poly-ADP ribose polymerase (PARP), a key component of alternative backup DNA repair pathways. Identifying patients with cancer with HRD biomarkers allows the identification of patients likely to benefit from PARP inhibitor therapies. In this study, we describe the causes of HRD, the underlying molecular changes resulting from HRD that form the basis of different molecular HRD assays, and discuss the issues around their clinical use. This overview is directed toward practicing pathologists wishing to be informed of this new predictive biomarker, as PARP inhibitors are increasingly used in standard care settings.},\n\tlanguage = {en},\n\turldate = {2023-02-08},\n\tjournal = {Modern Pathology},\n\tauthor = {Doig, Kenneth D. and Fellowes, Andrew P. and Fox, Stephen B.},\n\tmonth = jan,\n\tyear = {2023},\n\tkeywords = {DDM, HRD, PARPi, molecular diagnostics},\n\tpages = {100049},\n}\n\n

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\n \n\n \n \n \n \n \n \n Nonsalivary Primary Adenocarcinomas of the Base of Tongue: A Single Tertiary-Care Oncology Center Series of 6 Cases.\n \n \n \n \n\n\n \n Yadav, S.; Mittal, N.; Rane, S. U.; Bal, M.; Patil, A.; Ankathi, S. K.; and Nair, D.\n\n\n \n\n\n\n Archives of Pathology & Laboratory Medicine. January 2023.\n \n\n\n\n
\n\n\n\n \n \n $\"Nonsalivary$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{yadav_nonsalivary_2023,\n\ttitle = {Nonsalivary {Primary} {Adenocarcinomas} of the {Base} of {Tongue}: {A} {Single} {Tertiary}-{Care} {Oncology} {Center} {Series} of 6 {Cases}},\n\tissn = {0003-9985},\n\tshorttitle = {Nonsalivary {Primary} {Adenocarcinomas} of the {Base} of {Tongue}},\n\turl = {https://doi.org/10.5858/arpa.2021-0468-OA},\n\tdoi = {10.5858/arpa.2021-0468-OA},\n\tabstract = {Nonsalivary primary adenocarcinomas of the base of tongue (PABOTs) are extremely rare and worth reporting.To study the detailed clinicopathologic features of PABOT.Cases of PABOT diagnosed on pathology material were retrieved from the archived electronic surgical pathology records.Six cases in 4 men and 2 women (M:F ratio, 2:1), with an age range of 31 to 76 years, satisfied the criteria. The tumor epicenter was the base of tongue in all (6 of 6; 100\\%), with extension to the epiglottis in 50\\% (3 of 6), nodal metastasis in 66.7\\% (4 of 6), and distant metastasis in 33.3\\% (2 of 6). On histology, all but one were pure adenocarcinoma. Five of 6 cases (83.3\\%) had a gastrointestinal (GI) phenotype, of which 2 (40\\%) had a colonic/lower-GI–type (small groups of cells floating in mucin, CK20+, SATB2+, and CDX2+) and 3 (60\\%) had an upper-GI–like adenocarcinoma (UGI-LA; malignant glands with intracellular mucin, CK7+) histology. Cystic structure suggestive of teratomatous origin was identified in 2 of 5 cases (40\\%), both with UGI-LA phenotype. The non–GI-type case had a unique histology with squamous differentiation in addition to adenocarcinoma areas, diffuse nuclear β-catenin on immunohistochemistry, and a corresponding exon 3 CTNNB1 mutation. One patient succumbed to disease, and 4 are alive with disease (follow-up of 1–9 months after completion of therapy).We suggest using the broad term primary adenocarcinomas of the base of tongue (PABOTs), which can be further subdivided into colonic-type adenocarcinoma of the tongue and oral cavity, UGI-LA, and not otherwise specified categories, and reiterate a need for recognition and distinction of PABOT from salivary gland tumors. A subset originates from teratoid/duplication cysts, necessitating extensive sampling. Multicentric studies are essential to clinically and biologically prognosticate each of these categories.},\n\turldate = {2023-02-08},\n\tjournal = {Archives of Pathology \\& Laboratory Medicine},\n\tauthor = {Yadav, Subhash and Mittal, Neha and Rane, Swapnil U. and Bal, Munita and Patil, Asawari and Ankathi, Suman Kumar and Nair, Deepa},\n\tmonth = jan,\n\tyear = {2023},\n\tkeywords = {STS, STSplus},\n}\n\n

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\n \n\n \n \n \n \n \n \n What Have We Learned from Patients Who Have Arboleda-Tham Syndrome Due to a De Novo KAT6A Pathogenic Variant with Impaired Histone Acetyltransferase Function? A Precise Clinical Description May Be Critical for Genetic Testing Approach and Final Diagnosis.\n \n \n \n \n\n\n \n Bukvic, N.; Chetta, M.; Bagnulo, R.; Leotta, V.; Pantaleo, A.; Palumbo, O.; Palumbo, P.; Oro, M.; Rivieccio, M.; Laforgia, N.; De Rinaldis, M.; Rosati, A.; Kerkhof, J.; Sadikovic, B.; and Resta, N.\n\n\n \n\n\n\n Genes, 14(1): 165. January 2023.\n Number: 1 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"What$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{bukvic_what_2023,\n\ttitle = {What {Have} {We} {Learned} from {Patients} {Who} {Have} {Arboleda}-{Tham} {Syndrome} {Due} to a {De} {Novo} {KAT6A} {Pathogenic} {Variant} with {Impaired} {Histone} {Acetyltransferase} {Function}? {A} {Precise} {Clinical} {Description} {May} {Be} {Critical} for {Genetic} {Testing} {Approach} and {Final} {Diagnosis}},\n\tvolume = {14},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2073-4425},\n\tshorttitle = {What {Have} {We} {Learned} from {Patients} {Who} {Have} {Arboleda}-{Tham} {Syndrome} {Due} to a {De} {Novo} {KAT6A} {Pathogenic} {Variant} with {Impaired} {Histone} {Acetyltransferase} {Function}?},\n\turl = {https://www.mdpi.com/2073-4425/14/1/165},\n\tdoi = {10.3390/genes14010165},\n\tabstract = {Pathogenic variants in genes are involved in histone acetylation and deacetylation resulting in congenital anomalies, with most patients displaying a neurodevelopmental disorder and dysmorphism. Arboleda-Tham syndrome caused by pathogenic variants in KAT6A (Lysine Acetyltransferase 6A; OMIM 601408) has been recently described as a new neurodevelopmental disorder. Herein, we describe a patient characterized by complex phenotype subsequently diagnosed using the clinical exome sequencing (CES) with Arboleda-Tham syndrome (ARTHS; OMIM 616268). The analysis revealed the presence of de novo pathogenic variant in KAT6A gene, a nucleotide c.3385C{\\textgreater}T substitution that introduces a premature termination codon (p.Arg1129*). The need for straight multidisciplinary collaboration and accurate clinical description findings (bowel obstruction/megacolon/intestinal malrotation) was emphasized, together with the utility of CES in establishing an etiological basis in clinical and genetical heterogeneous conditions. Therefore, considering the phenotypic characteristics, the condition’s rarity and the reviewed literature, we propose additional diagnostic criteria that could help in the development of future clinical diagnostic guidelines. This was possible thanks to objective examinations performed during the long follow-up period, which permitted scrupulous registration of phenotypic changes over time to further assess this rare disorder. Finally, given that different genetic syndromes are associated with distinct genomic DNA methylation patterns used for diagnostic testing and/or as biomarker of disease, a specific episignature for ARTHS has been identified.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2023-02-08},\n\tjournal = {Genes},\n\tauthor = {Bukvic, Nenad and Chetta, Massimiliano and Bagnulo, Rosanna and Leotta, Valentina and Pantaleo, Antonino and Palumbo, Orazio and Palumbo, Pietro and Oro, Maria and Rivieccio, Maria and Laforgia, Nicola and De Rinaldis, Marta and Rosati, Alessandra and Kerkhof, Jennifer and Sadikovic, Bekim and Resta, Nicoletta},\n\tmonth = jan,\n\tyear = {2023},\n\tnote = {Number: 1\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {CES, DDM},\n\tpages = {165},\n}\n\n

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\n \n 2022\n \n \n (132)\n \n \n

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\n \n\n \n \n \n \n \n \n Genetic Testing for Malformations of Cortical Development: A Clinical Diagnostic Study.\n \n \n \n \n\n\n \n Straka, B.; Hermanovska, B.; Krskova, L.; Zamecnik, J.; Vlckova, M.; Balascakova, M.; Tesner, P.; Jezdik, P.; Tichy, M.; Kyncl, M.; Musilova, A.; Lassuthova, P.; Marusic, P.; Krsek, P.; and Group, o. b. o. t. M. P. S.\n\n\n \n\n\n\n Neurology Genetics, 8(5). September 2022.\n Publisher: Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology Section: Research Article\n\n\n\n
\n\n\n\n \n \n $\"Genetic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{straka_genetic_2022,\n\ttitle = {Genetic {Testing} for {Malformations} of {Cortical} {Development}: {A} {Clinical} {Diagnostic} {Study}},\n\tvolume = {8},\n\tcopyright = {Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.},\n\tissn = {2376-7839},\n\tshorttitle = {Genetic {Testing} for {Malformations} of {Cortical} {Development}},\n\turl = {https://ng.neurology.org/content/8/5/e200032},\n\tdoi = {10.1212/NXG.0000000000200032},\n\tabstract = {Background and Objectives Malformations of cortical development (MCD), though individually rare, constitute a significant burden of disease. The diagnostic yield of next-generation sequencing (NGS) in these patients varies across studies and methods, and novel genes and variants continue to emerge.\nMethods Patients (n = 123) with a definite radiologic or histopathologic diagnosis of MCD, with or without epilepsy were included in this study. They underwent NGS-based targeted gene panel (TGP) testing, whole-exome sequencing (WES), or WES-based virtual panel testing. Selected patients who underwent epilepsy surgery (n = 69) also had somatic gene testing of brain tissue–derived DNA. We analyzed predictors of positive germline genetic finding and diagnostic yield of respective methods.\nResults Pathogenic or likely pathogenic germline genetic variants were detected in 21\\% of patients (26/123). In the surgical subgroup (69/123), we performed somatic sequencing in 40\\% of cases (28/69) and detected causal variants in 18\\% (5/28). Diagnostic yield did not differ between TGP, WES-based virtual gene panel, and open WES (p = 0.69). Diagnosis of focal cortical dysplasia type 2A, epilepsy, and intellectual disability were associated with positive results of germline testing. We report previously unpublished variants in 16/26 patients and 4 cases of MCD with likely pathogenic variants in non-MCD genes.\nDiscussion In this study, we are reporting genetic findings of a large cohort of MCD patients with epilepsy or potentially epileptogenic MCD. We determine predictors of successful ascertainment of a genetic diagnosis in real-life setting and report novel, likely pathogenic variants in MCD and non-MCD genes alike.},\n\tlanguage = {en},\n\tnumber = {5},\n\turldate = {2022-12-13},\n\tjournal = {Neurology Genetics},\n\tauthor = {Straka, Barbora and Hermanovska, Barbora and Krskova, Lenka and Zamecnik, Josef and Vlckova, Marketa and Balascakova, Miroslava and Tesner, Pavel and Jezdik, Petr and Tichy, Michal and Kyncl, Martin and Musilova, Alena and Lassuthova, Petra and Marusic, Petr and Krsek, Pavel and Group, on behalf of the MCD Prague Study},\n\tmonth = sep,\n\tyear = {2022},\n\tnote = {Publisher: Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology\nSection: Research Article},\n\tkeywords = {Alamut},\n}\n\n

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\n \n\n \n \n \n \n \n \n Embryonated Chicken Tumor Xenografts Derived from Circulating Tumor Cells as a Relevant Model to Study Metastatic Dissemination: A Proof of Concept.\n \n \n \n \n\n\n \n Rousset, X.; Maillet, D.; Grolleau, E.; Barthelemy, D.; Calattini, S.; Brevet, M.; Balandier, J.; Raffin, M.; Geiguer, F.; Garcia, J.; Decaussin-Petrucci, M.; Peron, J.; Benzerdjeb, N.; Couraud, S.; Viallet, J.; and Payen, L.\n\n\n \n\n\n\n Cancers, 14(17): 4085. August 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Embryonated$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{rousset_embryonated_2022,\n\ttitle = {Embryonated {Chicken} {Tumor} {Xenografts} {Derived} from {Circulating} {Tumor} {Cells} as a {Relevant} {Model} to {Study} {Metastatic} {Dissemination}: {A} {Proof} of {Concept}},\n\tvolume = {14},\n\tissn = {2072-6694},\n\tshorttitle = {Embryonated {Chicken} {Tumor} {Xenografts} {Derived} from {Circulating} {Tumor} {Cells} as a {Relevant} {Model} to {Study} {Metastatic} {Dissemination}},\n\turl = {https://www.mdpi.com/2072-6694/14/17/4085},\n\tdoi = {10.3390/cancers14174085},\n\tabstract = {Patient-Derived Xenografts (PDXs) in the Chorioallantoic Membrane (CAM) are a representative model for studying human tumors. Circulating Tumor Cells (CTCs) are involved in cancer dissemination and treatment resistance mechanisms. To facilitate research and deep analysis of these few cells, significant efforts were made to expand them. We evaluated here whether the isolation of fresh CTCs from patients with metastatic cancers could provide a reliable tumor model after a CAM xenograft. We enrolled 35 patients, with breast, prostate, or lung metastatic cancers. We performed microfluidic-based CTC enrichment. After 48–72 h of culture, the CTCs were engrafted onto the CAM of embryonated chicken eggs at day 9 of embryonic development (EDD9). The tumors were resected 9 days after engraftment and histopathological, immunochemical, and genomic analyses were performed. We obtained in ovo tumors for 61\\% of the patients. Dedifferentiated small tumors with spindle-shaped cells were observed. The epithelial-to-mesenchymal transition of CTCs could explain this phenotype. Beyond the feasibility of NGS in this model, we have highlighted a genomic concordance between the in ovo tumor and the original patient’s tumor for constitutional polymorphism and somatic alteration in one patient. Alu DNA sequences were detected in the chicken embryo’s distant organs, supporting the idea of dedifferentiated cells with aggressive behavior. To our knowledge, we performed the first chicken CAM CTC-derived xenografts with NGS analysis and evidence of CTC dissemination in the chicken embryo.},\n\tlanguage = {en},\n\tnumber = {17},\n\turldate = {2022-11-15},\n\tjournal = {Cancers},\n\tauthor = {Rousset, Xavier and Maillet, Denis and Grolleau, Emmanuel and Barthelemy, David and Calattini, Sara and Brevet, Marie and Balandier, Julie and Raffin, Margaux and Geiguer, Florence and Garcia, Jessica and Decaussin-Petrucci, Myriam and Peron, Julien and Benzerdjeb, Nazim and Couraud, Sébastien and Viallet, Jean and Payen, Léa},\n\tmonth = aug,\n\tyear = {2022},\n\tkeywords = {CAM, CTC, Custom Cancer Panel, EDD9, NGS},\n\tpages = {4085},\n}\n\n

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\n \n\n \n \n \n \n \n \n A Novel GATA1 Variant in the C-Terminal Zinc Finger Compared with the Platelet Phenotype of Patients with A Likely Pathogenic Variant in the N-Terminal Zinc Finger.\n \n \n \n \n\n\n \n Bastida, J.; Malvestiti, S.; Boeckelmann, D.; Palma-Barqueros, V.; Wolter, M.; Lozano, M.; Glonnegger, H.; Benito, R.; Zaninetti, C.; Sobotta, F.; Schilling, F.; Morgan, N.; Freson, K.; Rivera, J.; and Zieger, B.\n\n\n \n\n\n\n Cells, 11(20): 3223. October 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{bastida_novel_2022,\n\ttitle = {A {Novel} {GATA1} {Variant} in the {C}-{Terminal} {Zinc} {Finger} {Compared} with the {Platelet} {Phenotype} of {Patients} with {A} {Likely} {Pathogenic} {Variant} in the {N}-{Terminal} {Zinc} {Finger}},\n\tvolume = {11},\n\tissn = {2073-4409},\n\turl = {https://www.mdpi.com/2073-4409/11/20/3223},\n\tdoi = {10.3390/cells11203223},\n\tabstract = {The GATA1 transcription factor is essential for normal erythropoiesis and megakaryocytic differentiation. Germline GATA1 pathogenic variants in the N-terminal zinc ﬁnger (N-ZF) are typically associated with X-linked thrombocytopenia, platelet dysfunction, and dyserythropoietic anemia. A few variants in the C-terminal ZF (C-ZF) domain are described with normal platelet count but altered platelet function as the main characteristic. Independently performed molecular genetic analysis identiﬁed a novel hemizygous variant (c.865C{\\textgreater}T, p.H289Y) in the C-ZF region of GATA1 in a German patient and in a Spanish patient. We characterized the bleeding and platelet phenotype of these patients and compared these ﬁndings with the parameters of two German siblings carrying the likely pathogenic variant p.D218N in the GATA1 N-ZF domain. The main difference was profound thrombocytopenia in the brothers carrying the p.D218N variant compared to a normal platelet count in patients carrying the p.H289Y variant; only the Spanish patient occasionally developed mild thrombocytopenia. A functional platelet defect affecting αIIbβ3 integrin activation and α-granule secretion was present in all patients. Additionally, mild anemia, anisocytosis, and poikilocytosis were observed in the patients with the C-ZF variant. Our data support the concept that GATA1 variants located in the different ZF regions can lead to clinically diverse manifestations.},\n\tlanguage = {en},\n\tnumber = {20},\n\turldate = {2023-03-09},\n\tjournal = {Cells},\n\tauthor = {Bastida, José and Malvestiti, Stefano and Boeckelmann, Doris and Palma-Barqueros, Verónica and Wolter, Mira and Lozano, María and Glonnegger, Hannah and Benito, Rocío and Zaninetti, Carlo and Sobotta, Felix and Schilling, Freimut and Morgan, Neil and Freson, Kathleen and Rivera, José and Zieger, Barbara},\n\tmonth = oct,\n\tyear = {2022},\n\tkeywords = {Alamut Visual Plus},\n\tpages = {3223},\n}\n\n

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\n \n\n \n \n \n \n \n \n Distribution of homologous recombination deficiency (HRD) and BRCA mutations (m) detected by HRD-One test among Brazilian patients (pts) with newly diagnosed advanced epithelial ovarian, fallopian tube, or peritoneal cancer.\n \n \n \n \n\n\n \n Scaranti, M.; Lopes Yamamoto, G.; Guarischi Sousa, R.; J Paniza, A. C.; Milanezi, F.; and Scapulatempo-Neto, C.\n\n\n \n\n\n\n Journal of Clinical Oncology, 40(16_suppl): e17600–e17600. June 2022.\n Publisher: Wolters Kluwer\n\n\n\n
\n\n\n\n \n \n $\"Distribution$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{scaranti_distribution_2022,\n\ttitle = {Distribution of homologous recombination deficiency ({HRD}) and {BRCA} mutations (m) detected by {HRD}-{One} test among {Brazilian} patients (pts) with newly diagnosed advanced epithelial ovarian, fallopian tube, or peritoneal cancer.},\n\tvolume = {40},\n\tissn = {0732-183X},\n\turl = {https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.e17600},\n\tdoi = {10.1200/JCO.2022.40.16_suppl.e17600},\n\tabstract = {e17600\n\nBackground: In the Phase III PAOLA-1/ENGOT-ov25 (NCT02477644) and PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) trials, the addition of a poly(ADP-ribose) polymerase (PARP) inhibitor as maintenance therapy led to a significant progression-free survival benefit in pts with newly diagnosed advanced ovarian cancer, particularly in those who were HRD positive, both including pts with BRCA1m and/or BRCA2m and pts without a BRCAm. Both trials used Myriad's myChoice to determine HRD status. However, this test is economically inaccessible for a significant fraction of the Brazilian population. Methods: We explored the prevalence and distribution of HRD and tumor (t) BRCAmin Brazilian pts using the HRD-One test that detects not only sequence variants in genes involved in homologous recombination repair (HRR) but also the genomic scars due to HRD that might be present even when a pathogenic variant in one of the HRR genes is not detected. Firstly, 59 high-grade serous epithelial ovarian cancer (HGSOC) samples were tested and the accuracy of the HRD-One score was established both by correlation with Myriad's myChoice score and an internal validation considering that most of the samples that carry a pathogenic variant in BRCA1 or BRCA2 should have HRD. HRD-One score of 2.0 or greater predicted HRD and correlated to Myriad's myChoice score of 42. HRD-One achieved an overall categorical concordance of 94.74\\% with the previously available commercial HRD test. We then tested stage III and IV HGSOC and high-grade endometrioid ovarian cancer pts’ tumor samples with HRD-One test only. Results: Of the 468 pts, 224 (47,9\\%) had HRD positive tumors, 213 (45,5\\%) were HRD negative, and 31 (6,6\\%) had inconclusive results. Ninety-six pts had tBRCAm, 95 (98.9\\%) of them had a genomic instability score compatible with HRD, and 59 (61\\%) had BRCA1m. BRCA1c.5266dupC was the most prevalent pathogenic variant in this population followed by BRCA1c.470\\_471del, c.5074+2T {\\textgreater} C, c.5251C {\\textgreater} T, and c.3331\\_3334del. The most prevalent BRCA2m were c.8488-1G {\\textgreater} A, c.5216dupA, c.5073dupA, c.1796\\_1800del, c.8351G {\\textgreater} A, c.2808\\_2811del, and c.9382C {\\textgreater} T. Median age at diagnosis was 63 in the study population, 57 in the BRCA1m, and 60 in the BRCA2m group. 47,6\\% of the HGSOC were HRD positive, whereas 25\\% of the high-grade endometrioid ovarian cancer were HRD positive. Conclusions: This is the first study to report HRD prevalence in a cohort of Brazilian pts using HRD-One test validated to detect HRD genomic scars and tBRCAm. HRD was detected in approximately 50\\% of HGSOC pts which is in line with previous studies in different populations. HRD-One might help us select pts to receive PARP inhibitors in the front-line therapy noticeably in a low-resource setting where Myriad's myChoice is not widely available.},\n\tnumber = {16\\_suppl},\n\turldate = {2022-09-28},\n\tjournal = {Journal of Clinical Oncology},\n\tauthor = {Scaranti, Mariana and Lopes Yamamoto, Guilherme and Guarischi Sousa, Rodrigo and J Paniza, Ana Carolina and Milanezi, Fernanda and Scapulatempo-Neto, Cristovam},\n\tmonth = jun,\n\tyear = {2022},\n\tnote = {Publisher: Wolters Kluwer},\n\tpages = {e17600--e17600},\n}\n\n

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\n e17600 Background: In the Phase III PAOLA-1/ENGOT-ov25 (NCT02477644) and PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) trials, the addition of a poly(ADP-ribose) polymerase (PARP) inhibitor as maintenance therapy led to a significant progression-free survival benefit in pts with newly diagnosed advanced ovarian cancer, particularly in those who were HRD positive, both including pts with BRCA1m and/or BRCA2m and pts without a BRCAm. Both trials used Myriad's myChoice to determine HRD status. However, this test is economically inaccessible for a significant fraction of the Brazilian population. Methods: We explored the prevalence and distribution of HRD and tumor (t) BRCAmin Brazilian pts using the HRD-One test that detects not only sequence variants in genes involved in homologous recombination repair (HRR) but also the genomic scars due to HRD that might be present even when a pathogenic variant in one of the HRR genes is not detected. Firstly, 59 high-grade serous epithelial ovarian cancer (HGSOC) samples were tested and the accuracy of the HRD-One score was established both by correlation with Myriad's myChoice score and an internal validation considering that most of the samples that carry a pathogenic variant in BRCA1 or BRCA2 should have HRD. HRD-One score of 2.0 or greater predicted HRD and correlated to Myriad's myChoice score of 42. HRD-One achieved an overall categorical concordance of 94.74% with the previously available commercial HRD test. We then tested stage III and IV HGSOC and high-grade endometrioid ovarian cancer pts’ tumor samples with HRD-One test only. Results: Of the 468 pts, 224 (47,9%) had HRD positive tumors, 213 (45,5%) were HRD negative, and 31 (6,6%) had inconclusive results. Ninety-six pts had tBRCAm, 95 (98.9%) of them had a genomic instability score compatible with HRD, and 59 (61%) had BRCA1m. BRCA1c.5266dupC was the most prevalent pathogenic variant in this population followed by BRCA1c.470_471del, c.5074+2T \\textgreater C, c.5251C \\textgreater T, and c.3331_3334del. The most prevalent BRCA2m were c.8488-1G \\textgreater A, c.5216dupA, c.5073dupA, c.1796_1800del, c.8351G \\textgreater A, c.2808_2811del, and c.9382C \\textgreater T. Median age at diagnosis was 63 in the study population, 57 in the BRCA1m, and 60 in the BRCA2m group. 47,6% of the HGSOC were HRD positive, whereas 25% of the high-grade endometrioid ovarian cancer were HRD positive. Conclusions: This is the first study to report HRD prevalence in a cohort of Brazilian pts using HRD-One test validated to detect HRD genomic scars and tBRCAm. HRD was detected in approximately 50% of HGSOC pts which is in line with previous studies in different populations. HRD-One might help us select pts to receive PARP inhibitors in the front-line therapy noticeably in a low-resource setting where Myriad's myChoice is not widely available.\n

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\n \n\n \n \n \n \n \n \n Radiomics Analysis on [68Ga]Ga-PSMA-11 PET and MRI-ADC for the Prediction of Prostate Cancer ISUP Grades: Preliminary Results of the BIOPSTAGE Trial.\n \n \n \n \n\n\n \n Feliciani, G.; Celli, M.; Ferroni, F.; Menghi, E.; Azzali, I.; Caroli, P.; Matteucci, F.; Barone, D.; Paganelli, G.; and Sarnelli, A.\n\n\n \n\n\n\n Cancers, 14(8): 1888. April 2022.\n Number: 8 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Radiomics$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 7 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{feliciani_radiomics_2022,\n\ttitle = {Radiomics {Analysis} on [{68Ga}]{Ga}-{PSMA}-11 {PET} and {MRI}-{ADC} for the {Prediction} of {Prostate} {Cancer} {ISUP} {Grades}: {Preliminary} {Results} of the {BIOPSTAGE} {Trial}},\n\tvolume = {14},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2072-6694},\n\tshorttitle = {Radiomics {Analysis} on [{68Ga}]{Ga}-{PSMA}-11 {PET} and {MRI}-{ADC} for the {Prediction} of {Prostate} {Cancer} {ISUP} {Grades}},\n\turl = {https://www.mdpi.com/2072-6694/14/8/1888},\n\tdoi = {10.3390/cancers14081888},\n\tabstract = {Prostate cancer (PCa) risk categorization based on clinical/PSA testing results in a substantial number of men being overdiagnosed with indolent, early-stage PCa. Clinically non-significant PCa is characterized as the presence of ISUP grade one, where PCa is found in no more than two prostate biopsy cores.MRI-ADC and [68Ga]Ga-PSMA-11 PET have been proposed as tools to predict ISUP grade one patients and consequently reduce overdiagnosis. In this study, Radiomics analysis is applied to MRI-ADC and [68Ga]Ga-PSMA-11 PET maps to quantify tumor characteristics and predict histology-proven ISUP grades. ICC was applied with a threshold of 0.6 to assess the features’ stability with variations in contouring. Logistic regression predictive models based on imaging features were trained on 31 lesions to differentiate ISUP grade one patients from ISUP two+ patients. The best model based on [68Ga]Ga-PSMA-11 PET returned a prediction efficiency of 95\\% in the training phase and 100\\% in the test phase whereas the best model based on MRI-ADC had an efficiency of 100\\% in both phases. Employing both imaging modalities, prediction efficiency was 100\\% in the training phase and 93\\% in the test phase. Although our patient cohort was small, it was possible to assess that both imaging modalities add information to the prediction models and show promising results for further investigations.},\n\tlanguage = {en},\n\tnumber = {8},\n\turldate = {2022-04-27},\n\tjournal = {Cancers},\n\tauthor = {Feliciani, Giacomo and Celli, Monica and Ferroni, Fabio and Menghi, Enrico and Azzali, Irene and Caroli, Paola and Matteucci, Federica and Barone, Domenico and Paganelli, Giovanni and Sarnelli, Anna},\n\tmonth = apr,\n\tyear = {2022},\n\tnote = {Number: 8\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Ga-PSMA-11 PET, MRI-ADC scans, prostate cancer, radiomics, retrospective studies},\n\tpages = {1888},\n}\n\n

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\n \n\n \n \n \n \n \n The Impact of Big Data Quality Analytics on Knowledge Management in Healthcare Institutions: Lessons Learned from Big Data's Application within The Healthcare Sector.\n \n \n \n\n\n \n Research, O.; Ravikumar, R.; Kitana, A.; Taamneh, A.; Aburayya, A.; Shwedeh, F.; Salloum, S.; and Shaalan, K.\n\n\n \n\n\n\n , 5: 1–17. December 2022.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{research_impact_2022,\n\ttitle = {The {Impact} of {Big} {Data} {Quality} {Analytics} on {Knowledge} {Management} in {Healthcare} {Institutions}: {Lessons} {Learned} from {Big} {Data}'s {Application} within {The} {Healthcare} {Sector}},\n\tvolume = {5},\n\tshorttitle = {The {Impact} of {Big} {Data} {Quality} {Analytics} on {Knowledge} {Management} in {Healthcare} {Institutions}},\n\tdoi = {10.11576/seejph-6194},\n\tabstract = {It is widely acknowledged that knowledge management is critical to an organization's survival and growth. Every day, higher education institutions that are considered knowledge centers generate massive volumes of data. When this data is analyzed using appropriate computational methods and technology, it can provide knowledge to improve organizational performance and students' academic experience. Healthcare organizations create massive volumes of data as a result of the usage of digital technologies to manage patient information and the organization's operations. When used successfully, this data aids in the creation of information that improves patient health and everyday organizational functioning, as well as the prevention of unfavorable public health scenarios such as the spread of infectious illnesses. This is where big data analytics comes in, providing rational methods for navigating enormous quantities of data to disclose knowledge that assists businesses and analysts in making faster and better decisions. Higher education, like healthcare, creates large amounts of heterogeneous data that hides useful knowledge. As a result, the strategies used by healthcare companies to improve their performance using big data are replicable in the education domain as well. This article examines the use of big data for knowledge management in healthcare using case studies incorporating various analytics and draws parallels to be applied in higher education. As a result, it highlights the possibility of adapting analytics technology and tools from healthcare to higher education with appropriate revisions and adaptations.},\n\tauthor = {Research, Original and Ravikumar, Rejitha and Kitana, Abdelkarim and Taamneh, Abdallah and Aburayya, Ahmad and Shwedeh, Fanar and Salloum, Said and Shaalan, Khaled},\n\tmonth = dec,\n\tyear = {2022},\n\tkeywords = {Knowledge management},\n\tpages = {1--17},\n}\n\n

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\n \n\n \n \n \n \n \n \n RUNX1 mutation has no prognostic significance in paediatric AML: A retrospective study of the AML-BFM study group.\n \n \n \n \n\n\n \n Sendker, S.; Awada, A.; Domagalla, S.; Sendker, M.; Orhan, E.; Hoffmeister, L.; Antoniou, E.; Niktoreh, N.; Reinhardt, D.; von Neuhoff, N.; and Schneider, M.\n\n\n \n\n\n\n Technical Report In Review, December 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"RUNX1$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@techreport{sendker_runx1_2022,\n\ttype = {preprint},\n\ttitle = {{RUNX1} mutation has no prognostic significance in paediatric {AML}: {A} retrospective study of the {AML}-{BFM} study group},\n\tshorttitle = {{RUNX1} mutation has no prognostic significance in paediatric {AML}},\n\turl = {https://www.researchsquare.com/article/rs-2378701/v1},\n\tabstract = {Abstract\n          \n            In acute myeloid leukaemia (AML)\n            RUNX1\n            mutation is characterized by certain clinicopathological features with poor prognosis and adverse risk by the European LeukemiaNet recommendation. Though initially considered as provisional category, the recent World Health Organization (WHO) classification of 2022 removed\n            RUNX1\n            -mutated AML from the unique entity. However, the significance of\n            RUNX1\n            mutation in paediatric AML remains unclear. We retrospectively analysed a German cohort of 488 paediatric patients with\n            de novo\n            AML, enrolled in the AMLR12 or AMLR17 registry of the AML-BFM Study Group (Essen, Germany). A total of 23 paediatric AML patients (4.7\\%) harboured\n            RUNX1\n            mutations, 18 of which (3.7\\%) had\n            RUNX1\n            mutation at initial diagnosis.\n            RUNX1\n            mutations were associated with older age, male gender, number of coexisting alterations and presence of\n            FLT3\n            -ITD but mutually exclusive of\n            KRAS\n            ,\n            KIT\n            and\n            NPM1\n            mutation.\n            RUNX1\n            mutations did not prognostically impact overall- or event-free survival. Response rates did not differ between patients with and without\n            RUNX1\n            mutations. This comprehensive study, comprising the largest analysis of RUNX1 mutation in a paediatric cohort to date, reveals distinct but not unique clinicopathologic features, with no prognostic significance of\n            RUNX1\n            -mutated paediatric AML. These results broaden the perspective on the relevance of\n            RUNX1\n            alterations in leukaemogenesis in AML.},\n\tlanguage = {en},\n\turldate = {2023-01-18},\n\tinstitution = {In Review},\n\tauthor = {Sendker, Stephanie and Awada, Amani and Domagalla, Sophia and Sendker, Michael and Orhan, Eser and Hoffmeister, Lina and Antoniou, Evangelia and Niktoreh, Naghmeh and Reinhardt, Dirk and von Neuhoff, Nils and Schneider, Markus},\n\tmonth = dec,\n\tyear = {2022},\n\tdoi = {10.21203/rs.3.rs-2378701/v1},\n\tkeywords = {DDM},\n}\n\n

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\n \n\n \n \n \n \n \n \n Germline variants associated with breast cancer in Khakass women of North Asia.\n \n \n \n \n\n\n \n Gervas, P.; Molokov, A.; Zarubin, A.; Topolnitskiy, E.; Shefer, N.; Pisareva, L.; Choynzonov, E.; and Cherdyntseva, N.\n\n\n \n\n\n\n Molecular Biology Reports. December 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Germline$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{gervas_germline_2022,\n\ttitle = {Germline variants associated with breast cancer in {Khakass} women of {North} {Asia}},\n\tissn = {1573-4978},\n\turl = {https://doi.org/10.1007/s11033-022-08215-1},\n\tdoi = {10.1007/s11033-022-08215-1},\n\tabstract = {Variants in the BRCA1/2 genes are responsible for familial breast cancer. Numerous studies showed a different spectrum of BRCA variants among breast cancer patients of different Ethnicity origin. In the available literature, no previous research has focused on breast cancer-associated variants among the Khakass people (the indigenous people of the Russian Federation).},\n\tlanguage = {en},\n\turldate = {2023-01-18},\n\tjournal = {Molecular Biology Reports},\n\tauthor = {Gervas, Polina and Molokov, Aleksey and Zarubin, Aleksei and Topolnitskiy, Evgenii and Shefer, Nikolay and Pisareva, Lubov and Choynzonov, Evgeny and Cherdyntseva, Nadezda},\n\tmonth = dec,\n\tyear = {2022},\n\tkeywords = {BRCA, HCS},\n}\n\n

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\n \n\n \n \n \n \n \n Dipartimento di Biologia e Biotecnologie.\n \n \n \n\n\n \n Molin, M. D.\n\n\n \n\n\n\n . December 2022.\n \n\n\n\n
\n\n\n\n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{molin_dipartimento_2022,\n\ttitle = {Dipartimento di {Biologia} e {Biotecnologie}},\n\tlanguage = {en},\n\tauthor = {Molin, Matteo Dal},\n\tmonth = dec,\n\tyear = {2022},\n\tkeywords = {Custom Panel, DDM, HCS},\n}\n\n

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\n \n\n \n \n \n \n \n \n AXIN2 germline testing in a French cohort validates pathogenic variants as a rare cause of predisposition to colorectal polyposis and cancer.\n \n \n \n \n\n\n \n Leclerc, J.; Beaumont, M.; Vibert, R.; Pinson, S.; Vermaut, C.; Flament, C.; Lovecchio, T.; Delattre, L.; Demay, C.; Coulet, F.; Guillerm, E.; Hamzaoui, N.; Benusiglio, P. R.; Brahimi, A.; Cornelis, F.; Delhomelle, H.; Fert-Ferrer, S.; Fournier, B. P. J.; Hovnanian, A.; Legrand, C.; Lortholary, A.; Malka, D.; Petit, F.; Saurin, J.; Lejeune, S.; Colas, C.; and Buisine, M.\n\n\n \n\n\n\n Genes, Chromosomes and Cancer, n/a(n/a). December 2022.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/gcc.23112\n\n\n\n
\n\n\n\n \n \n $\"AXIN2$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{leclerc_axin2_2022,\n\ttitle = {{AXIN2} germline testing in a {French} cohort validates pathogenic variants as a rare cause of predisposition to colorectal polyposis and cancer},\n\tvolume = {n/a},\n\tissn = {1098-2264},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/gcc.23112},\n\tdoi = {10.1002/gcc.23112},\n\tabstract = {Only a few patients with germline AXIN2 variants and colorectal adenomatous polyposis or cancer have been described, raising questions about the actual contribution of this gene to colorectal cancer (CRC) susceptibility. To assess the clinical relevance for AXIN2 testing in patients suspected of genetic predisposition to CRC, we collected clinical and molecular data from the French Oncogenetics laboratories analyzing AXIN2 in this context. Between 2004 and June 2020, 10 different pathogenic/likely pathogenic AXIN2 variants were identified in 11 unrelated individuals. Eight variants were from a consecutive series of 3322 patients, which represents a frequency of 0.24\\%. However, loss-of-function AXIN2 variants were strongly associated with genetic predisposition to CRC as compared with controls (odds ratio: 11.89, 95\\% confidence interval: 5.103–28.93). Most of the variants were predicted to produce an AXIN2 protein devoid of the SMAD3-binding and DIX domains, but preserving the β-catenin-binding domain. Ninety-one percent of the AXIN2 variant carriers who underwent colonoscopy had adenomatous polyposis. Forty percent of the variant carriers developed colorectal or/and other digestive cancer. Multiple tooth agenesis was present in at least 60\\% of them. Our report provides further evidence for a role of AXIN2 in CRC susceptibility, arguing for AXIN2 testing in patients with colorectal adenomatous polyposis or cancer.},\n\tlanguage = {en},\n\tnumber = {n/a},\n\turldate = {2023-01-18},\n\tjournal = {Genes, Chromosomes and Cancer},\n\tauthor = {Leclerc, Julie and Beaumont, Marie and Vibert, Roseline and Pinson, Stéphane and Vermaut, Catherine and Flament, Cathy and Lovecchio, Tonio and Delattre, Lucie and Demay, Christophe and Coulet, Florence and Guillerm, Erell and Hamzaoui, Nadim and Benusiglio, Patrick R. and Brahimi, Afane and Cornelis, François and Delhomelle, Hélène and Fert-Ferrer, Sandra and Fournier, Benjamin P. J. and Hovnanian, Alain and Legrand, Clémentine and Lortholary, Alain and Malka, David and Petit, Florence and Saurin, Jean-Christophe and Lejeune, Sophie and Colas, Chrystelle and Buisine, Marie-Pierre},\n\tmonth = dec,\n\tyear = {2022},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/gcc.23112},\n\tkeywords = {Alamut Visual v2.15},\n}\n\n

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\n \n\n \n \n \n \n \n \n Assessments of Somatic Variant Classification Using the Association for Molecular Pathology/American Society of Clinical Oncology/College of American Pathologists Guidelines \\textbar Elsevier Enhanced Reader.\n \n \n \n \n\n\n \n \n\n\n \n\n\n\n December 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Assessments$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@misc{noauthor_assessments_2022,\n\ttitle = {Assessments of {Somatic} {Variant} {Classification} {Using} the {Association} for {Molecular} {Pathology}/{American} {Society} of {Clinical} {Oncology}/{College} of {American} {Pathologists} {Guidelines} {\\textbar} {Elsevier} {Enhanced} {Reader}},\n\turl = {https://reader.elsevier.com/reader/sd/pii/S1525157822003397?token=A5F946CD22EFC322A399B62D413C878D7A0114463021FBFC2AB1F8D57C956EF95393A027E9784F9472AF32CA4EDE1180&originRegion=eu-west-1&originCreation=20230118080914},\n\tlanguage = {en},\n\turldate = {2023-01-18},\n\tmonth = dec,\n\tyear = {2022},\n\tdoi = {10.1016/j.jmoldx.2022.11.002},\n\tkeywords = {Alamut},\n}\n\n

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\n \n\n \n \n \n \n \n STUDY OF BINDING OF INHIBITOR MOLECULES TO THE ACTIVE SITE OF PROTEIN KINASES BY METHOD OF MOLECULAR DYNAMICS.\n \n \n \n\n\n \n Glushko, A.; Kodonidi, I.; Chiriapkin, A.; Glushko, M.; Frantsiyants, E.; and Kaplieva, I.\n\n\n \n\n\n\n CARDIOMETRY,24–26. November 2022.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{glushko_study_2022,\n\ttitle = {{STUDY} {OF} {BINDING} {OF} {INHIBITOR} {MOLECULES} {TO} {THE} {ACTIVE} {SITE} {OF} {PROTEIN} {KINASES} {BY} {METHOD} {OF} {MOLECULAR} {DYNAMICS}},\n\tdoi = {10.18137/cardiometry.2022.24.conf.11},\n\tabstract = {Eukaryotic protein kinases are represented by a large superfamily of homologous proteins similar in structure of the catalytic (kinase) domain, consisting of 250–300 amino acids [3]. Most human protein kinases share a common fold consisting of an N-terminal lobe, consisting of a five-stranded β-sheet with an α-helix called the C-helix, and a C-terminal lobe comprising six α-helices.},\n\tjournal = {CARDIOMETRY},\n\tauthor = {Glushko, A.A. and Kodonidi, I.P. and Chiriapkin, Alexey and Glushko, M.P. and Frantsiyants, Elena and Kaplieva, I.V.},\n\tmonth = nov,\n\tyear = {2022},\n\tkeywords = {HCS},\n\tpages = {24--26},\n}\n\n

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\n \n\n \n \n \n \n \n \n Real-Life Comparative Analysis of Prognostic Risk Classification According to ELN 2010, 2017 and 2022 in AML Patients.\n \n \n \n \n\n\n \n Aparicio Pérez, C.; Gonzalez Teomiro, A. C.; Martinez Losada, M. C.; Yébenes Ramírez, M.; Martin Calvo, C.; Prados de La Torre, E.; Sánchez-Garcia, J.; and Serrano, J.\n\n\n \n\n\n\n Blood, 140(Supplement 1): 9136–9137. November 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Real-Life$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{aparicio_perez_real-life_2022,\n\ttitle = {Real-{Life} {Comparative} {Analysis} of {Prognostic} {Risk} {Classification} {According} to {ELN} 2010, 2017 and 2022 in {AML} {Patients}},\n\tvolume = {140},\n\tissn = {0006-4971},\n\turl = {https://doi.org/10.1182/blood-2022-163617},\n\tdoi = {10.1182/blood-2022-163617},\n\tnumber = {Supplement 1},\n\turldate = {2023-01-18},\n\tjournal = {Blood},\n\tauthor = {Aparicio Pérez, Clara and Gonzalez Teomiro, Ana Camila and Martinez Losada, Maria Carmen and Yébenes Ramírez, Manuel and Martin Calvo, Carmen and Prados de La Torre, Esther and Sánchez-Garcia, Joaquín and Serrano, Josefina},\n\tmonth = nov,\n\tyear = {2022},\n\tkeywords = {DDM, MYS},\n\tpages = {9136--9137},\n}\n\n

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\n \n\n \n \n \n \n \n \n Novel Intronic Mutation in VMA21 Causing Severe Phenotype of X-Linked Myopathy with Excessive Autophagy—Case Report.\n \n \n \n \n\n\n \n Pegat, A.; Streichenberger, N.; Lacoste, N.; Hermier, M.; Menassa, R.; Coudert, L.; Theuriet, J.; Froissart, R.; Terrone, S.; Bouhour, F.; Michel-Calemard, L.; Schaeffer, L.; and Jacquier, A.\n\n\n \n\n\n\n Genes, 13(12): 2245. November 2022.\n Number: 12 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Novel$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{pegat_novel_2022,\n\ttitle = {Novel {Intronic} {Mutation} in {VMA21} {Causing} {Severe} {Phenotype} of {X}-{Linked} {Myopathy} with {Excessive} {Autophagy}—{Case} {Report}},\n\tvolume = {13},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2073-4425},\n\turl = {https://www.mdpi.com/2073-4425/13/12/2245},\n\tdoi = {10.3390/genes13122245},\n\tabstract = {X-linked Myopathy with Excessive Autophagy (XMEA) is a rare autophagic vacuolar myopathy caused by mutations in the Vacuolar ATPase assembly factor VMA21 gene; onset usually occurs during childhood and rarely occurs during adulthood. We described a 22-year-old patient with XMEA, whose onset was declared at 11 through gait disorder. He had severe four-limb proximal weakness and amyotrophy, and his proximal muscle MRC score was between 2 and 3/5 in four limbs; creatine kinase levels were elevated (1385 IU/L), and electroneuromyography and muscle MRI were suggestive of myopathy. Muscle biopsy showed abnormalities typical of autophagic vacuolar myopathy. We detected a hemizygous, unreported, intronic, single-nucleotide substitution c.164-20T{\\textgreater}A (NM\\_001017980.4) in intron 2 of the VMA21 gene. Fibroblasts derived from this patient displayed a reduced level of VMA21 transcripts (at 40\\% of normal) and protein, suggesting a pathogenicity related to an alteration of the splicing efficiency associated with an intron retention. This patient with XMEA displayed a severe phenotype (rapid weakness of upper and lower limbs) due to a new intronic variant of VMA21, related to an alteration in the splicing efficiency associated with intron retention, suggesting that phenotype severity is closely related to the residual expression of the VMA21 protein.},\n\tlanguage = {en},\n\tnumber = {12},\n\turldate = {2022-12-13},\n\tjournal = {Genes},\n\tauthor = {Pegat, Antoine and Streichenberger, Nathalie and Lacoste, Nicolas and Hermier, Marc and Menassa, Rita and Coudert, Laurent and Theuriet, Julian and Froissart, Roseline and Terrone, Sophie and Bouhour, Francoise and Michel-Calemard, Laurence and Schaeffer, Laurent and Jacquier, Arnaud},\n\tmonth = nov,\n\tyear = {2022},\n\tnote = {Number: 12\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Alamut Visual Plus v1.6.1, VMA21, XMEA},\n\tpages = {2245},\n}\n\n

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\n \n\n \n \n \n \n \n \n Training and Validation Cohorts for Predicting the Impact of High Molecular Risk Mutations after Allogeneic Stem Cell Transplantation in Myelofibrosis.\n \n \n \n \n\n\n \n Finazzi, M. C.; Civini, A.; Pavoni, C.; Grassi, A.; Mico', M. C.; Algarotti, A.; Bellini, M.; Patriarca, F.; Guglielmelli, P.; Luppi, M.; Rumi, E.; Polverelli, N.; Messina, G.; Bregante, S.; Milone, G.; Imovilli, A.; Bruno, B.; Musso, M.; Santarone, S.; Pini, M.; Pennisi, M.; Spinelli, O.; Bonifazi, F.; Rambaldi, A.; and Salmoiraghi, S.\n\n\n \n\n\n\n Blood, 140(Supplement 1): 10622–10623. November 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Training$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{finazzi_training_2022,\n\ttitle = {Training and {Validation} {Cohorts} for {Predicting} the {Impact} of {High} {Molecular} {Risk} {Mutations} after {Allogeneic} {Stem} {Cell} {Transplantation} in {Myelofibrosis}},\n\tvolume = {140},\n\tissn = {0006-4971},\n\turl = {https://doi.org/10.1182/blood-2022-162298},\n\tdoi = {10.1182/blood-2022-162298},\n\tnumber = {Supplement 1},\n\turldate = {2022-12-13},\n\tjournal = {Blood},\n\tauthor = {Finazzi, Maria Chiara and Civini, Alessia and Pavoni, Chiara and Grassi, Anna and Mico', Maria Caterina and Algarotti, Alessandra and Bellini, Marta and Patriarca, Francesca and Guglielmelli, Paola and Luppi, Mario and Rumi, Elisa and Polverelli, Nicola and Messina, Giuseppe and Bregante, Stefania and Milone, Giuseppe and Imovilli, Annalisa and Bruno, Benedetto and Musso, Maurizio and Santarone, Stella and Pini, Massimo and Pennisi, Martina and Spinelli, Orietta and Bonifazi, Francesca and Rambaldi, Alessandro and Salmoiraghi, Silvia},\n\tmonth = nov,\n\tyear = {2022},\n\tkeywords = {Illumina, Illumina MiniSeq platform, MYS},\n\tpages = {10622--10623},\n}\n\n

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\n \n\n \n \n \n \n \n \n Preferential Use of Coagulation Pathways Differs between Classical Myeloproliferative Neoplasms: Results of Global Coagulation Assays with Respect to Clinical and Genetic Features.\n \n \n \n \n\n\n \n Lucchesi, A.; Napolitano, R.; Bochicchio, M. T.; Simonetti, G.; Micucci, G.; Poggiaspalla, M.; Di Battista, V.; Musuraca, G.; Martinelli, G.; Giordano, G.; Foca, F.; Catani, L.; and Napolitano, M.\n\n\n \n\n\n\n Blood, 140(Supplement 1): 12160–12161. November 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Preferential$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{lucchesi_preferential_2022,\n\ttitle = {Preferential {Use} of {Coagulation} {Pathways} {Differs} between {Classical} {Myeloproliferative} {Neoplasms}: {Results} of {Global} {Coagulation} {Assays} with {Respect} to {Clinical} and {Genetic} {Features}},\n\tvolume = {140},\n\tissn = {0006-4971},\n\tshorttitle = {Preferential {Use} of {Coagulation} {Pathways} {Differs} between {Classical} {Myeloproliferative} {Neoplasms}},\n\turl = {https://doi.org/10.1182/blood-2022-171095},\n\tdoi = {10.1182/blood-2022-171095},\n\tnumber = {Supplement 1},\n\turldate = {2022-12-13},\n\tjournal = {Blood},\n\tauthor = {Lucchesi, Alessandro and Napolitano, Roberta and Bochicchio, Maria Teresa and Simonetti, Giorgia and Micucci, Giorgia and Poggiaspalla, Monica and Di Battista, Valeria and Musuraca, Gerardo and Martinelli, Giovanni and Giordano, Giulio and Foca, Flavia and Catani, Lucia and Napolitano, Mariasanta},\n\tmonth = nov,\n\tyear = {2022},\n\tkeywords = {ASA, MPN, MYS},\n\tpages = {12160--12161},\n}\n\n

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\n \n\n \n \n \n \n \n \n NGS Testing Practices and Molecular Profile Landscape of the KIT Gene in Systemic Mastocytosis: Real-World Insights from Selected European Countries.\n \n \n \n \n\n\n \n Lamontagne, N.; Cheloni, S.; Lima, S.; Cettou, G.; Green, T.; Crouch, Z.; and Kim, A.\n\n\n \n\n\n\n Blood, 140(Supplement 1): 2603–2604. November 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"NGS$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{lamontagne_ngs_2022,\n\ttitle = {{NGS} {Testing} {Practices} and {Molecular} {Profile} {Landscape} of the {KIT} {Gene} in {Systemic} {Mastocytosis}: {Real}-{World} {Insights} from {Selected} {European} {Countries}},\n\tvolume = {140},\n\tissn = {0006-4971},\n\tshorttitle = {{NGS} {Testing} {Practices} and {Molecular} {Profile} {Landscape} of the {KIT} {Gene} in {Systemic} {Mastocytosis}},\n\turl = {https://doi.org/10.1182/blood-2022-163168},\n\tdoi = {10.1182/blood-2022-163168},\n\tnumber = {Supplement 1},\n\turldate = {2022-12-13},\n\tjournal = {Blood},\n\tauthor = {Lamontagne, Nicolas and Cheloni, Stefano and Lima, Sofia and Cettou, Guillaume and Green, Teresa and Crouch, Zach and Kim, Andrew},\n\tmonth = nov,\n\tyear = {2022},\n\tkeywords = {DDM, NGS},\n\tpages = {2603--2604},\n}\n\n

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\n \n\n \n \n \n \n \n \n From Samples to Germline and Somatic Sequence Variation: A Focus on Next-Generation Sequencing in Melanoma Research.\n \n \n \n \n\n\n \n Muñoz-Barrera, A.; Rubio-Rodríguez, L. A.; Díaz-de Usera, A.; Jáspez, D.; Lorenzo-Salazar, J. M.; González-Montelongo, R.; García-Olivares, V.; and Flores, C.\n\n\n \n\n\n\n Life, 12(11): 1939. November 2022.\n Number: 11 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"From$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{munoz-barrera_samples_2022,\n\ttitle = {From {Samples} to {Germline} and {Somatic} {Sequence} {Variation}: {A} {Focus} on {Next}-{Generation} {Sequencing} in {Melanoma} {Research}},\n\tvolume = {12},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2075-1729},\n\tshorttitle = {From {Samples} to {Germline} and {Somatic} {Sequence} {Variation}},\n\turl = {https://www.mdpi.com/2075-1729/12/11/1939},\n\tdoi = {10.3390/life12111939},\n\tabstract = {Next-generation sequencing (NGS) applications have flourished in the last decade, permitting the identification of cancer driver genes and profoundly expanding the possibilities of genomic studies of cancer, including melanoma. Here we aimed to present a technical review across many of the methodological approaches brought by the use of NGS applications with a focus on assessing germline and somatic sequence variation. We provide cautionary notes and discuss key technical details involved in library preparation, the most common problems with the samples, and guidance to circumvent them. We also provide an overview of the sequence-based methods for cancer genomics, exposing the pros and cons of targeted sequencing vs. exome or whole-genome sequencing (WGS), the fundamentals of the most common commercial platforms, and a comparison of throughputs and key applications. Details of the steps and the main software involved in the bioinformatics processing of the sequencing results, from preprocessing to variant prioritization and filtering, are also provided in the context of the full spectrum of genetic variation (SNVs, indels, CNVs, structural variation, and gene fusions). Finally, we put the emphasis on selected bioinformatic pipelines behind (a) short-read WGS identification of small germline and somatic variants, (b) detection of gene fusions from transcriptomes, and (c) de novo assembly of genomes from long-read WGS data. Overall, we provide comprehensive guidance across the main methodological procedures involved in obtaining sequencing results for the most common short- and long-read NGS platforms, highlighting key applications in melanoma research.},\n\tlanguage = {en},\n\tnumber = {11},\n\turldate = {2022-12-13},\n\tjournal = {Life},\n\tauthor = {Muñoz-Barrera, Adrián and Rubio-Rodríguez, Luis A. and Díaz-de Usera, Ana and Jáspez, David and Lorenzo-Salazar, José M. and González-Montelongo, Rafaela and García-Olivares, Víctor and Flores, Carlos},\n\tmonth = nov,\n\tyear = {2022},\n\tnote = {Number: 11\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {HCS, NGS, WGS, melanoma},\n\tpages = {1939},\n}\n\n

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\n \n\n \n \n \n \n \n \n Two-Period Study Results from a Large Italian Hospital Laboratory Attesting SARS-CoV-2 Variant PCR Assay Evolution.\n \n \n \n \n\n\n \n Liotti, F. M.; De Maio, F.; Ippoliti, C.; Santarelli, G.; Monzo, F. R.; Sali, M.; Santangelo, R.; Ceccherini-Silberstein, F.; Sanguinetti, M.; and Posteraro, B.\n\n\n \n\n\n\n Microbiology Spectrum,e02922–22. November 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Two-Period$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{liotti_two-period_2022,\n\ttitle = {Two-{Period} {Study} {Results} from a {Large} {Italian} {Hospital} {Laboratory} {Attesting} {SARS}-{CoV}-2 {Variant} {PCR} {Assay} {Evolution}},\n\tissn = {2165-0497},\n\turl = {https://journals.asm.org/doi/10.1128/spectrum.02922-22},\n\tdoi = {10.1128/spectrum.02922-22},\n\tabstract = {In keeping with the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the COVID-19 causative agent, PCR assays have been developed to rapidly detect SARS-CoV-2 variants, which have emerged since the ﬁrst (Alpha) variant was identiﬁed. Based on speciﬁc assortment of SARS-CoV-2 spike-protein mutations (DH69/V70, E484K, N501Y, W152C, L452R, K417N, and K417T) among the major variants known to date, Seegene Allplex SARS-CoV-2 Variants I and Variants II assays have been available since a few months before the last (Omicron) variant became predominant. Using S gene next-generation sequencing (NGS) as the SARS-CoV-2 variant identiﬁcation reference method, we assessed the results of SARS-CoV-2-positive nasopharyngeal swab samples from two testing periods, before (n = 288, using only Variants I) and after (n = 77, using both Variants I and Variants II) the appearance of Omicron. The Variants I assay allowed correct identiﬁcation for Alpha (37/37), Beta/Gamma (28/ 30), or Delta (220/221) variant-positive samples. The combination of the Variants I and Variants II assays allowed correct identiﬁcation for 61/77 Omicron variant-positive samples. While 16 samples had the K417N mutation undetected with the Variants II assay, 74/77 samples had both DH69/V70 and N501Y mutations detected with the Variants I assay. If considering only the results by the Variants I assay, 6 (2 Beta variant positive, 1 Delta variant positive, and 3 Omicron variant positive) of 365 samples tested in total provided incorrect identiﬁcation. We showed that the Variants I assay alone might be more suitable than both the Variants I and Variants II assays to identify currently circulating SARS-CoV-2 variants. Inclusion of additional variant-speciﬁc mutations should be expected in the development of future assays.},\n\tlanguage = {en},\n\turldate = {2022-12-13},\n\tjournal = {Microbiology Spectrum},\n\tauthor = {Liotti, Flora Marzia and De Maio, Flavio and Ippoliti, Chiara and Santarelli, Giulia and Monzo, Francesca Romana and Sali, Michela and Santangelo, Rosaria and Ceccherini-Silberstein, Francesca and Sanguinetti, Maurizio and Posteraro, Brunella},\n\teditor = {Mostafa, Heba H.},\n\tcollaborator = {Dikdan, Ryan and Eldesouki, Raghda},\n\tmonth = nov,\n\tyear = {2022},\n\tkeywords = {COVID 19, DDM, SARS-CoV-2},\n\tpages = {e02922--22},\n}\n\n

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\n \n\n \n \n \n \n \n \n Application of multicolour reflectance imaging for the characterisation of inherited retinal disorders.\n \n \n \n \n\n\n \n Lorenzana-Blanco, N.; Jimenez-Rolando, B.; Garcia-Sandoval, B.; Blanco-Kelly, F.; Avila-Fernandez, A.; Martin-Merida, I.; Garcia-Ferreira, M.; Campos-Seco, S.; Ayuso, C.; and Carreño, E.\n\n\n \n\n\n\n European Journal of Ophthalmology,11206721221138891. November 2022.\n Publisher: SAGE Publications\n\n\n\n
\n\n\n\n \n \n $\"Application$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{lorenzana-blanco_application_2022,\n\ttitle = {Application of multicolour reflectance imaging for the characterisation of inherited retinal disorders},\n\tissn = {1120-6721},\n\turl = {https://doi.org/10.1177/11206721221138891},\n\tdoi = {10.1177/11206721221138891},\n\tabstract = {AimTo describe the role of multicolour reflectance images (MCI) in the phenotypic diagnosis of inherited retinal disorders (IRDs).MethodsA retrospective review of consecutive patients affected by IRDs examined with MCI techniques from January to December 2019 at a tertiary care referral centre. All patients had MCI, fundus autofluorescence and optical coherence tomography taken at the same time point. The ability of each modality to highlight clinical features was assessed. Lesions? size was also measured and compared among imaging modalities.ResultsThirty eyes of 15 patients were included in the study, 6 males and 9 females, with a mean age of 44 years (range: 19?57.5). The most frequent clinical diagnosis were: pattern dystrophies, and late-onset retinal degeneration. Next-generation or Sanger sequencing analysis was carried out in all patients. Blue and green reflectance were relevant in highlighting peripheral mottling in fundus albipunctatus, pseudoreticular drusen in late-onset retinal degeneration, parafoveal hyperreflective area in bull's eye maculopathy and crystals in Bietti's crystalline dystrophy. Likewise, it is to mention the ability of infrared reflectance to detect hyperreflective patches in posterior pole in neurofibromatosis type 1 and retinal changes in pattern dystrophies and cone dystrophies.ConclusionMulticolour imaging technique enables the detection of clinical features that could be overlooked by other imaging modalities, allowing accurate phenotypic characterisation of IRDs and guiding genetic diagnose, and may become a meaningful monitoring tool for future treatments.},\n\tlanguage = {en},\n\turldate = {2022-12-13},\n\tjournal = {European Journal of Ophthalmology},\n\tauthor = {Lorenzana-Blanco, Natalia and Jimenez-Rolando, Belen and Garcia-Sandoval, Blanca and Blanco-Kelly, Fiona and Avila-Fernandez, Almudena and Martin-Merida, Inmaculada and Garcia-Ferreira, Milagros and Campos-Seco, Silvia and Ayuso, Carmen and Carreño, Ester},\n\tmonth = nov,\n\tyear = {2022},\n\tnote = {Publisher: SAGE Publications},\n\tkeywords = {CES, IRD, MCI},\n\tpages = {11206721221138891},\n}\n\n

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\n \n\n \n \n \n \n \n \n A Novel GCK Large Genomic Rearrangement in a Patient with MODY-2 Detected by Clinical Exome Sequencing.\n \n \n \n \n\n\n \n Concolino, P.; Tartaglione, L.; De Paolis, E.; Carrozza, C.; Urbani, A.; Minucci, A.; Pitocco, D.; and Santonocito, C.\n\n\n \n\n\n\n Genes, 13(11): 2104. November 2022.\n Number: 11 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{concolino_novel_2022,\n\ttitle = {A {Novel} {GCK} {Large} {Genomic} {Rearrangement} in a {Patient} with {MODY}-2 {Detected} by {Clinical} {Exome} {Sequencing}},\n\tvolume = {13},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2073-4425},\n\turl = {https://www.mdpi.com/2073-4425/13/11/2104},\n\tdoi = {10.3390/genes13112104},\n\tabstract = {Maturity-onset diabetes of the young (MODY) is a rare form of non-autoimmune diabetes with an autosomal dominant inheritance. To date, 14 genes have been reported as genetic basis of MODY. GCK gene, encoding the glucokinase enzyme, was the first MODY gene to be identified. GCK heterozygous inactivating variants cause the GCK-MODY or MODY2 subtype. However, partial or whole gene deletions have been rarely identified, showing it to be a rare cause of GCK-MODY. We reported the molecular evaluation of a Ukrainian patient with clinical diagnosis of MODY2. We performed the Next generation sequencing of the clinical exome using the Clinical Exome Solution® kit (SOPHiA Genetics), followed by the design of a 14 genes virtual panel related to the suggestive diagnosis of MODY. Bioinformatics analysis was performed using the SOPHiA DDM platform (SOPHiA Genetics). The SALSA MLPA kit for MODY (MRC-Holland) was used for relative quantification of GCK exons. From the molecular evaluation, no pathogenic sequence variants were detected in the investigated genes. Copy Number Variation analysis was able to identify a large deletion involving the last three exons of the GCK gene. This result was confirmed by MLPA. To the best of our knowledge, the identified rearrangement has never been reported in the literature.},\n\tlanguage = {en},\n\tnumber = {11},\n\turldate = {2022-12-13},\n\tjournal = {Genes},\n\tauthor = {Concolino, Paola and Tartaglione, Linda and De Paolis, Elisa and Carrozza, Cinzia and Urbani, Andrea and Minucci, Angelo and Pitocco, Dario and Santonocito, Concetta},\n\tmonth = nov,\n\tyear = {2022},\n\tnote = {Number: 11\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {CES v2, CNV, DDM, GCK, MLPA, MODY, MODY2},\n\tpages = {2104},\n}\n\n

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\n \n\n \n \n \n \n \n \n Five years’ experience of the clinical exome sequencing in a Spanish single center.\n \n \n \n \n\n\n \n Arteche-López, A.; Ávila-Fernández, A.; Riveiro Álvarez, R.; Almoguera, B.; Bustamante Aragonés, A.; Martin-Merida, I.; López Martínez, M. A.; Giménez Pardo, A.; Vélez-Monsalve, C.; Gallego Merlo, J.; García Vara, I.; Blanco-Kelly, F.; Tahsin Swafiri, S.; Lorda Sánchez, I.; Trujillo Tiebas, M. J.; and Ayuso, C.\n\n\n \n\n\n\n Scientific Reports, 12(1): 19209. November 2022.\n Number: 1 Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"Five$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{arteche-lopez_five_2022,\n\ttitle = {Five years’ experience of the clinical exome sequencing in a {Spanish} single center},\n\tvolume = {12},\n\tcopyright = {2022 The Author(s)},\n\tissn = {2045-2322},\n\turl = {https://www.nature.com/articles/s41598-022-23786-6},\n\tdoi = {10.1038/s41598-022-23786-6},\n\tabstract = {Nowadays, exome sequencing is a robust and cost-efficient genetic diagnostic tool already implemented in many clinical laboratories. Despite it has undoubtedly improved our diagnostic capacity and has allowed the discovery of many new Mendelian-disease genes, it only provides a molecular diagnosis in up to 25–30\\% of cases. Here, we comprehensively evaluate the results of a large sample set of 4974 clinical exomes performed in our laboratory over a period of 5 years, showing a global diagnostic rate of 24.62\\% (1391/4974). For the evaluation we establish different groups of diseases and demonstrate how the diagnostic rate is not only dependent on the analyzed group of diseases (43.12\\% in ophthalmological cases vs 16.61\\% in neurological cases) but on the specific disorder (47.49\\% in retinal dystrophies vs 24.02\\% in optic atrophy; 18.88\\% in neuropathies/paraparesias vs 11.43\\% in dementias). We also detail the most frequent mutated genes within each group of disorders and discuss, on our experience, further investigations and directions needed for the benefit of patients.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2022-12-13},\n\tjournal = {Scientific Reports},\n\tauthor = {Arteche-López, A. and Ávila-Fernández, A. and Riveiro Álvarez, R. and Almoguera, B. and Bustamante Aragonés, A. and Martin-Merida, I. and López Martínez, M. A. and Giménez Pardo, A. and Vélez-Monsalve, C. and Gallego Merlo, J. and García Vara, I. and Blanco-Kelly, F. and Tahsin Swafiri, S. and Lorda Sánchez, I. and Trujillo Tiebas, M. J. and Ayuso, C.},\n\tmonth = nov,\n\tyear = {2022},\n\tnote = {Number: 1\nPublisher: Nature Publishing Group},\n\tkeywords = {CES, DDM, exome sequencing},\n\tpages = {19209},\n}\n\n

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\n \n\n \n \n \n \n \n \n Novel IGFALS mutations with predicted pathogenetic effects by the analysis of AlphaFold structure.\n \n \n \n \n\n\n \n Franzoni, A.; Baldan, F.; Passon, N.; Mio, C.; Driul, D.; Cogo, P.; Fogolari, F.; D’Aurizio, F.; and Damante, G.\n\n\n \n\n\n\n Endocrine. November 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Novel$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{franzoni_novel_2022,\n\ttitle = {Novel {IGFALS} mutations with predicted pathogenetic effects by the analysis of {AlphaFold} structure},\n\tissn = {1559-0100},\n\turl = {https://doi.org/10.1007/s12020-022-03244-z},\n\tdoi = {10.1007/s12020-022-03244-z},\n\tabstract = {According to the American College of Medical Genetics (ACMG) classification, variants of uncertain significance (VUS) are gene variations whose impact on the disease risk is not yet known. VUS, therefore, represent an unmet need for genetic counselling. Aim of the study is the use the AlphaFold artificial intelligence algorithm to predict the impact of novel mutations of the IGFALS gene, detected in a subject with short stature and initially classified as VUS according to the ACMG classification.},\n\tlanguage = {en},\n\turldate = {2022-12-13},\n\tjournal = {Endocrine},\n\tauthor = {Franzoni, Alessandra and Baldan, Federica and Passon, Nadia and Mio, Catia and Driul, Daniela and Cogo, Paola and Fogolari, Federico and D’Aurizio, Federica and Damante, Giuseppe},\n\tmonth = nov,\n\tyear = {2022},\n\tkeywords = {CES, DDM, IGFALS, WES},\n}\n\n

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\n \n\n \n \n \n \n \n \n Addison’s disease without hyperpigmentation in pediatrics: pointing towards specific causes.\n \n \n \n \n\n\n \n Giannakopoulos, A.; Sertedaki, A.; Efthymiadou, A.; and Chrysis, D.\n\n\n \n\n\n\n Hormones. November 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Addison’s$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{giannakopoulos_addisons_2022,\n\ttitle = {Addison’s disease without hyperpigmentation in pediatrics: pointing towards specific causes},\n\tissn = {2520-8721},\n\tshorttitle = {Addison’s disease without hyperpigmentation in pediatrics},\n\turl = {https://doi.org/10.1007/s42000-022-00415-5},\n\tdoi = {10.1007/s42000-022-00415-5},\n\tabstract = {Hyperpigmentation of skin and mucous membranes comprises a hallmark of the clinical diagnosis of Addison’s disease. However, there have been reports of patients with adrenal insufficiency from diverse causes who did not develop hyperpigmentation. The pathophysiology responsible for the absence of increased pigmentation is not clearly defined in many cases.},\n\tlanguage = {en},\n\turldate = {2022-12-13},\n\tjournal = {Hormones},\n\tauthor = {Giannakopoulos, Aristeidis and Sertedaki, Amalia and Efthymiadou, Alexandra and Chrysis, Dionisios},\n\tmonth = nov,\n\tyear = {2022},\n\tkeywords = {DDM, Human Core Exome Kit, SGPL1},\n}\n\n

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\n \n\n \n \n \n \n \n \n Lymphedema as first clinical presentation of Cantu Syndrome: reversed phenotyping after identification of gain-of-function variant in ABCC9.\n \n \n \n \n\n\n \n Gao, J.; McClenaghan, C.; Christiaans, I.; Alders, M.; van Duinen, K.; van Haelst, M. M.; van Haaften, G.; and Nichols, C. G.\n\n\n \n\n\n\n European Journal of Human Genetics,1–7. November 2022.\n Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"Lymphedema$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{gao_lymphedema_2022,\n\ttitle = {Lymphedema as first clinical presentation of {Cantu} {Syndrome}: reversed phenotyping after identification of gain-of-function variant in {ABCC9}},\n\tcopyright = {2022 The Author(s), under exclusive licence to European Society of Human Genetics},\n\tissn = {1476-5438},\n\tshorttitle = {Lymphedema as first clinical presentation of {Cantu} {Syndrome}},\n\turl = {https://www.nature.com/articles/s41431-022-01210-x},\n\tdoi = {10.1038/s41431-022-01210-x},\n\tabstract = {Cantu Syndrome (CS), [OMIM \\#239850] is characterized by hypertrichosis, osteochondrodysplasia, and cardiomegaly. CS is caused by gain-of-function (GOF) variants in the KCNJ8 or ABCC9 genes that encode pore-forming Kir6.1 and regulatory SUR2 subunits of ATP-sensitive potassium (KATP) channels. Many subjects with CS also present with the complication of lymphedema. A previously uncharacterized, heterozygous ABCC9 variant, p.(Leu1055\\_Glu1058delinsPro), termed indel1055, was identified in an individual diagnosed with idiopathic lymphedema. The variant was introduced into the equivalent position of rat SUR2A, and inside-out patches were used to characterize the KATP channels formed by Kir6.2 and WT or mutant SUR2A subunits coexpressed in Cosm6 cells. The indel1055 variant causes gain-of-function of the channel, with an increase of the IC50 for ATP inhibition compared to WT. Retrospective consideration of this individual reveals clear features of Cantu Syndrome. An additional heterozygous ABCC9 variant, p.(Ile419Thr), was identified in a second individual diagnosed with lymphedema. In this case, there were no additional features consistent with CS, and the properties of p.(Ile416Thr) (the corresponding mutation in rat SUR2A)--containing channels were not different from WT. This proof-of-principle study shows that idiopathic lymphedema may actually be a first presentation of otherwise unrecognized Cantu Syndrome, but molecular phenotyping of identified variants is necessary to confirm relevance.},\n\tlanguage = {en},\n\turldate = {2022-12-13},\n\tjournal = {European Journal of Human Genetics},\n\tauthor = {Gao, Jian and McClenaghan, Conor and Christiaans, Imke and Alders, Marielle and van Duinen, Kirsten and van Haelst, Mieke M. and van Haaften, Gijs and Nichols, Colin G.},\n\tmonth = nov,\n\tyear = {2022},\n\tnote = {Publisher: Nature Publishing Group},\n\tkeywords = {Alamut},\n\tpages = {1--7},\n}\n\n

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\n \n\n \n \n \n \n \n \n Canonical and uncanonical pathogenic germline variants in colorectal cancer patients by next-generation sequencing in a European referral center.\n \n \n \n \n\n\n \n Poliani, L.; Greco, L.; Barile, M.; Buono, A. D.; Bianchi, P.; Basso, G.; Giatti, V.; Genuardi, M.; Malesci, A.; and Laghi, L.\n\n\n \n\n\n\n ESMO Open, 7(6). November 2022.\n Publisher: Elsevier\n\n\n\n
\n\n\n\n \n \n $\"Canonical$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{poliani_canonical_2022,\n\ttitle = {Canonical and uncanonical pathogenic germline variants in colorectal cancer patients by next-generation sequencing in a {European} referral center},\n\tvolume = {7},\n\tissn = {2059-7029},\n\turl = {https://www.esmoopen.com/article/S2059-7029(22)00237-X/fulltext},\n\tdoi = {10.1016/j.esmoop.2022.100607},\n\tlanguage = {English},\n\tnumber = {6},\n\turldate = {2022-12-13},\n\tjournal = {ESMO Open},\n\tauthor = {Poliani, L. and Greco, L. and Barile, M. and Buono, A. Dal and Bianchi, P. and Basso, G. and Giatti, V. and Genuardi, M. and Malesci, A. and Laghi, L.},\n\tmonth = nov,\n\tyear = {2022},\n\tpmid = {36356413},\n\tnote = {Publisher: Elsevier},\n\tkeywords = {DDM, NGS},\n}\n\n

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\n \n\n \n \n \n \n \n \n Laboratory Cross-Comparison and Ring Test Trial for Tumor BRCA Testing in a Multicenter Epithelial Ovarian Cancer Series: The BORNEO GEICO 60-0 Study.\n \n \n \n \n\n\n \n Garcia-Casado, Z.; Oaknin, A.; Mendiola, M.; Alkorta-Aranburu, G.; Antunez-Lopez, J. R.; Moreno-Bueno, G.; Palacios, J.; Yubero, A.; Marquez, R.; Gallego, A.; Sanchez-Heras, A. B.; Lopez-Guerrero, J. A.; Perez-Segura, C.; Barretina-Ginesta, P.; Alarcon, J.; Gaba, L.; Marquez, A.; Matito, J.; Cueva, J.; Palacio, I.; Iglesias, M.; Arcusa, A.; Sanchez-Lorenzo, L.; Guerra-Alia, E.; Romero, I.; and Vivancos, A.\n\n\n \n\n\n\n Journal of Personalized Medicine, 12(11): 1842. November 2022.\n Number: 11 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Laboratory$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{garcia-casado_laboratory_2022,\n\ttitle = {Laboratory {Cross}-{Comparison} and {Ring} {Test} {Trial} for {Tumor} {BRCA} {Testing} in a {Multicenter} {Epithelial} {Ovarian} {Cancer} {Series}: {The} {BORNEO} {GEICO} 60-0 {Study}},\n\tvolume = {12},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2075-4426},\n\tshorttitle = {Laboratory {Cross}-{Comparison} and {Ring} {Test} {Trial} for {Tumor} {BRCA} {Testing} in a {Multicenter} {Epithelial} {Ovarian} {Cancer} {Series}},\n\turl = {https://www.mdpi.com/2075-4426/12/11/1842},\n\tdoi = {10.3390/jpm12111842},\n\tabstract = {Germline and tumor BRCA testing constitutes a valuable tool for clinical decision-making in the management of epithelial ovarian cancer (EOC) patients. Tissue testing is able to identify both germline (g) and somatic (s) BRCA variants, but tissue preservation methods and the widespread implementation of NGS represent pre-analytical and analytical challenges that need to be managed. This study was carried out on a multicenter prospective GEICO cohort of EOC patients with known gBRCA status in order to determine the inter-laboratory reproducibility of tissue sBRCA testing. The study consisted of two independent experimental approaches, a bilateral comparison between two reference laboratories (RLs) testing 82 formalin-paraffin-embedded (FFPE) EOC samples each, and a Ring Test Trial (RTT) with five participating clinical laboratories (CLs) evaluating the performance of tissue BRCA testing in a total of nine samples. Importantly, labs employed their own locally adopted next-generation sequencing (NGS) analytical approach. BRCA mutation frequency in the RL sub-study cohort was 23.17\\%: 12 (63.1\\%) germline and 6 (31.6\\%) somatic. Concordance between the two RLs with respect to BRCA status was 84.2\\% (gBRCA 100\\%). The RTT study distributed a total of nine samples (three commercial synthetic human FFPE references, three FFPE, and three OC DNA) among five CLs. The median concordance detection rate among them was 64.7\\% (range: 35.3–70.6\\%). Analytical discrepancies were mainly due to the minimum variant allele frequency thresholds, bioinformatic pipeline filters, and downstream variant interpretation, some of them with consequences of clinical relevance. Our study demonstrates a wide range of concordance in the identification and interpretation of BRCA sequencing data, highlighting the relevance of establishing standard criteria for detecting, interpreting, and reporting BRCA variants.},\n\tlanguage = {en},\n\tnumber = {11},\n\turldate = {2022-12-13},\n\tjournal = {Journal of Personalized Medicine},\n\tauthor = {Garcia-Casado, Zaida and Oaknin, Ana and Mendiola, Marta and Alkorta-Aranburu, Gorka and Antunez-Lopez, Jose Ramon and Moreno-Bueno, Gema and Palacios, Jose and Yubero, Alfonso and Marquez, Raul and Gallego, Alejandro and Sanchez-Heras, Ana Beatriz and Lopez-Guerrero, Jose Antonio and Perez-Segura, Cristina and Barretina-Ginesta, Pilar and Alarcon, Jesus and Gaba, Lydia and Marquez, Antonia and Matito, Judit and Cueva, Juan and Palacio, Isabel and Iglesias, Maria and Arcusa, Angels and Sanchez-Lorenzo, Luisa and Guerra-Alia, Eva and Romero, Ignacio and Vivancos, Ana},\n\tmonth = nov,\n\tyear = {2022},\n\tnote = {Number: 11\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {BRCA-related cancer, BRCA1/2, DDM v3, miniHRS},\n\tpages = {1842},\n}\n\n

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\n \n\n \n \n \n \n \n \n Testing for homologous recombination repair or homologous recombination deficiency for poly (ADP-ribose) polymerase inhibitors: a current perspective.\n \n \n \n \n\n\n \n Herzog, T. J.; Vergote, I.; Gomella, L. G.; Milenkova, T.; French, T.; Tonikian, R.; Poehlein, C.; and Hussain, M.\n\n\n \n\n\n\n European Journal of Cancer. November 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Testing$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{herzog_testing_2022,\n\ttitle = {Testing for homologous recombination repair or homologous recombination deficiency for poly ({ADP}-ribose) polymerase inhibitors: a current perspective},\n\tissn = {0959-8049},\n\tshorttitle = {Testing for homologous recombination repair or homologous recombination deficiency for poly ({ADP}-ribose) polymerase inhibitors},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0959804922013247},\n\tdoi = {10.1016/j.ejca.2022.10.021},\n\tabstract = {Poly (ADP-ribose) polymerase inhibitors (PARPis) have demonstrated clinical activity in patients with BRCA1 and/or BRCA2 mutated breast, ovarian, prostate, and pancreatic cancers. Notably, BRCA mutations are associated with defects in the homologous recombination repair (HRR) pathway. This homologous recombination deficiency (HRD) phenotype can also be observed as genomic instability in tumor cells. Accordingly, PARPi sensitivity has been observed in various tumors with HRD, independent of BRCA mutations. Currently, four PARPis are approved by regulatory agencies for the treatment of cancer across multiple tumor types. Most indications are specific to tumors with a confirmed BRCA mutation, mutations in other HRR-related genes, HRD evidenced by genomic instability, or evidence of platinum sensitivity. Regulatory agencies have also approved companion and complementary diagnostics to facilitate patient selection for each PARPi indication. This review aims to summarize the biological basis, clinical validation, and clinical relevance of the available diagnostic methods and assays to assess HRD.},\n\tlanguage = {en},\n\turldate = {2022-12-13},\n\tjournal = {European Journal of Cancer},\n\tauthor = {Herzog, Thomas J. and Vergote, Ignace and Gomella, Leonard G. and Milenkova, Tsveta and French, Tim and Tonikian, Raffi and Poehlein, Christian and Hussain, Maha},\n\tmonth = nov,\n\tyear = {2022},\n\tkeywords = {CE-IVD, HRD, HRR, PARPi},\n}\n\n

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\n \n\n \n \n \n \n \n ERBB2 exon 20 insertions are rare in Brazilian non-small cell lung cancer.\n \n \n \n\n\n \n Cavagna, R.; Beatriz; Zaniolo, G.; Fl; Paula, E.; Berardinelli, G.; Santana, I. V.; Caetano, E.; Silva, A.; Josiane; Dias, M.; Alexandre; Jacinto, A.; Rachid; Oliveira, E.; Marchi, P.; Letícia; Leal, F.; Rui; and Reis, R.\n\n\n \n\n\n\n Thoracic cancer, 13. October 2022.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{cavagna_erbb2_2022,\n\ttitle = {{ERBB2} exon 20 insertions are rare in {Brazilian} non-small cell lung cancer},\n\tvolume = {13},\n\tdoi = {10.1111/1759-7714.14605},\n\tabstract = {ERBB2 exon 20 insertions may impact the clinical management of lung cancer patients. However, the frequency of ERBB2 exon 20 insertions in lung cancer patients in Brazil is scarce. Here, we analyzed 722 Brazilian non-small cell lung cancer (NSCLC) patients from Barretos Cancer Hospital that were indicated to require routine lung cancer molecular testing. ERBB2 exon 20 insertions were evaluated by a targeted panel using next-generation sequencing (NGS). Clinicopathological and molecular data were collected from patient medical records. Among the 722 NSCLC patients, 85.2\\% had lung adenocarcinomas, 53.9\\% were male, 66.8\\% were quitter or current smokers, and 63.2\\% were diagnosed at an advanced stage of the disease. We identified 0.8\\% (6/722) of patients who harbored the insertion p.(Tyr772\\_Ala775dup) at exon 20 of the ERBB2 gene. All ERBB2 mutated patients were diagnosed with lung adenocarcinoma, were never smokers, and wild-type for EGFR, KRAS, and ALK hotspot alterations. Less than 1\\% of Brazilian NSCLC patients harbor ERBB2 exon 20 insertions, yet they could benefit in future from the new drugs in development.},\n\tjournal = {Thoracic cancer},\n\tauthor = {Cavagna, Rodrigo and {Beatriz} and Zaniolo, Garbe and {Fl} and Paula, Escremim and Berardinelli, Gustavo and Santana, Iara Viana and Caetano, Eduardo and Silva, Albino and {Josiane} and Dias, Mourão and {Alexandre} and Jacinto, Arthur and {Rachid} and Oliveira, Eduardo and Marchi, Pedro and {Letícia} and Leal, Ferro and {Rui} and Reis, Rui},\n\tmonth = oct,\n\tyear = {2022},\n\tkeywords = {DDM v4.2},\n}\n\n

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\n \n\n \n \n \n \n \n \n High-yield identification of pathogenic NF1 variants by skin fibroblast transcriptome screening after apparently normal diagnostic DNA testing.\n \n \n \n \n\n\n \n Douben, H. C. W.; Nellist, M.; van Unen, L.; Elfferich, P.; Kasteleijn, E.; Hoogeveen-Westerveld, M.; Louwen, J.; van Veghel-Plandsoen, M.; de Valk, W.; Saris, J. J.; Hendriks, F.; Korpershoek, E.; Hoefsloot, L. H.; van Vliet, M.; van Bever, Y.; van de Laar, I.; Aten, E.; Lachmeijer, A. M. A.; Taal, W.; van den Bersselaar, L.; Schuurmans, J.; Oostenbrink, R.; van Minkelen, R.; van Ierland, Y.; and van Ham, T. J.\n\n\n \n\n\n\n Human Mutation, 43(12): 2130–2140. October 2022.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/humu.24487\n\n\n\n
\n\n\n\n \n \n $\"High-yield$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{douben_high-yield_2022,\n\ttitle = {High-yield identification of pathogenic {NF1} variants by skin fibroblast transcriptome screening after apparently normal diagnostic {DNA} testing},\n\tvolume = {43},\n\tissn = {1098-1004},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/humu.24487},\n\tdoi = {10.1002/humu.24487},\n\tabstract = {Neurofibromatosis type 1 (NF1) is caused by inactivating mutations in NF1. Due to the size, complexity, and high mutation rate at the NF1 locus, the identification of causative variants can be challenging. To obtain a molecular diagnosis in 15 individuals meeting diagnostic criteria for NF1, we performed transcriptome analysis (RNA-seq) on RNA obtained from cultured skin fibroblasts. In each case, routine molecular DNA diagnostics had failed to identify a disease-causing variant in NF1. A pathogenic variant or abnormal mRNA splicing was identified in 13 cases: 6 deep intronic variants and 2 transposon insertions causing noncanonical splicing, 3 postzygotic changes, 1 branch point mutation and, in 1 case, abnormal splicing for which the responsible DNA change remains to be identified. These findings helped resolve the molecular findings for an additional 17 individuals in multiple families with NF1, demonstrating the utility of skin-fibroblast-based transcriptome analysis for molecular diagnostics. RNA-seq improves mutation detection in NF1 and provides a powerful complementary approach to DNA-based methods. Importantly, our approach is applicable to other genetic disorders, particularly those caused by a wide variety of variants in a limited number of genes and specifically for individuals in whom routine molecular DNA diagnostics did not identify the causative variant.},\n\tlanguage = {en},\n\tnumber = {12},\n\turldate = {2022-12-13},\n\tjournal = {Human Mutation},\n\tauthor = {Douben, Hannie C. W. and Nellist, Mark and van Unen, Leontine and Elfferich, Peter and Kasteleijn, Esmee and Hoogeveen-Westerveld, Marianne and Louwen, Jesse and van Veghel-Plandsoen, Monique and de Valk, Walter and Saris, Jasper J. and Hendriks, Femke and Korpershoek, Esther and Hoefsloot, Lies H. and van Vliet, Margreethe and van Bever, Yolande and van de Laar, Ingrid and Aten, Emmelien and Lachmeijer, Augusta M. A. and Taal, Walter and van den Bersselaar, Lisa and Schuurmans, Juliette and Oostenbrink, Rianne and van Minkelen, Rick and van Ierland, Yvette and van Ham, Tjakko J.},\n\tmonth = oct,\n\tyear = {2022},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/humu.24487},\n\tkeywords = {AMCG, Alamut Visual v2.15, NF1, RNA},\n\tpages = {2130--2140},\n}\n\n

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\n \n\n \n \n \n \n \n \n Indocyanine green fluorescence patterns of hepatocellular carcinoma correlate with pathological and molecular features.\n \n \n \n \n\n\n \n Sebagh, M.; Desterke, C.; Feray, C.; Hamelin, J.; Habib, M.; Samuel, D.; Rosmorduc, O.; Vibert, E.; and Golse, N.\n\n\n \n\n\n\n HPB. October 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Indocyanine$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{sebagh_indocyanine_2022,\n\ttitle = {Indocyanine green fluorescence patterns of hepatocellular carcinoma correlate with pathological and molecular features},\n\tissn = {1365-182X},\n\turl = {https://www.sciencedirect.com/science/article/pii/S1365182X22016318},\n\tdoi = {10.1016/j.hpb.2022.10.008},\n\tabstract = {Background\nIntraoperative Indocyanine Green Dye (ICG) routinely used in hepatobiliary surgery identifies different fluorescent patterns of hepatocellular carcinoma (HCC), a highly heterogeneous cancer. We aimed to correlate these patterns with gene mutations and extensive pathological features beyond the well-known tumor differentiation.\nMethods\nBetween February 2017 and December 2019, 21 HCC in 16 consecutive patients who underwent intraoperative ICG fluorescence imaging were included. Pathological review was performed by one pathologist blinded to fluorescence features. Random forest machine learning algorithm correlated pathological features of the tumor, peritumoral and non-tumoral liver, and gene mutations from a 28 gene-panel with rim and intra-lesion fluorescence.\nResults\nThree HCC had negative intra-lesion and rim-like emission, 7 HCC had homogeneous pattern and 11 heterogeneous patterns in whom 3 with rim-like emission. Rim emission was associated with peritumoral vascular changes, lower differentiation and lower serum AFP level. Homogeneous intra-lesion fluorescence was associated with lower necrosis rate, thinner capsule, absence of peritumoral liver changes, and higher serum AFP level. Heterogeneous HCC without rim harbored lesser TP53 and ARID1A mutations.\nConclusion\nTumoral and peri-tumoral fluorescence classification of HCC yielded a possible intraoperative pathological and molecular characterization. These preliminary observations could lead to intraoperative refinement in surgical strategy.},\n\tlanguage = {en},\n\turldate = {2022-12-13},\n\tjournal = {HPB},\n\tauthor = {Sebagh, Mylène and Desterke, Christophe and Feray, Cyrille and Hamelin, Jocelyne and Habib, Myriam and Samuel, Didier and Rosmorduc, Olivier and Vibert, Eric and Golse, Nicolas},\n\tmonth = oct,\n\tyear = {2022},\n\tkeywords = {ACAN, CES, DDM},\n}\n\n

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\n \n\n \n \n \n \n \n \n Maturity-onset diabetes of the young in a large Portuguese cohort.\n \n \n \n \n\n\n \n Santos Monteiro, S.; da Silva Santos, T.; Fonseca, L.; Assunção, G.; Lopes, A. M.; Duarte, D. B.; Soares, A. R.; Laranjeira, F.; Ribeiro, I.; Pinto, E.; Rocha, S.; Barbosa Gouveia, S.; Vazquez-Mosquera, M. E.; Oliveira, M. J.; Borges, T.; and Cardoso, M. H.\n\n\n \n\n\n\n Acta Diabetologica. October 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Maturity-onset$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{santos_monteiro_maturity-onset_2022,\n\ttitle = {Maturity-onset diabetes of the young in a large {Portuguese} cohort},\n\tissn = {1432-5233},\n\turl = {https://doi.org/10.1007/s00592-022-01980-2},\n\tdoi = {10.1007/s00592-022-01980-2},\n\tabstract = {Monogenic forms of diabetes that develop with autosomal dominant inheritance are classically aggregated in the Maturity-Onset Diabetes of the Young (MODY) categories. Despite increasing awareness, its true prevalence remains largely underestimated. We describe a Portuguese cohort of individuals with suspected monogenic diabetes who were genetically evaluated for MODY-causing genes.},\n\tlanguage = {en},\n\turldate = {2022-12-13},\n\tjournal = {Acta Diabetologica},\n\tauthor = {Santos Monteiro, Sílvia and da Silva Santos, Tiago and Fonseca, Liliana and Assunção, Guilherme and Lopes, Ana M. and Duarte, Diana B. and Soares, Ana Rita and Laranjeira, Francisco and Ribeiro, Isaura and Pinto, Eugénia and Rocha, Sónia and Barbosa Gouveia, Sofia and Vazquez-Mosquera, María Eugenia and Oliveira, Maria João and Borges, Teresa and Cardoso, Maria Helena},\n\tmonth = oct,\n\tyear = {2022},\n\tkeywords = {CES, MODY, NGS},\n}\n\n

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\n \n\n \n \n \n \n \n \n Delineation of a KDM2B-related neurodevelopmental disorder and its associated DNA methylation signature.\n \n \n \n \n\n\n \n van Jaarsveld, R. H.; Reilly, J.; Cornips, M.; Hadders, M. A.; Agolini, E.; Ahimaz, P.; Anyane-Yeboa, K.; Bellanger, S. A.; van Binsbergen, E.; van den Boogaard, M.; Brischoux-Boucher, E.; Caylor, R. C.; Ciolfi, A.; van Essen, T. A. J.; Fontana, P.; Hopman, S.; Iascone, M.; Javier, M. M.; Kamsteeg, E.; Kerkhof, J.; Kido, J.; Kim, H.; Kleefstra, T.; Lonardo, F.; Lai, A.; Lev, D.; Levy, M. A.; Lewis, M. E. S.; Lichty, A.; Mannens, M. M. A. M.; Matsumoto, N.; Maya, I.; McConkey, H.; Megarbane, A.; Michaud, V.; Miele, E.; Niceta, M.; Novelli, A.; Onesimo, R.; Pfundt, R.; Popp, B.; Prijoles, E.; Relator, R.; Redon, S.; Rots, D.; Rouault, K.; Saida, K.; Schieving, J.; Tartaglia, M.; Tenconi, R.; Uguen, K.; Verbeek, N.; Walsh, C. A.; Yosovich, K.; Yuskaitis, C. J.; Zampino, G.; Sadikovic, B.; Alders, M.; and Oegema, R.\n\n\n \n\n\n\n Genetics in Medicine. September 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Delineation$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{van_jaarsveld_delineation_2022,\n\ttitle = {Delineation of a {KDM2B}-related neurodevelopmental disorder and its associated {DNA} methylation signature},\n\tissn = {1098-3600},\n\turl = {https://www.sciencedirect.com/science/article/pii/S109836002200942X},\n\tdoi = {10.1016/j.gim.2022.09.006},\n\tabstract = {Purpose\nPathogenic variants in genes involved in the epigenetic machinery are an emerging cause of neurodevelopment disorders (NDDs). Lysine-demethylase 2B (KDM2B) encodes an epigenetic regulator and mouse models suggest an important role during development. We set out to determine whether KDM2B variants are associated with NDD.\nMethods\nThrough international collaborations, we collected data on individuals with heterozygous KDM2B variants. We applied methylation arrays on peripheral blood DNA samples to determine a KDM2B associated epigenetic signature.\nResults\nWe recruited a total of 27 individuals with heterozygous variants in KDM2B. We present evidence, including a shared epigenetic signature, to support a pathogenic classification of 15 KDM2B variants and identify the CxxC domain as a mutational hotspot. Both loss-of-function and CxxC-domain missense variants present with a specific subepisignature. Moreover, the KDM2B episignature was identified in the context of a dual molecular diagnosis in multiple individuals. Our efforts resulted in a cohort of 21 individuals with heterozygous (likely) pathogenic variants. Individuals in this cohort present with developmental delay and/or intellectual disability; autism; attention deficit disorder/attention deficit hyperactivity disorder; congenital organ anomalies mainly of the heart, eyes, and urogenital system; and subtle facial dysmorphism.\nConclusion\nPathogenic heterozygous variants in KDM2B are associated with NDD and a specific epigenetic signature detectable in peripheral blood.},\n\tlanguage = {en},\n\turldate = {2022-12-13},\n\tjournal = {Genetics in Medicine},\n\tauthor = {van Jaarsveld, Richard H. and Reilly, Jack and Cornips, Marie-Claire and Hadders, Michael A. and Agolini, Emanuele and Ahimaz, Priyanka and Anyane-Yeboa, Kwame and Bellanger, Severine Audebert and van Binsbergen, Ellen and van den Boogaard, Marie-Jose and Brischoux-Boucher, Elise and Caylor, Raymond C. and Ciolfi, Andrea and van Essen, Ton A. J. and Fontana, Paolo and Hopman, Saskia and Iascone, Maria and Javier, Margaret M. and Kamsteeg, Erik-Jan and Kerkhof, Jennifer and Kido, Jun and Kim, Hyung-Goo and Kleefstra, Tjitske and Lonardo, Fortunato and Lai, Abbe and Lev, Dorit and Levy, Michael A. and Lewis, M. E. Suzanne and Lichty, Angie and Mannens, Marcel M. A. M. and Matsumoto, Naomichi and Maya, Idit and McConkey, Haley and Megarbane, Andre and Michaud, Vincent and Miele, Evelina and Niceta, Marcello and Novelli, Antonio and Onesimo, Roberta and Pfundt, Rolph and Popp, Bernt and Prijoles, Eloise and Relator, Raissa and Redon, Sylvia and Rots, Dmitrijs and Rouault, Karen and Saida, Ken and Schieving, Jolanda and Tartaglia, Marco and Tenconi, Romano and Uguen, Kevin and Verbeek, Nienke and Walsh, Christopher A. and Yosovich, Keren and Yuskaitis, Christopher J. and Zampino, Giuseppe and Sadikovic, Bekim and Alders, Mariëlle and Oegema, Renske},\n\tmonth = sep,\n\tyear = {2022},\n\tkeywords = {Alamut Visual v2.15, KDM2B, MDEMs},\n}\n\n

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\n \n\n \n \n \n \n \n \n Wide range of phenotypic severity in individuals with late truncations unique to the predominant CDKL5 transcript in the brain.\n \n \n \n \n\n\n \n Keehan, L.; Haviland, I.; Gofin, Y.; Swanson, L. C.; El Achkar, C. M.; Schreiber, J.; VanNoy, G. E.; O'Heir, E.; O'Donnell-Luria, A.; Lewis, R. A.; Magoulas, P.; Tran, A.; Azamian, M. S.; Chao, H.; Pham, L.; Samaco, R. C.; Elsea, S.; Thorpe, E.; Kesari, A.; Perry, D.; Lee, B.; Lalani, S. R.; Rosenfeld, J. A.; Olson, H. E.; Burrage, L. C.; and Network, U. D.\n\n\n \n\n\n\n American Journal of Medical Genetics Part A, 188(12): 3516–3524. June 2022.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajmg.a.62940\n\n\n\n
\n\n\n\n \n \n $\"Wide$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{keehan_wide_2022,\n\ttitle = {Wide range of phenotypic severity in individuals with late truncations unique to the predominant {CDKL5} transcript in the brain},\n\tvolume = {188},\n\tissn = {1552-4833},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.62940},\n\tdoi = {10.1002/ajmg.a.62940},\n\tabstract = {Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is caused by heterozygous or hemizygous variants in CDKL5 and is characterized by refractory epilepsy, cognitive and motor impairments, and cerebral visual impairment. CDKL5 has multiple transcripts, of which the longest transcripts, NM\\_003159 and NM\\_001037343, have been used historically in clinical laboratory testing. However, the transcript NM\\_001323289 is the most highly expressed in brain and contains 170 nucleotides at the 3′ end of its last exon that are noncoding in other transcripts. Two truncating variants in this region have been reported in association with a CDD phenotype. To clarify the significance and range of phenotypes associated with late truncating variants in this region of the predominant transcript in the brain, we report detailed information on two individuals, updated clinical information on a third individual, and a summary of published and unpublished individuals reported in ClinVar. The two new individuals (one male and one female) each had a relatively mild clinical presentation including periods of pharmaco-responsive epilepsy, independent walking and limited purposeful communication skills. A previously reported male continued to have a severe phenotype. Overall, variants in this region demonstrate a range of clinical severity consistent with reports in CDD but with the potential for milder presentation.},\n\tlanguage = {en},\n\tnumber = {12},\n\turldate = {2022-11-16},\n\tjournal = {American Journal of Medical Genetics Part A},\n\tauthor = {Keehan, Laura and Haviland, Isabel and Gofin, Yoel and Swanson, Lindsay C. and El Achkar, Christelle Moufawad and Schreiber, John and VanNoy, Grace E. and O'Heir, Emily and O'Donnell-Luria, Anne and Lewis, Richard Alan and Magoulas, Pilar and Tran, Alyssa and Azamian, Mahshid S. and Chao, Hsiao-Tuan and Pham, Lisa and Samaco, Rodney C. and Elsea, Sarah and Thorpe, Erin and Kesari, Akanchha and Perry, Denise and Lee, Brendan and Lalani, Seema R. and Rosenfeld, Jill A. and Olson, Heather E. and Burrage, Lindsay C. and Network, Undiagnosed Diseases},\n\tmonth = jun,\n\tyear = {2022},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajmg.a.62940},\n\tkeywords = {Alamut, Alamut Visual Plus v1.4, CDD, CDKL5},\n\tpages = {3516--3524},\n}\n\n

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\n \n\n \n \n \n \n \n \n Comprehensive Validation of Diagnostic Next-Generation Sequencing Panels for Acute Myeloid Leukemia Patients.\n \n \n \n \n\n\n \n Wagner, U.; Wong, C.; Camenisch, U.; Zimmermann, K.; Rechsteiner, M.; Valtcheva, N.; Theocharides, A.; Widmer, C. C.; Manz, M. G.; Moch, H.; Wild, P. J.; and Balabanov, S.\n\n\n \n\n\n\n The Journal of Molecular Diagnostics, 24(8): 935–954. May 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Comprehensive$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{wagner_comprehensive_2022,\n\ttitle = {Comprehensive {Validation} of {Diagnostic} {Next}-{Generation} {Sequencing} {Panels} for {Acute} {Myeloid} {Leukemia} {Patients}},\n\tvolume = {24},\n\tissn = {1525-1578},\n\turl = {https://www.sciencedirect.com/science/article/pii/S1525157822001593},\n\tdoi = {10.1016/j.jmoldx.2022.05.003},\n\tabstract = {Next-generation sequencing has greatly advanced the molecular diagnostics of malignant hematological diseases and provides useful information for clinical decision making. Studies have shown that certain mutations are associated with prognosis and have a direct impact on treatment of affected patients. Therefore, reliable detection of pathogenic variants is critically important. Here, we compared four sequencing panels with different characteristics, from number of genes covered to technical aspects of library preparation and data analysis workflows, to find the panel with the best clinical utility for myeloid neoplasms with a special focus on acute myeloid leukemia. Using the Acrometrix Oncology Hotspot Control DNA and DNA from acute myeloid leukemia patients, panel performance was evaluated in terms of coverage, precision, recall, and reproducibility and different bioinformatics tools that can be used for the evaluation of any next-generation sequencing panel were tested. Taken together, our results support the reliability of the Acrometrix Oncology Hotspot Control to validate and compare sequencing panels for hematological diseases and show which panel-software combination (platform) has the best performance.},\n\tlanguage = {en},\n\tnumber = {8},\n\turldate = {2022-11-16},\n\tjournal = {The Journal of Molecular Diagnostics},\n\tauthor = {Wagner, Ulrich and Wong, Christine and Camenisch, Ulrike and Zimmermann, Kathrin and Rechsteiner, Markus and Valtcheva, Nadejda and Theocharides, Alexandre and Widmer, Corinne C. and Manz, Markus G. and Moch, Holger and Wild, Peter J. and Balabanov, Stefan},\n\tmonth = may,\n\tyear = {2022},\n\tkeywords = {AML, DDM, MYS},\n\tpages = {935--954},\n}\n\n

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\n \n\n \n \n \n \n \n \n Validation of a new NGS-based myeloid panel in acute myeloid leukemia: A single-center experience.\n \n \n \n \n\n\n \n Steidl, C.; Aroldi, A.; Mologni, L.; Crespiatico, I.; Fontana, D.; Mastini, C.; Fumagalli, M.; Perfetti, P.; Borin, L.; Valentini, C.; Piazza, R.; and Gambacorti-Passerini, C.\n\n\n \n\n\n\n Leukemia Research, 118: 106861. May 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Validation$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{steidl_validation_2022,\n\ttitle = {Validation of a new {NGS}-based myeloid panel in acute myeloid leukemia: {A} single-center experience},\n\tvolume = {118},\n\tissn = {0145-2126},\n\tshorttitle = {Validation of a new {NGS}-based myeloid panel in acute myeloid leukemia},\n\turl = {https://www.sciencedirect.com/science/article/pii/S014521262200087X},\n\tdoi = {10.1016/j.leukres.2022.106861},\n\tabstract = {Acute myeloid leukemia (AML) identifies a heterogeneous group of clonal disorders, both clinically and genetically. A large number of mutations have been described in AML, although only a few are currently employed in clinical practice. Next generation sequencing (NGS) allows for better understanding of the complex genetic background in AML and may direct individualized therapies. In this study, we aim to identify molecular aberrations that are not routinely investigated in AML using an NGS-based panel encompassing 101 genes and to evaluate how their oncogenic potential correlates with survival. Forty consecutive patients with newly diagnosed AML were enrolled between January 2018 and April 2020. We performed targeted NGS and detected 96 mutations in 36 patients (90\\%), while 14 fusion genes were detected in 13 patients (32\\%). Each mutation was weighed using OncoScore, a text-mining tool ranking genes according to their oncogenic potential. An OncoScore ≥ 100 was associated with shorter PFS among our patients (p = 0.05). In 11 patients with no available MRD markers at diagnosis, we were able to perform NGS-based MRD monitoring using targeted deep sequencing. Overall, our study shows that NGS is a powerful tool in AML and should be employed both in routine diagnostic workup and follow up.},\n\tlanguage = {en},\n\turldate = {2022-11-16},\n\tjournal = {Leukemia Research},\n\tauthor = {Steidl, Carolina and Aroldi, Andrea and Mologni, Luca and Crespiatico, Ilaria and Fontana, Diletta and Mastini, Cristina and Fumagalli, Monica and Perfetti, Paola and Borin, Lorenza and Valentini, Claudia and Piazza, Rocco and Gambacorti-Passerini, Carlo},\n\tmonth = may,\n\tyear = {2022},\n\tkeywords = {AML, MYS, NGS},\n\tpages = {106861},\n}\n\n

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\n \n\n \n \n \n \n \n \n RNA-Based Targeted Gene Sequencing Improves the Diagnostic Yield of Mutant Detection in Chronic Myeloid Leukemia.\n \n \n \n \n\n\n \n Shanmuganathan, N.; Wadham, C.; Thomson, D.; Shahrin, N. H.; Vignaud, C.; Obourn, V.; Chaturvedi, S.; Yang, F.; Feng, J.; Saunders, V.; Kok, C. H.; Yeung, D.; King, R. M.; Kenyon, R. R.; Lin, M.; Wang, P.; Scott, H.; Hughes, T.; Schreiber, A. W.; and Branford, S.\n\n\n \n\n\n\n The Journal of Molecular Diagnostics, 24(7): 803–822. April 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"RNA-Based$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{shanmuganathan_rna-based_2022,\n\ttitle = {{RNA}-{Based} {Targeted} {Gene} {Sequencing} {Improves} the {Diagnostic} {Yield} of {Mutant} {Detection} in {Chronic} {Myeloid} {Leukemia}},\n\tvolume = {24},\n\tissn = {1525-1578},\n\turl = {https://www.sciencedirect.com/science/article/pii/S1525157822001167},\n\tdoi = {10.1016/j.jmoldx.2022.04.004},\n\tabstract = {Mutation detection is increasingly used for the management of hematological malignancies. Prior whole transcriptome and whole exome sequencing studies using total RNA and DNA identified diverse mutation types in cancer-related genes associated with treatment failure in patients with chronic myeloid leukemia. Variants included single-nucleotide variants and small insertions/deletions, plus fusion transcripts and partial or whole gene deletions. The hypothesis that all of these mutation types could be detected by a single cost-effective hybridization capture next-generation sequencing method using total RNA was assessed. A method was developed that targeted 130 genes relevant for myeloid and lymphoid leukemia. Retrospective samples with 121 precharacterized variants were tested using total RNA and/or DNA. Concordance of detection of precharacterized variants using RNA or DNA was 96\\%, whereas the enhanced sensitivity identified additional variants. Comparison between 24 matched DNA and RNA samples demonstrated 95.3\\% of 170 variants detectable using DNA were detected using RNA, including all but one variant predicted to activate nonsense-mediated decay. RNA identified an additional 10 variants, including fusion transcripts. Furthermore, the true effect of splice variants on RNA splicing was only evident using RNA. In conclusion, capture sequencing using total RNA alone is suitable for detecting a range of variants relevant in chronic myeloid leukemia and may be more broadly applied to other hematological malignancies where diverse variant types define risk groups.},\n\tlanguage = {en},\n\tnumber = {7},\n\turldate = {2022-11-16},\n\tjournal = {The Journal of Molecular Diagnostics},\n\tauthor = {Shanmuganathan, Naranie and Wadham, Carol and Thomson, Daniel and Shahrin, Nur Hezrin and Vignaud, Chloe and Obourn, Vanessa and Chaturvedi, Shalini and Yang, Feng and Feng, Jinghua and Saunders, Verity and Kok, Chung H. and Yeung, David and King, Rob M. and Kenyon, Rosalie R. and Lin, Ming and Wang, Paul and Scott, Hamish and Hughes, Timothy and Schreiber, Andreas W. and Branford, Susan},\n\tmonth = apr,\n\tyear = {2022},\n\tkeywords = {Alamut, Alamut Visual Plus, RNA},\n\tpages = {803--822},\n}\n\n

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\n \n\n \n \n \n \n \n \n Monogenic diabetes in adults: A multi-ancestry study reveals strong disparities in diagnosis rates and clinical presentation.\n \n \n \n \n\n\n \n Mifsud, F.; Saint-Martin, C.; Dubois-Laforgue, D.; Bouvet, D.; Timsit, J.; and Bellanné-Chantelot, C.\n\n\n \n\n\n\n Diabetes Research and Clinical Practice, 188: 109908. May 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Monogenic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{mifsud_monogenic_2022,\n\ttitle = {Monogenic diabetes in adults: {A} multi-ancestry study reveals strong disparities in diagnosis rates and clinical presentation},\n\tvolume = {188},\n\tissn = {0168-8227},\n\tshorttitle = {Monogenic diabetes in adults},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0168822722007227},\n\tdoi = {10.1016/j.diabres.2022.109908},\n\tabstract = {Aim\nIdentification of monogenic diabetes (MgD) conveys benefits for patients’ care. Algorithms for selecting the patients to be genetically tested have been established in EuroCaucasians, but not in non-EuroCaucasian individuals. We assessed the diagnosis rate, the phenotype of MgD, and the relevance of selection criteria, according to ancestry in patients referred for a suspected MgD.\nMethods\nSeven genes (GCK, HNF1A, HNF4A, HNF1B, ABCC8, KCNJ11, INS) were analyzed in 1975 adult probands (42\\% non-EuroCaucasians), selected on the absence of diabetes autoantibodies and ≥2 of the following criteria: age ≤40 years and body mass index {\\textless}30 kg/m2 at diagnosis, and a family history of diabetes in ≥2 generations.\nResults\nPathogenic/likely pathogenic variants were identified in 6.2\\% of non-EuroCaucasian and 23.6\\% of EuroCaucasian patients (OR 0.21, [0.16–0.29]). Diagnosis rate was low in all non-EuroCaucasian subgroups (4.1–11.8\\%). Common causes of MgD (GCK, HNF1A, HNF4A), but not rare causes, were less frequent in non-EuroCaucasians than in EuroCaucasians (4.1\\%, vs. 21.1\\%, OR 0.16 [0.11–0.23]). Using ethnicity-specific body mass index cutoffs increased the diagnosis rate in several non-EuroCaucasian subgroups.\nConclusion\nThe diagnosis rate of MgD is low in non-EuroCaucasian patients, but may be improved by tailoring selection criteria according to patients’ancestry.},\n\tlanguage = {en},\n\turldate = {2022-11-16},\n\tjournal = {Diabetes Research and Clinical Practice},\n\tauthor = {Mifsud, F. and Saint-Martin, C. and Dubois-Laforgue, D. and Bouvet, D. and Timsit, J. and Bellanné-Chantelot, C.},\n\tmonth = may,\n\tyear = {2022},\n\tkeywords = {Alamut Visual v2.15},\n\tpages = {109908},\n}\n\n

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\n \n\n \n \n \n \n \n \n Prognostic impact of early minimal residual disease combined with complete molecular evaluation in acute myeloid leukemia with mutated NPM1: a single center study.\n \n \n \n \n\n\n \n Memoli, M.; Genthon, A.; Favale, F.; Lapusan, S.; Johnson, N.; Adaeva, R.; Deswarte, C.; Battipaglia, G.; Malard, F.; Duléry, R.; Brissot, E.; Banet, A.; Van de Wyngaert, Z.; Mohty, M.; Delhommeau, F.; Legrand, O.; and Hirsch, P.\n\n\n \n\n\n\n Leukemia & Lymphoma, 63(9): 2171–2179. April 2022.\n Publisher: Taylor & Francis _eprint: https://doi.org/10.1080/10428194.2022.2064987\n\n\n\n
\n\n\n\n \n \n $\"Prognostic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{memoli_prognostic_2022,\n\ttitle = {Prognostic impact of early minimal residual disease combined with complete molecular evaluation in acute myeloid leukemia with mutated {NPM1}: a single center study},\n\tvolume = {63},\n\tissn = {1042-8194},\n\tshorttitle = {Prognostic impact of early minimal residual disease combined with complete molecular evaluation in acute myeloid leukemia with mutated {NPM1}},\n\turl = {https://doi.org/10.1080/10428194.2022.2064987},\n\tdoi = {10.1080/10428194.2022.2064987},\n\tabstract = {We evaluated prognostic factors in 83 intensively treated adult patients with NPM1 mutated AML. Targeted next-generation sequencing revealed high frequency of co-mutations in epigenetic modifiers or proliferation pathways. NPM1 minimal residual disease (MRD), assessed in bone marrow by specific polymerase chain reaction after one chemotherapy course, was {\\textgreater}0.01\\% in 50 patients considered poor responders (PR). On multivariate analysis, including all variables with a p value {\\textless}.1 on univariate analysis, age {\\textgreater}60, performance status (PS) ≥1, presence of FLT3 mutations, DNMT3A-R882, and PR status, were independently associated with lower leukemia-free survival. Age {\\textgreater}60, a previous hematological disease and PR status were independent negative predictive factors for overall survival. In our study, early NPM1 MRD was confirmed as an important prognostic factor. All FLT3 and DNMT3A-R882 mutations have also an independent prognostic value. We support the rational for in-depth investigations for a better approach in patients who achieving a first complete remission.},\n\tnumber = {9},\n\turldate = {2022-11-16},\n\tjournal = {Leukemia \\& Lymphoma},\n\tauthor = {Memoli, Mara and Genthon, Alexis and Favale, Fabrizia and Lapusan, Simona and Johnson, Natacha and Adaeva, Rosa and Deswarte, Caroline and Battipaglia, Giorgia and Malard, Florent and Duléry, Rémy and Brissot, Eolia and Banet, Anne and Van de Wyngaert, Zoé and Mohty, Mohamad and Delhommeau, François and Legrand, Ollivier and Hirsch, Pierre},\n\tmonth = apr,\n\tyear = {2022},\n\tpmid = {35459427},\n\tnote = {Publisher: Taylor \\& Francis\n\\_eprint: https://doi.org/10.1080/10428194.2022.2064987},\n\tkeywords = {AML, DDM, DDM v5.0.12, NPM1},\n\tpages = {2171--2179},\n}\n\n

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\n \n\n \n \n \n \n \n \n Clinical and molecular genetic analysis of early-onset myopathy with fatal cardiomyopathy: Novel biallelic M-line TTN mutation and review of the literature.\n \n \n \n \n\n\n \n El Kadiri, Y.; Ratbi, I.; Sefiani, A.; and Lyahyai, J.\n\n\n \n\n\n\n Gene Reports, 27: 101587. March 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Clinical$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{el_kadiri_clinical_2022,\n\ttitle = {Clinical and molecular genetic analysis of early-onset myopathy with fatal cardiomyopathy: {Novel} biallelic {M}-line {TTN} mutation and review of the literature},\n\tvolume = {27},\n\tissn = {2452-0144},\n\tshorttitle = {Clinical and molecular genetic analysis of early-onset myopathy with fatal cardiomyopathy},\n\turl = {https://www.sciencedirect.com/science/article/pii/S2452014422000954},\n\tdoi = {10.1016/j.genrep.2022.101587},\n\tabstract = {Early-onset myopathy with fatal cardiomyopathy (EOMFC), also known as Salih myopathy (SALMY) is a rare, heterogeneous, and severe form of titinopathies with autosomal recessive inherited neuromuscular disorders that affects both skeletal and cardiac muscles. It was previously identified only in the Arab population with unknown incidence. Titin (TTN) mutations that have been reported in congenital myopathies are associated with a variety of phenotypic spectrum of titinopathies, which are scattered along with the 364 exons of the gene. In this study, we report a consanguineous Moroccan female child aged 29 months who presented with congenital myopathy associated to dilated cardiomyopathy. Clinical Exome Sequencing identified a novel homozygous truncating mutation c.106541delA p.(Asp35514Valfs*32) in exon 361 of the TTN gene. Sanger sequencing confirmed the mutation in a homozygous state in the proband and in a heterozygous state in both of her parents. Clinical and molecular data of the proband were correlated with 15 patients reported in the literature for congenital myopathy associated to a heart defect or development of dilated cardiomyopathy with at least one mutant allele in the M-band titin protein as inclusion criteria. In conclusion, the application of NGS in rare genetic heterogeneous forms as EOMFC provides more evidently an increasing proportion of congenital myopathies than currently recognized and expands the mutation spectrum of the TTN gene for better guiding the genetic diagnosis with adequate genetic counseling to the Moroccan families.},\n\tlanguage = {en},\n\turldate = {2022-11-16},\n\tjournal = {Gene Reports},\n\tauthor = {El Kadiri, Youssef and Ratbi, Ilham and Sefiani, Abdelaziz and Lyahyai, Jaber},\n\tmonth = mar,\n\tyear = {2022},\n\tkeywords = {CES v2, DDM, DDM v.5.7.7, DDM v5.7.7, M-line titin exons, TTN},\n\tpages = {101587},\n}\n\n

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\n \n\n \n \n \n \n \n \n Pralsetinib and Sequential MET Inhibitors to Overcome MET Amplification Resistance in a Patient With a RET Fusion Driven Lung Cancer - Case Report.\n \n \n \n \n\n\n \n P, W.; L, M.; F, K.; K, K.; A, D.; R, L.; J, C.; and V, F.\n\n\n \n\n\n\n Clinical lung cancer. August 2022.\n Publisher: Clin Lung Cancer\n\n\n\n
\n\n\n\n \n \n $\"Pralsetinib$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{p_pralsetinib_2022,\n\ttitle = {Pralsetinib and {Sequential} {MET} {Inhibitors} to {Overcome} {MET} {Amplification} {Resistance} in a {Patient} {With} a {RET} {Fusion} {Driven} {Lung} {Cancer} - {Case} {Report}},\n\tissn = {1938-0690},\n\turl = {https://pubmed.ncbi.nlm.nih.gov/36127251/},\n\tdoi = {10.1016/j.cllc.2022.08.010},\n\tabstract = {Pralsetinib and Sequential MET Inhibitors to Overcome MET Amplification Resistance in a Patient With a RET Fusion Driven Lung Cancer - Case Report},\n\tlanguage = {en},\n\turldate = {2022-11-15},\n\tjournal = {Clinical lung cancer},\n\tauthor = {P, Wang and L, Matton and F, Kebir and K, Kerrou and A, Dubois and R, Lacave and J, Cadranel and V, Fallet},\n\tmonth = aug,\n\tyear = {2022},\n\tpmid = {36127251},\n\tnote = {Publisher: Clin Lung Cancer},\n\tkeywords = {MET, NGS},\n}\n\n

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\n \n\n \n \n \n \n \n \n Identification of Alpha Thalassemia, RNF213 p.R4810K and PROC p.R189W among Children with Moyamoya Disease/Syndrome.\n \n \n \n \n\n\n \n Thampratankul, L.; Okuno, Y.; Komvilaisak, P.; Wattanasirichaigoon, D.; and Sirachainan, N.\n\n\n \n\n\n\n Mediterranean Journal of Hematology and Infectious Diseases, 14(1): e2022057. July 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Identification$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{thampratankul_identification_2022,\n\ttitle = {Identification of {Alpha} {Thalassemia}, {RNF213} p.{R4810K} and {PROC} p.{R189W} among {Children} with {Moyamoya} {Disease}/{Syndrome}},\n\tvolume = {14},\n\tissn = {2035-3006},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266462/},\n\tdoi = {10.4084/MJHID.2022.057},\n\tnumber = {1},\n\turldate = {2022-11-15},\n\tjournal = {Mediterranean Journal of Hematology and Infectious Diseases},\n\tauthor = {Thampratankul, Lunliya and Okuno, Yusuke and Komvilaisak, Patcharee and Wattanasirichaigoon, Duangrurdee and Sirachainan, Nongnuch},\n\tmonth = jul,\n\tyear = {2022},\n\tpmid = {35865395},\n\tpmcid = {PMC9266462},\n\tkeywords = {DDM, DDM v4.4, External KIT, WES pipeline},\n\tpages = {e2022057},\n}\n\n

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\n \n\n \n \n \n \n \n \n Biallelic PMS2 Mutations in a Family with Uncommon Clinical and Molecular Features.\n \n \n \n \n\n\n \n Pedroni, M.; Ponz de Leon, M.; Reggiani Bonetti, L.; Rossi, G.; Viel, A.; Urso, E. D. L.; and Roncucci, L.\n\n\n \n\n\n\n Genes, 13(11): 1953. October 2022.\n Number: 11 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Biallelic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{pedroni_biallelic_2022,\n\ttitle = {Biallelic {PMS2} {Mutations} in a {Family} with {Uncommon} {Clinical} and {Molecular} {Features}},\n\tvolume = {13},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2073-4425},\n\turl = {https://www.mdpi.com/2073-4425/13/11/1953},\n\tdoi = {10.3390/genes13111953},\n\tabstract = {We describe a patient with constitutional mismatch repair-deficiency (CMMR-D) in whom the syndrome started at age 10 with the development of multiple adenomas in the large bowel. In the successive 25 years, four malignancies developed in different organs (rectum, ileum, duodenum, and lymphoid tissue). The patient had biallelic constitutional pathogenic variants in the PMS2 gene. We speculate that besides the PMS2 genotype, alterations of other genes might have contributed to the development of the complex phenotype. In the nuclear family, both parents carried different PMS2 germline mutations. They appeared in good clinical condition and did not develop polyps or cancer. The index case had a brother who died at age three of lymphoblastic leukemia, and a sister who was affected by sarcoidosis. Tumor tissue showed diffuse DNA microsatellite instability. A complete absence of immunoreactivity was observed for the PMS2 protein both in the tumors and normal tissues. Next-generation sequencing and multiple ligation-dependent probe amplification analyses revealed biallelic PMS2 germline pathogenic variants in the proband (genotype c.[137G{\\textgreater}T];[(2174+1\\_2175-1)\\_(*160\\_?)del]), and one of the two variants was present in both parents—c.137G{\\textgreater}T in the father and c.(2174+1-2175-1)\\_(*160\\_?)del in the mother—as well as c.137G{\\textgreater}T in the sister. Moreover, Class 3 variants of MSH2 (c.1787A{\\textgreater}G), APC (c.1589T{\\textgreater}C), and CHEK2 (c.331G{\\textgreater}T) genes were also detected in the proband. In conclusion, the recognition of CMMR-D may sometimes be difficult; however, the possible role of constitutional alterations of other genes in the development of the full-blown phenotype should be investigated in more detail.},\n\tlanguage = {en},\n\tnumber = {11},\n\turldate = {2022-11-15},\n\tjournal = {Genes},\n\tauthor = {Pedroni, Monica and Ponz de Leon, Maurizio and Reggiani Bonetti, Luca and Rossi, Giuseppina and Viel, Alessandra and Urso, Emanuele Damiano Luca and Roncucci, Luca},\n\tmonth = oct,\n\tyear = {2022},\n\tnote = {Number: 11\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {CMMR-D, DDM, HCS, VUS},\n\tpages = {1953},\n}\n\n

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\n \n\n \n \n \n \n \n \n Genomic alterations in a cohort of pediatric acute myeloid leukemia patients at two cancer centers in Colombia.\n \n \n \n \n\n\n \n Yunis, L. K.; Linares-Ballesteros, A.; Barros, G.; Garcia, J.; Aponte, N.; Niño, L.; Uribe, G.; Quintero, E.; Perez, J.; Martinez, L.; and Yunis, J. J.\n\n\n \n\n\n\n International Journal of Hematology. October 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Genomic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{yunis_genomic_2022,\n\ttitle = {Genomic alterations in a cohort of pediatric acute myeloid leukemia patients at two cancer centers in {Colombia}},\n\tissn = {0925-5710, 1865-3774},\n\turl = {https://link.springer.com/10.1007/s12185-022-03475-w},\n\tdoi = {10.1007/s12185-022-03475-w},\n\tabstract = {Few studies identifying genomic aspects in pediatric acute myeloid leukemia patients in Latin American countries have been reported. The aim of this study was to identify genomic alterations, clinical characteristics and outcomes in a cohort of pediatric AML patients. This descriptive observational cohort study included patients with confirmed de novo acute myeloid leukemia up to 18 years of age. Cytogenetics and conventional FISH analysis, next-generation sequencing and PCR testing were performed. The correlation of genomic data with treatment response and outcomes were analyzed. Of the 51 patients analyzed, 67.4\\% had a cytogenetic abnormality and 74.5\\% had a genetic variant. FLT3 variants (ITD or TKD D835) were found in 27.4\\%, followed by NRAS (21.6\\%), KRAS (13.7\\%) and WT1 and KIT (11.8\\%). Patients were stratified by risk (66.6\\% high-risk) after the end of induction. FLT3-ITD was associated with relapse (OR 11.25; CI 1.89–66.72, p 0.006) and NRAS with death during induction (OR 16.71; CI 1.51–184.59, p 0.022). Our study highlights the importance of rapid incorporation of genetic testing in pediatric AML in Colombia, as it directly affects treatment decisions and outcomes. Incorporation of targeted therapies with conventional chemotherapy is an increasingly urgent need in pediatric patients.},\n\tlanguage = {en},\n\turldate = {2022-11-15},\n\tjournal = {International Journal of Hematology},\n\tauthor = {Yunis, Luz K. and Linares-Ballesteros, Adriana and Barros, Gisela and Garcia, Johnny and Aponte, Nelson and Niño, Laura and Uribe, Gloria and Quintero, Edna and Perez, Jaime and Martinez, Leila and Yunis, Juan J.},\n\tmonth = oct,\n\tyear = {2022},\n\tkeywords = {DDM, DDM v5.2.7.1, MYS, MYS plus, MYS+},\n}\n\n

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\n \n\n \n \n \n \n \n 2022-RA-913-ESGO Clinical performance evaluation of a novel deep learning solution for homologous recombination deficiency detection.\n \n \n \n\n\n \n \n\n\n \n\n\n\n ,2. October 2022.\n \n\n\n\n
\n\n\n\n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{noauthor_2022-ra-913-esgo_2022,\n\ttitle = {2022-{RA}-913-{ESGO} {Clinical} performance evaluation of a novel deep learning solution for homologous recombination deficiency detection},\n\tabstract = {Introduction/Background Standard of care chemotherapy in patients (pts) with advanced ovarian cancer (AOC) is the combination of carboplatin and paclitaxel (C/P). Data from the PRIMA trial has shown a significant benefit in pts by the addition of a maintenance treatment (MT) with niraparib irrespective of BRCA or HRD-status in high-grade AOC. The PAOLA-1 trial evaluated MT in pts with AOC with the combination of olaparib and bevacizumab and has also shown a significant benefit compared to bevacizumab monotherapy. However, the role/benefit of bevacizumab in addition to PARP-inhibitor (PARPi) in MT is unclear. Therefore, we investigate, if the treatment strategy of carboplatin/paclitaxel/bevacizumab/PARPi is superior to the treatment of carboplatin/ paclitaxel/PARPi in a population regardless of biomarker status.\nMethodology AGO-OVAR 28/ENGOT-ov57 (NCT05009082; EudraCT-Number: 2021–001271–16) is a multicenter, randomized, prospective phase III trial. The trial population is composed of adult pts with newly diagnosed, high-grade epithelial AOC, primary peritoneal cancer or fallopian tube cancer FIGO III/IV (except FIGO IIIA2 without nodal involvement). All pts should have completed cycle1 of chemotherapy (C/P) as part of Study-Run-In-Period. Prior to day1 of cycle2, pts with a valid central tumor BRCA (tBRCA) test result will be randomized 1:1 into either Arm1 and will receive 5 additional cycles of C/P q21d followed by niraparib for up to 3 years; or into Arm2 where pts will receive 5 additional cycles of C/P plus bevacizumab q21d followed by bevacizumab q21d (for up to 1 year) and niraparib for up to 3 years. Patients who are scheduled for neoadjuvant chemotherapy and interval debulking surgery can also be enrolled. The primary objective is progressionfree-survival (PFS). Secondary objectives include but are not limited to: PFS according to tBRCA-status, overall survival, PFS2, safety/tolerability, and quality of life. First-PatientFirst-Visit is expected in August 2022. Target recruitment is 970 patients.\nResults Trial-In-Progress.\nConclusion Trial-In-Progress.},\n\tlanguage = {en},\n\tmonth = oct,\n\tyear = {2022},\n\tkeywords = {DDM, HRD, Myriad},\n\tpages = {2},\n}\n\n

\n\n\n

\n Introduction/Background Standard of care chemotherapy in patients (pts) with advanced ovarian cancer (AOC) is the combination of carboplatin and paclitaxel (C/P). Data from the PRIMA trial has shown a significant benefit in pts by the addition of a maintenance treatment (MT) with niraparib irrespective of BRCA or HRD-status in high-grade AOC. The PAOLA-1 trial evaluated MT in pts with AOC with the combination of olaparib and bevacizumab and has also shown a significant benefit compared to bevacizumab monotherapy. However, the role/benefit of bevacizumab in addition to PARP-inhibitor (PARPi) in MT is unclear. Therefore, we investigate, if the treatment strategy of carboplatin/paclitaxel/bevacizumab/PARPi is superior to the treatment of carboplatin/ paclitaxel/PARPi in a population regardless of biomarker status. Methodology AGO-OVAR 28/ENGOT-ov57 (NCT05009082; EudraCT-Number: 2021–001271–16) is a multicenter, randomized, prospective phase III trial. The trial population is composed of adult pts with newly diagnosed, high-grade epithelial AOC, primary peritoneal cancer or fallopian tube cancer FIGO III/IV (except FIGO IIIA2 without nodal involvement). All pts should have completed cycle1 of chemotherapy (C/P) as part of Study-Run-In-Period. Prior to day1 of cycle2, pts with a valid central tumor BRCA (tBRCA) test result will be randomized 1:1 into either Arm1 and will receive 5 additional cycles of C/P q21d followed by niraparib for up to 3 years; or into Arm2 where pts will receive 5 additional cycles of C/P plus bevacizumab q21d followed by bevacizumab q21d (for up to 1 year) and niraparib for up to 3 years. Patients who are scheduled for neoadjuvant chemotherapy and interval debulking surgery can also be enrolled. The primary objective is progressionfree-survival (PFS). Secondary objectives include but are not limited to: PFS according to tBRCA-status, overall survival, PFS2, safety/tolerability, and quality of life. First-PatientFirst-Visit is expected in August 2022. Target recruitment is 970 patients. Results Trial-In-Progress. Conclusion Trial-In-Progress.\n

\n\n\n

\n \n\n \n \n \n \n \n \n Novel Cranial Imaging Findings and a Splice-Site Variant in a Patient with Tyrosinemia Type III, and a Summary of Published Cases.\n \n \n \n \n\n\n \n Kahraman, A. B.; Akar, H. T.; Lafcı, N. G.; Yıldız, Y.; and Tokatlı, A.\n\n\n \n\n\n\n Molecular Syndromology, 13(3): 193–199. January 2022.\n Publisher: Karger Publishers\n\n\n\n
\n\n\n\n \n \n $\"Novel$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{kahraman_novel_2022,\n\ttitle = {Novel {Cranial} {Imaging} {Findings} and a {Splice}-{Site} {Variant} in a {Patient} with {Tyrosinemia} {Type} {III}, and a {Summary} of {Published} {Cases}},\n\tvolume = {13},\n\tissn = {1661-8769, 1661-8777},\n\turl = {https://www.karger.com/Article/FullText/519256},\n\tdoi = {10.1159/000519256},\n\tabstract = {Tyrosinemia type III is an extremely rare autosomal recessive disease, with only 19 patients yet reported. It is caused by a deficiency of the 4-hydroxyphenylpyruvate dioxygenase enzyme, resulting from biallelic mutations in the \\textit{HPD} gene. Although the clinical spectrum of the disease is not fully known, most patients present with neurodevelopmental symptoms. We report on a 20-month-old patient who was investigated due to developmental delay and dysmorphic features. The girl had a novel splice-site mutation in the \\textit{HPD} gene and ventriculomegaly in cranial imaging, which was not previously associated with tyrosinemia type III. Our patient had mild subjective improvement in social skills and language development after dietary therapy was started and her tyrosine levels decreased. We also summarize clinical, biochemical, and genetic findings of previously published patients with biallelic \\textit{HPD} mutations.},\n\tlanguage = {english},\n\tnumber = {3},\n\turldate = {2022-11-15},\n\tjournal = {Molecular Syndromology},\n\tauthor = {Kahraman, Ayca Burcu and Akar, Halil Tuna and Lafcı, Naz Güleray and Yıldız, Yılmaz and Tokatlı, Ayşegül},\n\tmonth = jan,\n\tyear = {2022},\n\tpmid = {35707594},\n\tnote = {Publisher: Karger Publishers},\n\tkeywords = {HCS, HPD},\n\tpages = {193--199},\n}\n\n

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\n \n\n \n \n \n \n \n \n BRCA1 and BRCA2 germline mutation analysis from a cohort of 1,267 high-risk breast cancer patients in Brazil.\n \n \n \n \n\n\n \n Villela, D.; Mazzonetto, P.; Milanezi, F.; Andrea, M.; Martins, S.; Monfredini, P. M.; Silva, J. d. S.; Perrone, E.; Schnabel, B.; Nakano, V.; Palmero, E.; Braggio, E.; Cavalcanti, T. L.; Guida, G.; Migliavacca, M. P.; Scapulatempo-Neto, C.; and Zalcberg, I.\n\n\n \n\n\n\n Technical Report In Review, August 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"BRCA1$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@techreport{villela_brca1_2022,\n\ttype = {preprint},\n\ttitle = {{BRCA1} and {BRCA2} germline mutation analysis from a cohort of 1,267 high-risk breast cancer patients in {Brazil}},\n\turl = {https://www.researchsquare.com/article/rs-1942605/v1},\n\tabstract = {Abstract\n          \n            We determined the frequency and mutational spectrum of\n            BRCA1\n            and\n            BRCA2\n            in a series of high-risk breast cancer patients from Brazil. A total of 1,267 patients were referred for\n            BRCA\n            genetic testing, and no obligation of fulfilling criteria of mutation probability methods for molecular screening was applied. Germline deleterious mutations in\n            BRCA1/2\n            (i.e. pathogenic/ likely pathogenic variants) were identified in 156 out of 1267 patients (12\\%). We confirm recurrent mutations in\n            BRCA1/2\n            , but we also report three novel mutations in\n            BRCA2\n            , not previously reported in any public databases or other studies. Variants of unknown significance (VUS) represent only 2\\% in this dataset and most of them were detected in\n            BRCA2\n            . The overall mutation prevalence in\n            BRCA1/2\n            was higher in patients diagnosed with cancer at age {\\textgreater} 35 years old, and with family history of cancer. The present data expand our knowledge of\n            BRCA1/2\n            germline mutational spectrum, and it is a valuable clinical resource for genetic counseling and cancer management programs in the country.},\n\tlanguage = {en},\n\turldate = {2022-10-25},\n\tinstitution = {In Review},\n\tauthor = {Villela, Darine and Mazzonetto, Patricia and Milanezi, Fernanda and Andrea, Mariana and Martins, Sylvia and Monfredini, Priscilla M. and Silva, Juliana dos Santos and Perrone, Eduardo and Schnabel, Beatriz and Nakano, Viviane and Palmero, Edenir and Braggio, Esteban and Cavalcanti, Thereza Loureiro and Guida, Gustavo and Migliavacca, Michele Patricia and Scapulatempo-Neto, Cristovam and Zalcberg, Ilana},\n\tmonth = aug,\n\tyear = {2022},\n\tdoi = {10.21203/rs.3.rs-1942605/v1},\n\tkeywords = {Alamut Visual Plus, BRCA1, BRCA2, DDM, HCS},\n}\n\n

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\n \n\n \n \n \n \n \n \n A novel germline mutation of the PALB gene in a young Yakut breast cancer woman.\n \n \n \n \n\n\n \n Gervas, P. A.; Molokov, A. Y.; Zarubin, A. A.; Ivanova, A. A.; Tikhonov, D. G.; Kipriyanova, N. S.; Egorov, A. N.; Zhuikova, L. D.; Shefer, N. A.; Topolnitskiy, E. B.; Belyavskaya, V. A.; Pisareva, L. F.; Choynzonov, E. L.; and Cherdyntseva, N. V.\n\n\n \n\n\n\n Siberian journal of oncology, 21(4): 72–79. September 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{gervas_novel_2022,\n\ttitle = {A novel germline mutation of the \\textit{{PALB}} gene in a young {Yakut} breast cancer woman},\n\tvolume = {21},\n\tissn = {2312-3168, 1814-4861},\n\turl = {https://www.siboncoj.ru/jour/article/view/2235},\n\tdoi = {10.21294/1814-4861-2022-21-4-72-79},\n\tabstract = {Background. Breast cancer (BC) is the most common female malignancy worldwide. Partner And Localizer of BRCA2 gene (PALB2) is directly involved in DNA damage response. Germline mutation in PALB2 has been identified in breast cancer and familial pancreatic cancer cases, accounting for approximately 1–2\\% and 3–4\\%, respectively. The goal of this report was to describe new PALB2 mutation in a young Yakut breast cancer patient with family history of cancer. Material and Methods. Genomic DNA were isolated from blood samples and used to prepare libraries using a capture-based target enrichment kit, Hereditary Cancer Solution™ (SOPHiA GENETICS, Switzerland), covering 27 genes (ATM, APC, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, FAM175A, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PALB2, PIK3CA, PMS2, PMS2CL, PTEN, RAD50, RAD51C, RAD51D, STK11, TP53 and XRCC2). Paired-end sequencing (2 × 150 bp) was conducted using NextSeq 500 system (Illumina, USA). Results. Here we describe a case of a never-before-reported mutation in the PALB2 gene that led to the early onset breast cancer. We report the case of a 39-year-old breast cancer Yakut woman with a family history of pancreatic cancer. Bioinformatics analysis of the NGS data revealed the presence of the new PALB2 gene germinal frameshift deletion (NM\\_024675:exon1:c.47delA:p.K16fs). In accordance with dbPubMed ClinVar, new mutation is located in codon of the PALB2 gene, where the likely pathogenic donor splice site mutation (NM\\_024675.3:c.48+1delG) associated with hereditary cancer-predisposing syndrome has been earlier described. Conclusion. We found a new never-before-reported mutation in PALB2 gene, which probably associated with early onset breast cancer in Yakut indigenous women with a family history of pancreatic cancer.},\n\tlanguage = {en},\n\tnumber = {4},\n\turldate = {2022-10-25},\n\tjournal = {Siberian journal of oncology},\n\tauthor = {Gervas, P. A. and Molokov, A. Yu. and Zarubin, A. A. and Ivanova, A. A. and Tikhonov, D. G. and Kipriyanova, N. S. and Egorov, A. N. and Zhuikova, L. D. and Shefer, N. A. and Topolnitskiy, E. B. and Belyavskaya, V. A. and Pisareva, L. F. and Choynzonov, E. L. and Cherdyntseva, N. V.},\n\tmonth = sep,\n\tyear = {2022},\n\tkeywords = {BRCA1, HCS, NGS, PALB2},\n\tpages = {72--79},\n}\n\n

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\n \n\n \n \n \n \n \n \n ARTIFICIAL INTELLIGENCE AND BLOCKCHAIN IN HEALTHCARE.\n \n \n \n \n\n\n \n Dziatkovskii, A.\n\n\n \n\n\n\n . September 2022.\n Publisher: Zenodo\n\n\n\n
\n\n\n\n \n \n $\"ARTIFICIAL$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{dziatkovskii_artificial_2022,\n\ttitle = {{ARTIFICIAL} {INTELLIGENCE} {AND} {BLOCKCHAIN} {IN} {HEALTHCARE}},\n\tcopyright = {Creative Commons Attribution 4.0 International, Open Access},\n\turl = {https://zenodo.org/record/7045990},\n\tdoi = {10.5281/ZENODO.7045990},\n\tabstract = {The article is devoted to increasing the efficiency of blockchain technology and artificial intelligence in the field of health care in their combination. The problem of a high number of medical errors and the possibility of informatization of the health sector is put. Examples of advantages and weaknesses of both technologies are given. It is proved that the combination of artificial intelligence and blockchain can improve the security of big data, make decisions made by artificial intelligence more transparent, explainable and trustworthy, to reduce the number of medical errors, to make a step towards individualized medicine.},\n\tlanguage = {en},\n\turldate = {2022-10-25},\n\tauthor = {Dziatkovskii, A.},\n\tmonth = sep,\n\tyear = {2022},\n\tnote = {Publisher: Zenodo},\n\tkeywords = {Artificial intelligence, DDM},\n}\n\n

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\n \n\n \n \n \n \n \n \n In-house testing for homologous recombination repair deficiency (HRD) testing in ovarian carcinoma: a feasibility study comparing AmoyDx HRD Focus panel with Myriad myChoiceCDx assay.\n \n \n \n \n\n\n \n Fumagalli, C.; Betella, I.; Ranghiero, A.; Guerini-Rocco, E.; Bonaldo, G.; Rappa, A.; Vacirca, D.; Colombo, N.; and Barberis, M.\n\n\n \n\n\n\n Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology, 114: 288–294. September 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"In-house$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{fumagalli_-house_2022,\n\ttitle = {In-house testing for homologous recombination repair deficiency ({HRD}) testing in ovarian carcinoma: a feasibility study comparing {AmoyDx} {HRD} {Focus} panel with {Myriad} {myChoiceCDx} assay},\n\tvolume = {114},\n\tcopyright = {Copyright (c) 2022 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology},\n\tissn = {1591-951X},\n\tshorttitle = {In-house testing for homologous recombination repair deficiency ({HRD}) testing in ovarian carcinoma},\n\turl = {https://www.pathologica.it/article/view/791},\n\tdoi = {10.32074/1591-951X-791},\n\tabstract = {Background. Homologous recombination repair (HRR) is the main mechanism of repair of DNA double-strand breaks. Its deficiency (HRD) is a common feature of epithelial ovarian cancers (EOCs). BRCA1/2 mutations and/or other aberrations in genes of HRR are well known causes of HRD and genomic instability. Poly ADP-ribose polymerase inhibitors (PARPi) have revolutionized the management of BRCA mutant EOCs and demonstrated activity in HRD tumor cells. Determining HRD status can provide informations on the magnitude of benefit for PARPi therapy. Myriad MyChoice CDx is a next generation sequencing- based in vitro diagnostic test that assesses the Genomic Instability Score (GIS) which is an algorithmic measurement of loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions using DNA isolated from formalin-fixed paraffin embedded tumor tissue specimens. However Myriad MyChoice CDx, is a centrally performed and costly assay, with no reimbursement scheduled, at least in Italy. Methods. In this report, we described our experience in performing the HRD Focus AmoyDx (Amoy Diagnostics Ltd, Xiamen, Fujian, China) on the same samples of EOCs evaluated with Myriad MyChoiceCDx assay. Results. The overall percent agreement between AmoyDx and Myriad was 87.8\\% (65 of 74 tumors tested). All the 36 AmoyDx negative cases were confirmed to be negative by Myriad (negative predictive value, 100\\%). Conclusions. The concordance of the results with the gold standard Myriad MyChoice CDx assay suggest the feasibility and reliability of HRD testing in diagnostic laboratories with high-throughput NGS platforms and qualified personnel.},\n\tlanguage = {en},\n\turldate = {2022-10-25},\n\tjournal = {Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology},\n\tauthor = {Fumagalli, Caterina and Betella, Ilaria and Ranghiero, Alberto and Guerini-Rocco, Elena and Bonaldo, Giulio and Rappa, Alessandra and Vacirca, Davide and Colombo, Nicoletta and Barberis, Massimo},\n\tmonth = sep,\n\tyear = {2022},\n\tkeywords = {DDM, HRD, Myriad, NGS, genomic scar, homologous recombination deficiency, ovarian cancer},\n\tpages = {288--294},\n}\n\n

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\n \n\n \n \n \n \n \n \n Alternative academic approaches for testing homologous recombination deficiency in ovarian cancer in the MITO16A/MaNGO-OV2 trial.\n \n \n \n \n\n\n \n Capoluongo, E. D.; Pellegrino, B.; Arenare, L.; Califano, D.; Scambia, G.; Beltrame, L.; Serra, V.; Scaglione, G. L.; Spina, A.; Cecere, S. C.; De Cecio, R.; Normanno, N.; Colombo, N.; Lorusso, D.; Russo, D.; Nardelli, C.; D’Incalci, M.; Llop-Guevara, A.; Pisano, C.; Baldassarre, G.; Mezzanzanica, D.; Artioli, G.; Setaro, M.; Tasca, G.; Roma, C.; Campanini, N.; Cinieri, S.; Sergi, A.; Musolino, A.; Perrone, F.; Chiodini, P.; Marchini, S.; and Pignata, S.\n\n\n \n\n\n\n ESMO Open, 7(5): 100585. October 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Alternative$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{capoluongo_alternative_2022,\n\ttitle = {Alternative academic approaches for testing homologous recombination deficiency in ovarian cancer in the {MITO16A}/{MaNGO}-{OV2} trial},\n\tvolume = {7},\n\tissn = {2059-7029},\n\turl = {https://www.sciencedirect.com/science/article/pii/S2059702922002150},\n\tdoi = {10.1016/j.esmoop.2022.100585},\n\tabstract = {Background\nThe detection of homologous recombination deficiency (HRD) can identify patients who are more responsive to platinum and poly ADP ribose polymerase inhibitors (PARPi). MyChoice CDx (Myriad) is the most used HRD test in ovarian cancer (OC). However, some limitations of commercial tests exist, because of the high rate of inconclusive results, costs, and the impossibility of evaluating functional resistance mechanisms.\nPatients and methods\nTwo academic genomic tests and a functional assay, the RAD51 foci, were evaluated to detect HRD. One hundred patients with high-grade OC enrolled in the MITO16A/MaNGO-OV2 trial and treated with first-line therapy with carboplatin, paclitaxel, and bevacizumab were analyzed.\nResults\nThe failure rate of the two genomic assays was 2\\%. The sensitivity in detecting HRD when compared with Myriad was 98.1\\% and 90.6\\%, respectively. The agreement rate with Myriad was 0.92 and 0.87, with a Cohen’s κ coefficient corresponding to 0.84 and 0.74, respectively. For the RAD51 foci assay, the failure rate was 30\\%. When the test was successful, discordant results for deficient and proficient tumors were observed, and additional HRD patients were identified compared to Myriad; sensitivity was 82.9\\%, agreement rate was 0.65, and Cohen’s κ coefficient was 0.18. The HRD detected by genomic assays and residual tumor at primary surgery and stage was correlated with progression-free survival at multivariate analysis.\nConclusions\nResults suggest the feasibility of academic tests for assessing HRD status that show robust concordance with Myriad and correlation with clinical outcome. The contribution of the functional information related to the RAD51 foci test to the genomic data needs further investigation.},\n\tlanguage = {en},\n\tnumber = {5},\n\turldate = {2022-10-25},\n\tjournal = {ESMO Open},\n\tauthor = {Capoluongo, E. D. and Pellegrino, B. and Arenare, L. and Califano, D. and Scambia, G. and Beltrame, L. and Serra, V. and Scaglione, G. L. and Spina, A. and Cecere, S. C. and De Cecio, R. and Normanno, N. and Colombo, N. and Lorusso, D. and Russo, D. and Nardelli, C. and D’Incalci, M. and Llop-Guevara, A. and Pisano, C. and Baldassarre, G. and Mezzanzanica, D. and Artioli, G. and Setaro, M. and Tasca, G. and Roma, C. and Campanini, N. and Cinieri, S. and Sergi, A. and Musolino, A. and Perrone, F. and Chiodini, P. and Marchini, S. and Pignata, S.},\n\tmonth = oct,\n\tyear = {2022},\n\tkeywords = {BRCA1, BRCA2, DDM, HRD, HRR, Myriad, RAD51, ovarian cancer},\n\tpages = {100585},\n}\n\n

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\n \n\n \n \n \n \n \n \n Detailed prenatal and postnatal MRI findings and clinical analysis of RAF1 in Noonan syndrome.\n \n \n \n \n\n\n \n Helenius, K.; Parkkola, R.; Arola, A.; Peltola, V.; and Haanpää, M. K.\n\n\n \n\n\n\n European Journal of Medical Genetics, 65(11): 104626. September 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Detailed$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{helenius_detailed_2022,\n\ttitle = {Detailed prenatal and postnatal {MRI} findings and clinical analysis of {RAF1} in {Noonan} syndrome},\n\tvolume = {65},\n\tissn = {1769-7212},\n\turl = {https://www.sciencedirect.com/science/article/pii/S1769721222002075},\n\tdoi = {10.1016/j.ejmg.2022.104626},\n\tabstract = {Noonan syndrome is a genetically heterogeneous developmental disorder, which usually includes findings such as short stature, facial dysmorphia, cardiac abnormalities and a varying degree of intellectual disability. We present a unique case of a rare variant of Noonan syndrome in a very preterm female infant born at 28 + 4 gestational weeks, with abnormal radiological findings visible at fetal magnetic resonance imaging (MRI) and evolution of the brain lesions during infancy.},\n\tlanguage = {en},\n\tnumber = {11},\n\turldate = {2022-10-25},\n\tjournal = {European Journal of Medical Genetics},\n\tauthor = {Helenius, Kjell and Parkkola, Riitta and Arola, Anita and Peltola, Ville and Haanpää, Maria K.},\n\tmonth = sep,\n\tyear = {2022},\n\tkeywords = {Brain MRI, CES, DDM, NGS, Noonan syndrome},\n\tpages = {104626},\n}\n\n

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\n \n\n \n \n \n \n \n \n Increased Risk of Hereditary Prostate Cancer in Italian Families with Hereditary Breast and Ovarian Cancer Syndrome Harboring Mutations in BRCA and in Other Susceptibility Genes.\n \n \n \n \n\n\n \n D’Elia, G.; Caliendo, G.; Tzioni, M.; Albanese, L.; Passariello, L.; Molinari, A. M.; and Vietri, M. T.\n\n\n \n\n\n\n Genes, 13(10): 1692. September 2022.\n Number: 10 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Increased$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{delia_increased_2022,\n\ttitle = {Increased {Risk} of {Hereditary} {Prostate} {Cancer} in {Italian} {Families} with {Hereditary} {Breast} and {Ovarian} {Cancer} {Syndrome} {Harboring} {Mutations} in {BRCA} and in {Other} {Susceptibility} {Genes}},\n\tvolume = {13},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2073-4425},\n\turl = {https://www.mdpi.com/2073-4425/13/10/1692},\n\tdoi = {10.3390/genes13101692},\n\tabstract = {Hereditary prostate cancer (HPCa) has the highest heritability of any cancer in men. Interestingly, it occurs in several hereditary syndromes, including breast and ovarian cancer (HBOC) and Lynch syndrome (LS). Several gene mutations related to these syndromes have been identified as biomarkers in HPCa. The goal of this study was to screen for germline mutations in susceptibility genes by using a multigene panel, and to subsequently correlate the results with clinical and laboratory parameters. This was undertaken in 180 HBOC families, which included 217 males with prostate cancer (PCa). Mutational analysis was further extended to 104 family members of mutated patients. Screening of HBOC families revealed that 30.5\\% harbored germline mutations in susceptibility genes, with 21.6\\% harboring pathogenic variants (PVs) and 8.9\\% having variants of uncertain significance (VUS). We found PVs at similar frequency in BRCA1 and BRCA2 genes (8.8\\% and 9.4\\%, respectively), while 0.56\\% of PVs were present in well-established susceptibility genes PALB2, TP53 and RAD51C. Moreover, 0.56\\% of monoallelic PVs were present in MUTYH, a gene whose function in tumorigenesis in the context of PCa is still unclear. Finally, we reported double heterozygosity (DH) in BRCA1/2 genes in a single family, and found double mutation (DM) present in BRCA2 in a separate family. There was no significant difference between the mean age of onset of PCa in HBOC families with or without germline mutations in susceptibility genes, while the mean survival was highest in mutated patients compared to wild type. Furthermore, PCa is the second most recurrent cancer in our cohort, resulting in 18\\% of cases in both mutated and non-mutated families. Our investigation shows that PVs were located mostly in the 3′ of BRCA1 and BRCA2 genes, and in BRCA2, most PVs fell in exon 11, suggesting a mutation cluster region relating to risk of HPCa. A total of 65 family members inherited the proband’s mutation; of these, 24 developed cancer, with 41 remaining unaffected.},\n\tlanguage = {en},\n\tnumber = {10},\n\turldate = {2022-10-25},\n\tjournal = {Genes},\n\tauthor = {D’Elia, Giovanna and Caliendo, Gemma and Tzioni, Maria-Myrsini and Albanese, Luisa and Passariello, Luana and Molinari, Anna Maria and Vietri, Maria Teresa},\n\tmonth = sep,\n\tyear = {2022},\n\tnote = {Number: 10\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {BRCA1, BRCA2, HBOC, HCS, PALB2, RAD51C, TP53, hereditary prostate cancer, susceptibility genes},\n\tpages = {1692},\n}\n\n

\n\n\n

\n Hereditary prostate cancer (HPCa) has the highest heritability of any cancer in men. Interestingly, it occurs in several hereditary syndromes, including breast and ovarian cancer (HBOC) and Lynch syndrome (LS). Several gene mutations related to these syndromes have been identified as biomarkers in HPCa. The goal of this study was to screen for germline mutations in susceptibility genes by using a multigene panel, and to subsequently correlate the results with clinical and laboratory parameters. This was undertaken in 180 HBOC families, which included 217 males with prostate cancer (PCa). Mutational analysis was further extended to 104 family members of mutated patients. Screening of HBOC families revealed that 30.5% harbored germline mutations in susceptibility genes, with 21.6% harboring pathogenic variants (PVs) and 8.9% having variants of uncertain significance (VUS). We found PVs at similar frequency in BRCA1 and BRCA2 genes (8.8% and 9.4%, respectively), while 0.56% of PVs were present in well-established susceptibility genes PALB2, TP53 and RAD51C. Moreover, 0.56% of monoallelic PVs were present in MUTYH, a gene whose function in tumorigenesis in the context of PCa is still unclear. Finally, we reported double heterozygosity (DH) in BRCA1/2 genes in a single family, and found double mutation (DM) present in BRCA2 in a separate family. There was no significant difference between the mean age of onset of PCa in HBOC families with or without germline mutations in susceptibility genes, while the mean survival was highest in mutated patients compared to wild type. Furthermore, PCa is the second most recurrent cancer in our cohort, resulting in 18% of cases in both mutated and non-mutated families. Our investigation shows that PVs were located mostly in the 3′ of BRCA1 and BRCA2 genes, and in BRCA2, most PVs fell in exon 11, suggesting a mutation cluster region relating to risk of HPCa. A total of 65 family members inherited the proband’s mutation; of these, 24 developed cancer, with 41 remaining unaffected.\n

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\n \n\n \n \n \n \n \n \n EGFR Mutations and PD-L1 Expression in Early-Stage Non-Small Cell Lung Cancer: A Real-World Data From a Single Center in Brazil.\n \n \n \n \n\n\n \n Alves Pinto, I.; de Oliveira Cavagna, R.; Virginio da Silva, A. L.; Dias, J. M.; Santana, I. V.; Souza, L. C.; Ferreira da Silva, F. A.; Biazotto Fernandes, M. F.; Junqueira Pinto, G. D.; Negreiros, I. S.; Santiago Gonçalves, M. F.; de Paula, F. E.; Berardinelli, G. N.; Casagrande, G. M. S.; Oliveira da Silva, M.; Albino da Silva, E. C.; de Oliveira, M. A.; Jacinto, A. A.; Duval da Silva, V.; Reis, R. M.; De Marchi, P.; and Leal, L. F.\n\n\n \n\n\n\n The Oncologist,oyac167. September 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"EGFR$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{alves_pinto_egfr_2022,\n\ttitle = {{EGFR} {Mutations} and {PD}-{L1} {Expression} in {Early}-{Stage} {Non}-{Small} {Cell} {Lung} {Cancer}: {A} {Real}-{World} {Data} {From} a {Single} {Center} in {Brazil}},\n\tissn = {1083-7159},\n\tshorttitle = {{EGFR} {Mutations} and {PD}-{L1} {Expression} in {Early}-{Stage} {Non}-{Small} {Cell} {Lung} {Cancer}},\n\turl = {https://doi.org/10.1093/oncolo/oyac167},\n\tdoi = {10.1093/oncolo/oyac167},\n\tabstract = {Targeted and immunotherapies are currently moving toward early-stage settings for patients with non-small cell lung cancer (NSCLC). Predictive biomarkers data are scarce in this scenario. We aimed to describe the frequency of EGFR mutations and PD-L1 expression levels in early-stage non-squamous patients with NSCLC from a large, single Brazilian oncology center.We retrospectively evaluated patients with NSCLC diagnosed at an early-stage (IB to IIIA-AJCC seventh edition) at Barretos Cancer Hospital (n = 302). EGFR mutational status was assessed in FFPE tumor tissues using distinct methodologies (NGS, Cobas, or Sanger sequencing). PD-L1 expression was evaluated by immunohistochemistry (clone 22C3) and reported as Tumor Proportion Score (TPS), categorized as \\&lt;1\\%, 1-49\\%, and ≥50\\%. We evaluated the association between EGFR mutational status and PD-L1 expression with sociodemographic and clinicopathological parameters by Fisher’s test, qui-square test, and logistic regression. Survival analysis was assessed by the Kaplan-Meier method and Cox regression model.EGFR mutations were detected in 17.3\\% (n = 48) of cases and were associated with female sex, never smokers, and longer overall and event-free survival. PD-L1 positivity was observed in 36.7\\% (n = 69) of cases [TPS 1-49\\% n = 44(23.4\\%); TPS ≥50\\% n = 25(13.3\\%)]. PD-L1 positivity was associated with smoking, weight loss, and higher disease stages (IIB/IIIA).The frequencies of EGFR mutations and PD-L1 positivity were described for early-stage non-squamous patients with NSCLC. These results will be essential for guiding treatment strategies with the recent approvals of osimertinib and immunotherapy in the adjuvant setting.},\n\turldate = {2022-10-25},\n\tjournal = {The Oncologist},\n\tauthor = {Alves Pinto, Icaro and de Oliveira Cavagna, Rodrigo and Virginio da Silva, Aline Larissa and Dias, Josiane Mourão and Santana, Iara Vidigal and Souza, Laísa Caroline and Ferreira da Silva, Flávio Augusto and Biazotto Fernandes, Maria Fernanda and Junqueira Pinto, Gustavo Dix and Negreiros, Izabella Santos and Santiago Gonçalves, Maria Fernanda and de Paula, Flávia Escremim and Berardinelli, Gustavo Nóriz and Casagrande, Giovanna Maria Stanfoca and Oliveira da Silva, Marcela and Albino da Silva, Eduardo Caetano and de Oliveira, Marco Antonio and Jacinto, Alexandre Arthur and Duval da Silva, Vinicius and Reis, Rui Manuel and De Marchi, Pedro and Leal, Letícia Ferro},\n\tmonth = sep,\n\tyear = {2022},\n\tkeywords = {DDM, DDM v5.4.2.5., EGFR, FFPE, NGS, NSCLC},\n\tpages = {oyac167},\n}\n\n

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\n \n\n \n \n \n \n \n \n Coinheritance of pathogenic variants in ATM and BRCA2 in families with multiple cancers: a case series.\n \n \n \n \n\n\n \n Freire, M. V.; Martin, M.; Segers, K.; Sepulchre, E.; Leroi, N.; Kalantari, H.; Wolter, P.; Collignon, J.; Polus, M.; Plomteux, O.; Josse, C.; and Bours, V.\n\n\n \n\n\n\n Technical Report In Review, September 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Coinheritance$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@techreport{freire_coinheritance_2022,\n\ttype = {preprint},\n\ttitle = {Coinheritance of pathogenic variants in {ATM} and {BRCA2} in families with multiple cancers: a case series},\n\tshorttitle = {Coinheritance of pathogenic variants in {ATM} and {BRCA2} in families with multiple cancers},\n\turl = {https://www.researchsquare.com/article/rs-2112256/v1},\n\tabstract = {Purpose. Pathogenic variants (PVs) in BRCA2 and ATMgenes have been linked to an increased risk of various cancers. BRCA2and ATM are part of the homologous recombination pathway, but the tumor risk in patients with simultaneous PVs in both genes remains largely unknown. In this study we describe four patients from three families with multiple cancers who coinherited PVs in BRCA2 and ATM genes.\nMethods. PVs in the patients were identified using NGS sequencing of the DNA and were confirmed by Sanger sequencing.\nResults. The first family included a 67-year-old male with kidney, prostate, and pancreatic adenocarcinomas, and his daughter diagnosed with breast cancer at 29 years. In the second family, a 28year-old female had breast cancer, while a male from the third family was diagnosed with prostate cancer at the age of 49, gastric cancer one year later and pancreatic cancer at 64. The three identified BRCA2 PVs were nonsense variants previously described as pathogenic, leading to a severely truncated or absent protein due to nonsense-mediated mRNA decay. Two of the ATM variants were previously reported as pathogenic, while the third one affects a conserved splice site.\nConclusions. The early age of diagnosis and the development of multiple cancers in the reported patients indicate a very high risk of cancer in double heterozygous patients, carrying PVs in the BRCA2 and ATM genes.},\n\tlanguage = {en},\n\turldate = {2022-10-25},\n\tinstitution = {In Review},\n\tauthor = {Freire, Maria Valeria and Martin, Marie and Segers, Karin and Sepulchre, Edith and Leroi, Natacha and Kalantari, Hassan and Wolter, Pascal and Collignon, Joëlle and Polus, Marc and Plomteux, Olivier and Josse, Claire and Bours, Vincent},\n\tmonth = sep,\n\tyear = {2022},\n\tdoi = {10.21203/rs.3.rs-2112256/v1},\n\tkeywords = {ATM, BRCA2, HCS},\n}\n\n

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\n \n\n \n \n \n \n \n \n Genetic analysis of a rare form of dyslipidemia: De novo ABCG5/APOB mutations in Greece.\n \n \n \n \n\n\n \n Koniari, E.; Skouma, A.; and Chrousos, G.\n\n\n \n\n\n\n Atherosclerosis, 355: 145. August 2022.\n Publisher: Elsevier\n\n\n\n
\n\n\n\n \n \n $\"Genetic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{koniari_genetic_2022,\n\ttitle = {Genetic analysis of a rare form of dyslipidemia: {De} novo {ABCG5}/{APOB} mutations in {Greece}},\n\tvolume = {355},\n\tissn = {0021-9150, 1879-1484},\n\tshorttitle = {Genetic analysis of a rare form of dyslipidemia},\n\turl = {https://www.atherosclerosis-journal.com/article/S0021-9150(22)00932-7/fulltext},\n\tdoi = {10.1016/j.atherosclerosis.2022.06.645},\n\tlanguage = {English},\n\turldate = {2022-10-25},\n\tjournal = {Atherosclerosis},\n\tauthor = {Koniari, E. and Skouma, A. and Chrousos, G.},\n\tmonth = aug,\n\tyear = {2022},\n\tnote = {Publisher: Elsevier},\n\tkeywords = {ABCG5, ABCG5/APOB, APOB, DDM, NGS},\n\tpages = {145},\n}\n\n

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\n \n\n \n \n \n \n \n \n Chylomicron retention disease: A case report in Greece.\n \n \n \n \n\n\n \n Koniari, E.; Skouma, A.; Sariklaki, M.; Vasilogiannakis, G.; Maniadaki, I.; Papadopoulou, E.; and Chrousos, G.\n\n\n \n\n\n\n Atherosclerosis, 355: 45. August 2022.\n Publisher: Elsevier\n\n\n\n
\n\n\n\n \n \n $\"Chylomicron$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{koniari_chylomicron_2022,\n\ttitle = {Chylomicron retention disease: {A} case report in {Greece}},\n\tvolume = {355},\n\tissn = {0021-9150, 1879-1484},\n\tshorttitle = {Chylomicron retention disease},\n\turl = {https://www.atherosclerosis-journal.com/article/S0021-9150(22)00502-0/fulltext},\n\tdoi = {10.1016/j.atherosclerosis.2022.06.215},\n\tlanguage = {English},\n\turldate = {2022-10-25},\n\tjournal = {Atherosclerosis},\n\tauthor = {Koniari, E. and Skouma, A. and Sariklaki, M. and Vasilogiannakis, G. and Maniadaki, I. and Papadopoulou, E. and Chrousos, G.},\n\tmonth = aug,\n\tyear = {2022},\n\tnote = {Publisher: Elsevier},\n\tkeywords = {CRD, DDM, NGS, SAR1B},\n\tpages = {45},\n}\n\n

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\n \n\n \n \n \n \n \n \n Age-dependent association of clonal hematopoiesis with COVID-19 mortality in patients over 60 years.\n \n \n \n \n\n\n \n Del Pozo-Valero, M.; Corton, M.; López-Rodríguez, R.; Mahillo-Fernández, I.; Ruiz-Hornillos, J.; Minguez, P.; Villaverde, C.; Pérez-Tomás, M. E.; Barreda-Sánchez, M.; Mancebo, E.; Fernández-Caballero, L.; Sanchez, R. F.; Vara, I. G.; Gordo, L. M.; Martínez-Ramas, A.; Ondo, L.; Romero, R.; Górgolas, M.; Cabello, A.; Barba, G. P.; Heili, S.; Calvo, C.; Santos, A.; Ríos, M. D. M.; Sánchez-Pernaute, O.; Llanos, L.; Zazo, S.; Rojo, F.; Villar, F.; de Andrés, R.; Alfaro, I. J.; Gadea, I.; Perales, C.; Herrero, A.; Taracido, J. C.; García-Vázquez, E.; Jara-Rubio, R.; Pons-Miñano, J. A.; Marín-Martínez, J. M.; Herranz-Marín, M. T.; Bernal-Morell, E.; García-García, J.; de Dios González-Caballero, J.; Chirlaque-López, M. D.; Minguela-Puras, A.; Muro-Amador, M.; Moreno-Docón, A.; Yagüe-Guirao, G.; Abellán-Perpiñán, J. M.; Martínez-Pérez, J. E.; Sánchez-Martínez, F. I.; Utrero-Rico, A.; Fernández-Ruiz, M.; Carretero, O.; Aguado, J. M.; Laguna-Goya, R.; Juárez, Y. C.; Jiménez, Á.; Abián, M. H.; Salmones, M. G.; Alarcon, L. G.; Oliveira, M. R.; Romero, C. F. C.; Cosgaya, C. A.; Palomares, V. V.; Rodríguez, L. G.; Abad, M. S. C.; Torrejón, M. C. G.; Paz-Artal, E.; Guillén-Navarro, E.; Almoguera, B.; Ayuso, C.; and the STOP_Coronavirus Study Group\n\n\n \n\n\n\n GeroScience. October 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Age-dependent$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{del_pozo-valero_age-dependent_2022,\n\ttitle = {Age-dependent association of clonal hematopoiesis with {COVID}-19 mortality in patients over 60 years},\n\tissn = {2509-2723},\n\turl = {https://doi.org/10.1007/s11357-022-00666-5},\n\tdoi = {10.1007/s11357-022-00666-5},\n\tabstract = {Clonal hematopoiesis, especially that of indeterminate potential (CHIP), has been associated with age-related diseases, such as those contributing to a more severe COVID-19. Four studies have attempted to associate CHIP with COVID-19 severity without conclusive findings. In the present work, we explore the association between CHIP and COVID-19 mortality. Genomic DNA extracted from peripheral blood of COVID-19 patients (n = 241 deceased, n = 239 survivors) was sequenced with the Myeloid Solutions™ panel of SOPHiA Genetics. The association between clonality and age and clonality and mortality was studied using logistic regression models adjusted for sex, ethnicity, and comorbidities. The association with mortality was performed with patients stratified into four groups of age according to the quartiles of the distribution: 60–74 years, 75–84 years, 85–91 years, and 92–101 years. Clonality was found in 38\\% of the cohort. The presence of CHIP variants, but not the number, significantly increased with age in the entire cohort of COVID-19 patients, as well as in the group of survivors (p {\\textless} 0.001). When patients were stratified by age and the analysis adjusted, CHIP classified as pathogenic/likely pathogenic was significantly more represented in deceased patients compared with survivors in the group of 75–84 years (34.6\\% vs 13.7\\%, p = 0.020). We confirmed the well-established linear relationship between age and clonality in the cohort of COVID-19 patients and found a significant association between pathogenic/likely pathogenic CHIP and mortality in patients from 75 to 84 years that needs to be further validated.},\n\tlanguage = {en},\n\turldate = {2022-10-25},\n\tjournal = {GeroScience},\n\tauthor = {Del Pozo-Valero, Marta and Corton, Marta and López-Rodríguez, Rosario and Mahillo-Fernández, Ignacio and Ruiz-Hornillos, Javier and Minguez, Pablo and Villaverde, Cristina and Pérez-Tomás, María Elena and Barreda-Sánchez, María and Mancebo, Esther and Fernández-Caballero, Lidia and Sanchez, Ruth Fernández and Vara, Inés García and Gordo, Laura Marzal and Martínez-Ramas, Andrea and Ondo, Lorena and Romero, Raquel and Górgolas, Miguel and Cabello, Alfonso and Barba, Germán Peces and Heili, Sara and Calvo, César and Santos, Arnoldo and Ríos, María Dolores Martín and Sánchez-Pernaute, Olga and Llanos, Lucía and Zazo, Sandra and Rojo, Federico and Villar, Felipe and de Andrés, Raimundo and Alfaro, Ignacio Jiménez and Gadea, Ignacio and Perales, Celia and Herrero, Antonio and Taracido, Juan Carlos and García-Vázquez, Elisa and Jara-Rubio, Rubén and Pons-Miñano, José A. and Marín-Martínez, Juana María and Herranz-Marín, María Teresa and Bernal-Morell, Enrique and García-García, Josefina and de Dios González-Caballero, Juan and Chirlaque-López, María Dolores and Minguela-Puras, Alfredo and Muro-Amador, Manuel and Moreno-Docón, Antonio and Yagüe-Guirao, Genoveva and Abellán-Perpiñán, José M. and Martínez-Pérez, Jorge E. and Sánchez-Martínez, Fernando I. and Utrero-Rico, Alberto and Fernández-Ruiz, Mario and Carretero, Octavio and Aguado, José María and Laguna-Goya, Rocío and Juárez, Yolanda Cañadas and Jiménez, Ángel and Abián, María Herrera and Salmones, Mercedes García and Alarcon, Lidia Gagliardi and Oliveira, María Rubio and Romero, Carlos Fabian Castaño and Cosgaya, Carlos Aranda and Palomares, Virginia Víctor and Rodríguez, Leticia García and Abad, María Sánchez Carpintero and Torrejón, María Carmen García and Paz-Artal, Estela and Guillén-Navarro, Encarna and Almoguera, Berta and Ayuso, Carmen and {the STOP\\_Coronavirus Study Group}},\n\tmonth = oct,\n\tyear = {2022},\n\tkeywords = {COVID-19, Clonal variants, DDM, MYS, Mortality risk},\n}\n\n

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\n \n\n \n \n \n \n \n \n 579P A multicenter evaluation of a low pass whole genome sequencing-based solution for homologous recombination deficiency detection.\n \n \n \n \n\n\n \n Buisson, A.; Saintigny, P.; Pujade-Lauraine, E.; Montoto Grillot, C.; Varcica, D.; Barberis, M.; Colombo, N.; Harlé, A.; Gilson, P.; Roma, C.; Bergantino, F.; Harter, P.; Pignata, S.; Gonzalez Martin, A.; Schauer, C.; Fujiwara, K.; Vergote, I.; Juhler-Nottrup, T.; Just, P.; and Ray-Coquard, I.\n\n\n \n\n\n\n Annals of Oncology, 33: S811–S812. September 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"579P$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{buisson_579p_2022,\n\ttitle = {{579P} {A} multicenter evaluation of a low pass whole genome sequencing-based solution for homologous recombination deficiency detection},\n\tvolume = {33},\n\tissn = {09237534},\n\turl = {https://linkinghub.elsevier.com/retrieve/pii/S0923753422025583},\n\tdoi = {10.1016/j.annonc.2022.07.707},\n\tabstract = {Background: The iPocc randomised multicentre international study reported improved progression-free survival (PFS) but not overall survival (OS) with IP carboplatin and IV paclitaxel vs IV chemotherapy (chemo) in patients (pts) with epithelial ovarian, fallopian tube or primary peritoneal cancer. Previous studies suggested that pts with BRCA-deﬁcient tumours may beneﬁt from IP chemo. We conducted a nonprespeciﬁed analysis of the prognostic and predictive value of HRD in tissue samples retrospectively obtained from iPocc trial pts.\nMethods: 166 pts from participating centres in Singapore and Japan had adequate tissue for next-generation sequencing with ACT Genomics ACTOncoÒ+. HRD was deﬁned by high loss of heterozygosity at a threshold of {\\textgreater}¼0.35 (LOH high) or presence of a pathogenic BRCA mutation (BRCAmt). Median PFS and OS were estimated using Kaplan-Meier method. Fisher’s exact and Student’s t-test were used to compare group characteristics.\nResults: Both IP and IV arms had similar frequencies of BRCAmt, homologous recombination repair pathway mutations (HRRmt) and LOH high. All BRCAmt tumours were LOH high. There were no differences in PFS or OS in IP vs IV arms in this cohort. Outcome data based on HRD subgroups are summarised in the table. In the overall group, LOH high was associated with improved OS (HR 0.43, p¼.001) but not PFS (HR 1.04, p¼.87). BRCAmt pts showed a trend towards improved OS (HR 0.68, p¼.24) and PFS (HR 0.73, p¼.32). HRRmt status did not signiﬁcantly affect OS (HR 0.95, p¼.84) or PFS (HR 1.21, p¼.30). Table: 577P Outcomes of IP vs IV arms based on BRCA, HRR and HRD (based on LOH {\\textgreater}[ 0.35) status IP vs IV chemo Frequency Median PFS HR p Median OS HR p (months) (months) BRCAmt n¼16 (9.6\\%) 25.7 vs 23.8 0.83 .73 94.5 vs 85.3 0.90 .90 BRCAwt n¼150 (90.4\\%) 22.1 vs 22.8 1.07 .72 60.1 vs 77.1 1.18 .44 LOH high n¼135 (81.3\\%) 23.5 vs 23.4 1.00 .98 73.0 vs 85.3 1.21 .42 LOH low n¼31 (18.7\\%) 9.2 vs 17.2 1.20 .71 29.4 vs 33.2 1.00 .996 HRRmt n¼109 (65.7\\%) 20.7 vs 23.3 1.15 .50 65.8 vs 85.3 1.25 .39 HRRwt n¼57 (34.3\\%) 25.0 vs 20.1 0.98 .95 57.2 vs 65.2 1.09 .81\nConclusions: In this small subgroup analysis of iPocc pts, BRCAmt pts demonstrated a trend towards improved PFS and OS with IP compared with IV chemo. BRCAmt and LOH high, but not HRRmt, correlated with improved outcomes in the overall group. Larger prospective studies with integrated molecular analyses are needed to better deﬁne the impact of HRD in IP vs IV chemo.},\n\tlanguage = {en},\n\turldate = {2022-10-25},\n\tjournal = {Annals of Oncology},\n\tauthor = {Buisson, A. and Saintigny, P. and Pujade-Lauraine, E. and Montoto Grillot, C. and Varcica, D. and Barberis, M. and Colombo, N. and Harlé, A. and Gilson, P. and Roma, C. and Bergantino, F. and Harter, P. and Pignata, S. and Gonzalez Martin, A.J. and Schauer, C. and Fujiwara, K. and Vergote, I.B. and Juhler-Nottrup, T.J. and Just, P-A. and Ray-Coquard, I.L.},\n\tmonth = sep,\n\tyear = {2022},\n\tkeywords = {BRCA1, BRCA1/2, BRCA2, DDM, HRD, NGS},\n\tpages = {S811--S812},\n}\n\n

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\n Background: The iPocc randomised multicentre international study reported improved progression-free survival (PFS) but not overall survival (OS) with IP carboplatin and IV paclitaxel vs IV chemotherapy (chemo) in patients (pts) with epithelial ovarian, fallopian tube or primary peritoneal cancer. Previous studies suggested that pts with BRCA-deﬁcient tumours may beneﬁt from IP chemo. We conducted a nonprespeciﬁed analysis of the prognostic and predictive value of HRD in tissue samples retrospectively obtained from iPocc trial pts. Methods: 166 pts from participating centres in Singapore and Japan had adequate tissue for next-generation sequencing with ACT Genomics ACTOncoÒ+. HRD was deﬁned by high loss of heterozygosity at a threshold of \\textgreater¼0.35 (LOH high) or presence of a pathogenic BRCA mutation (BRCAmt). Median PFS and OS were estimated using Kaplan-Meier method. Fisher’s exact and Student’s t-test were used to compare group characteristics. Results: Both IP and IV arms had similar frequencies of BRCAmt, homologous recombination repair pathway mutations (HRRmt) and LOH high. All BRCAmt tumours were LOH high. There were no differences in PFS or OS in IP vs IV arms in this cohort. Outcome data based on HRD subgroups are summarised in the table. In the overall group, LOH high was associated with improved OS (HR 0.43, p¼.001) but not PFS (HR 1.04, p¼.87). BRCAmt pts showed a trend towards improved OS (HR 0.68, p¼.24) and PFS (HR 0.73, p¼.32). HRRmt status did not signiﬁcantly affect OS (HR 0.95, p¼.84) or PFS (HR 1.21, p¼.30). Table: 577P Outcomes of IP vs IV arms based on BRCA, HRR and HRD (based on LOH \\textgreater[ 0.35) status IP vs IV chemo Frequency Median PFS HR p Median OS HR p (months) (months) BRCAmt n¼16 (9.6%) 25.7 vs 23.8 0.83 .73 94.5 vs 85.3 0.90 .90 BRCAwt n¼150 (90.4%) 22.1 vs 22.8 1.07 .72 60.1 vs 77.1 1.18 .44 LOH high n¼135 (81.3%) 23.5 vs 23.4 1.00 .98 73.0 vs 85.3 1.21 .42 LOH low n¼31 (18.7%) 9.2 vs 17.2 1.20 .71 29.4 vs 33.2 1.00 .996 HRRmt n¼109 (65.7%) 20.7 vs 23.3 1.15 .50 65.8 vs 85.3 1.25 .39 HRRwt n¼57 (34.3%) 25.0 vs 20.1 0.98 .95 57.2 vs 65.2 1.09 .81 Conclusions: In this small subgroup analysis of iPocc pts, BRCAmt pts demonstrated a trend towards improved PFS and OS with IP compared with IV chemo. BRCAmt and LOH high, but not HRRmt, correlated with improved outcomes in the overall group. Larger prospective studies with integrated molecular analyses are needed to better deﬁne the impact of HRD in IP vs IV chemo.\n

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\n \n\n \n \n \n \n \n \n Chromothripsis is a frequent event and underlies typical genetic changes in early T-cell precursor lymphoblastic leukemia in adults.\n \n \n \n \n\n\n \n Arniani, S.; Pierini, V.; Pellanera, F.; Matteucci, C.; Di Giacomo, D.; Bardelli, V.; Quintini, M.; Mavridou, E.; Lema Fernandez, A. G.; Nardelli, C.; Moretti, M.; Gorello, P.; Crescenzi, B.; Romoli, S.; Beacci, D.; Cerrano, M.; Fracchiolla, N.; Sica, S.; Forghieri, F.; Giglio, F.; Dargenio, M.; Elia, L.; La Starza, R.; and Mecucci, C.\n\n\n \n\n\n\n Leukemia,1–9. August 2022.\n Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"Chromothripsis$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{arniani_chromothripsis_2022,\n\ttitle = {Chromothripsis is a frequent event and underlies typical genetic changes in early {T}-cell precursor lymphoblastic leukemia in adults},\n\tcopyright = {2022 The Author(s)},\n\tissn = {1476-5551},\n\turl = {https://www.nature.com/articles/s41375-022-01671-5},\n\tdoi = {10.1038/s41375-022-01671-5},\n\tabstract = {Chromothripsis is a mitotic catastrophe that arises from multiple double strand breaks and incorrect re-joining of one or a few chromosomes. We report on incidence, distribution, and features of chromothriptic events in T-cell acute lymphoblastic leukemias (T-ALL). SNP array was performed in 103 T-ALL (39 ETP/near ETP, 59 non-ETP, and 5 with unknown stage of differentiation), including 38 children and 65 adults. Chromothripsis was detected in 11.6\\% of all T-ALL and occurred only in adult cases with an immature phenotype (12/39 cases; 30\\%). It affected 1 to 4 chromosomes, and recurrently involved chromosomes 1, 6, 7, and 17. Abnormalities of genes typically associated with T-ALL were found at breakpoints of chromothripsis. In addition, it gave rise to new/rare alterations, such as, the SFPQ::ZFP36L2 fusion, reported in pediatric T-ALL, deletions of putative suppressors, such as IKZF2 and CSMD1, and amplification of the BCL2 gene. Compared to negative cases, chromothripsis positive T-ALL had a significantly higher level of MYCN expression, and a significant downregulation of RGCC, which is typically induced by TP53 in response to DNA damage. Furthermore we identified mutations and/or deletions of DNA repair/genome stability genes in all cases, and an association with NUP214 rearrangements in 33\\% of cases.},\n\tlanguage = {en},\n\turldate = {2022-10-18},\n\tjournal = {Leukemia},\n\tauthor = {Arniani, Silvia and Pierini, Valentina and Pellanera, Fabrizia and Matteucci, Caterina and Di Giacomo, Danika and Bardelli, Valentina and Quintini, Martina and Mavridou, Elena and Lema Fernandez, Anair Graciela and Nardelli, Carlotta and Moretti, Martina and Gorello, Paolo and Crescenzi, Barbara and Romoli, Silvia and Beacci, Donatella and Cerrano, Marco and Fracchiolla, Nicola and Sica, Simona and Forghieri, Fabio and Giglio, Fabio and Dargenio, Michela and Elia, Loredana and La Starza, Roberta and Mecucci, Cristina},\n\tmonth = aug,\n\tyear = {2022},\n\tnote = {Publisher: Nature Publishing Group},\n\tkeywords = {Acute lymphocytic leukaemia, HCS, Hereditary Cancer Solution, Leukaemia, MYS, Myeloid Solution},\n\tpages = {1--9},\n}\n\n

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\n \n\n \n \n \n \n \n \n Corrected Allele Frequency of BRCA1/2 Mutations Is an Independent Prognostic Factor for Treatment Response to PARP-Inhibitors in Ovarian Cancer Patients.\n \n \n \n \n\n\n \n Grech, C. T.; Pils, D.; Aust, S.; Grimm, C.; Polterauer, S.; Reinthaller, A.; Müllauer, L.; Reischer, T.; and Bekos, C.\n\n\n \n\n\n\n Journal of Personalized Medicine, 12(9): 1467. September 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Corrected$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{grech_corrected_2022,\n\ttitle = {Corrected {Allele} {Frequency} of {BRCA1}/2 {Mutations} {Is} an {Independent} {Prognostic} {Factor} for {Treatment} {Response} to {PARP}-{Inhibitors} in {Ovarian} {Cancer} {Patients}},\n\tvolume = {12},\n\tissn = {2075-4426},\n\turl = {https://www.mdpi.com/2075-4426/12/9/1467},\n\tdoi = {10.3390/jpm12091467},\n\tabstract = {PARP inhibitors (PARPi) have increased treatment options in ovarian cancer, particularly in patients with BRCA1/2 mutations, although there are still marked differences in the duration of patients’ response to this targeted therapy. BRCA testing is routinely performed in tumor tissue of ovarian cancer patients. The resulting molecular pathological ﬁndings include the genetic nomenclature of the mutation, the frequency of the mutated allele (variant allele frequency, VAF), and the tumor cell content. VAF measures the percentage of mutated alleles from the total alleles in the cells of the examined tissue. The aim of this study was to investigate the signiﬁcance of VAF on the therapeutic response to PARPis in ovarian cancer patients. Epithelial ovarian cancer patients harboring BRCA1/2 tumor mutations, who underwent germline testing and received PARPi therapy at the Medical University of Vienna (n = 41) were included in the study. Corrected VAF (cVAF) was calculated based on VAF, tumor cell content, and germline mutation. Patients were divided into two groups based on their cVAF. Median PFS under PARPi in patients with low cVAF was 13.0 months (IQR [10.3-not reached]) and was not reached in the high cVAF group. High cVAF was signiﬁcantly associated with longer PFS in the multivariate analysis (HR = 0.07; 95\\% CI [0.01–0.63]; p = 0.017). In conclusion, high cVAF was associated with a signiﬁcantly better response to PARPi in this study population.},\n\tlanguage = {en},\n\tnumber = {9},\n\turldate = {2022-10-18},\n\tjournal = {Journal of Personalized Medicine},\n\tauthor = {Grech, Christina T. and Pils, Dietmar and Aust, Stefanie and Grimm, Christoph and Polterauer, Stephan and Reinthaller, Alexander and Müllauer, Leonhard and Reischer, Theresa and Bekos, Christine},\n\tmonth = sep,\n\tyear = {2022},\n\tkeywords = {BRCA1, BRCA1/2, BRCA2, DDM},\n\tpages = {1467},\n}\n\n

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\n \n\n \n \n \n \n \n \n Breast Cancer Genetics: Diagnostics and Treatment.\n \n \n \n \n\n\n \n Criscitiello, C.; and Corti, C.\n\n\n \n\n\n\n Genes, 13(9): 1593. September 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Breast$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{criscitiello_breast_2022,\n\ttitle = {Breast {Cancer} {Genetics}: {Diagnostics} and {Treatment}},\n\tvolume = {13},\n\tissn = {2073-4425},\n\tshorttitle = {Breast {Cancer} {Genetics}},\n\turl = {https://www.mdpi.com/2073-4425/13/9/1593},\n\tdoi = {10.3390/genes13091593},\n\tabstract = {Breast cancer (BC) genetics has become a fundamental aspect of BC management [...]},\n\tlanguage = {en},\n\tnumber = {9},\n\turldate = {2022-10-18},\n\tjournal = {Genes},\n\tauthor = {Criscitiello, Carmen and Corti, Chiara},\n\tmonth = sep,\n\tyear = {2022},\n\tkeywords = {CNV, HCS indirectly, MLPA},\n\tpages = {1593},\n}\n\n

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\n \n\n \n \n \n \n \n \n Hb Kirikiriroa [α57(E6)Gly→Cys; HBA1: c.172G\\textgreaterT]: A Novel Unstable α-Globin Variant with Oxidized Derivatives Interfering with Hb A1c.\n \n \n \n \n\n\n \n Moore, J. A.; Pullon, B. M.; Wang, D.; Monaghan, J.; and Moore, H.\n\n\n \n\n\n\n Hemoglobin, 46(2): 81–86. August 2022.\n Publisher: Taylor & Francis _eprint: https://doi.org/10.1080/03630269.2022.2083971\n\n\n\n
\n\n\n\n \n \n $\"Hb$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{moore_hb_2022,\n\ttitle = {Hb {Kirikiriroa} [α57({E6}){Gly}→{Cys}; {HBA1}: c.{172G}{\\textgreater}{T}]: {A} {Novel} {Unstable} α-{Globin} {Variant} with {Oxidized} {Derivatives} {Interfering} with {Hb} {A1c}},\n\tvolume = {46},\n\tissn = {0363-0269},\n\tshorttitle = {Hb {Kirikiriroa} [α57({E6}){Gly}→{Cys}; {HBA1}},\n\turl = {https://doi.org/10.1080/03630269.2022.2083971},\n\tdoi = {10.1080/03630269.2022.2083971},\n\tabstract = {We report the identification of a novel hemoglobin (Hb) variant [α57(E6)Gly→Cys; HBA1: c.172G{\\textgreater}T], to be referred to as Hb Kirikiriroa. The variant was detected in five subjects from two families, with familial relationship established between the families following diagnosis. A persistently elevated Hb A1c over a 1-year period prompted hemoglobinopathy screening in an adolescent male of New Zealand (NZ) European descent (case 1). Capillary electrophoresis (CE) revealed the variant was negatively charged and susceptible to oxidation, with multiple abnormal peaks detected (0.4–5.1\\% total Hb). Hb A1c analysis by cation exchange high performance liquid chromatography (HPLC) was the first indication of the variant in a pregnant female of NZ European descent (case 2). Cases 1 and 2 had normal complete blood counts. Isopropanol stability testing provided evidence the variant was unstable. We herein describe the characterization of Hb Kirikiriroa and clinical significance of the variant for interference with Hb A1c analysis by CE and cation exchange HPLC.},\n\tnumber = {2},\n\turldate = {2022-10-17},\n\tjournal = {Hemoglobin},\n\tauthor = {Moore, Jordyn A. and Pullon, Beverley M. and Wang, Darrell and Monaghan, Julie and Moore, Helen},\n\tmonth = aug,\n\tyear = {2022},\n\tpmid = {35957560},\n\tnote = {Publisher: Taylor \\& Francis\n\\_eprint: https://doi.org/10.1080/03630269.2022.2083971},\n\tkeywords = {Alamut Visual v2.15, Capillary electrophoresis (CE), HBA1, Hb A1c, glycated hemoglobin (Hb A1c), high performance liquid chromatography (HPLC), time-of-flight (TOF) mass spectrometry (MS), unstable α-globin variant},\n\tpages = {81--86},\n}\n\n

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\n \n\n \n \n \n \n \n \n EZH2 mutations at diagnosis in follicular lymphoma: a promising biomarker to guide frontline treatment.\n \n \n \n \n\n\n \n Martínez-Laperche, C.; Sanz-Villanueva, L.; Díaz Crespo, F. J.; Muñiz, P.; Martín Rojas, R.; Carbonell, D.; Chicano, M.; Suárez-González, J.; Menárguez, J.; Kwon, M.; Diez Martín, J. L.; Buño, I.; and Bastos Oreiro, M.\n\n\n \n\n\n\n BMC Cancer, 22(1): 982. September 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"EZH2$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{martinez-laperche_ezh2_2022,\n\ttitle = {{EZH2} mutations at diagnosis in follicular lymphoma: a promising biomarker to guide frontline treatment},\n\tvolume = {22},\n\tissn = {1471-2407},\n\tshorttitle = {{EZH2} mutations at diagnosis in follicular lymphoma},\n\turl = {https://doi.org/10.1186/s12885-022-10070-z},\n\tdoi = {10.1186/s12885-022-10070-z},\n\tabstract = {EZH2 is mutated in nearly 25\\% of follicular lymphoma (FL) cases. Little is known about how EZH2 affects patients’ response to therapy. In this context, the aim of this study was to retrospectively analyze the frequency of mutations in EZH2 at diagnosis in tissue and ctDNA in patients with FL and to assess the patients’ outcomes after receiving immunochemotherapy, depending on the EZH2 mutation status. Among the 154 patients included in the study, 27\\% had mutated EZH2 (46\\% with high-grade and 26\\% with low-grade FL). Of the mutated tissue samples, the mutation in ctDNA was identified in 44\\% of cases. EZH2 mutation in ctDNA was not identified in any patient unmutated in the tissue.},\n\tnumber = {1},\n\turldate = {2022-10-18},\n\tjournal = {BMC Cancer},\n\tauthor = {Martínez-Laperche, C. and Sanz-Villanueva, L. and Díaz Crespo, F. J. and Muñiz, P. and Martín Rojas, R. and Carbonell, D. and Chicano, M. and Suárez-González, J. and Menárguez, J. and Kwon, M. and Diez Martín, J. L. and Buño, I. and Bastos Oreiro, M.},\n\tmonth = sep,\n\tyear = {2022},\n\tkeywords = {EZH2, Follicular lymphoma, Lymphoma solution, R-Bendamustine, R-CHOP},\n\tpages = {982},\n}\n\n

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\n \n\n \n \n \n \n \n \n Sirolimus treatment of a pten hamartoma tumor syndrome presenting with melena.\n \n \n \n \n\n\n \n Şahin, G. E.; Hoşnut, F. Ö.; Yeşil, Ş.; Lafcı, N. G.; Gül, A. E.; and Şahin, G.\n\n\n \n\n\n\n The Turkish Journal of Pediatrics, 64(4): 766. September 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Sirolimus$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{sahin_sirolimus_2022,\n\ttitle = {Sirolimus treatment of a pten hamartoma tumor syndrome presenting with melena},\n\tvolume = {64},\n\tissn = {0041-4301},\n\turl = {http://www.turkishjournalpediatrics.org/doi.php?doi=10.24953/turkjped.2021.5330},\n\tdoi = {10.24953/turkjped.2021.5330},\n\tabstract = {Background. PTEN hamartoma tumor syndrome (PHTS) is an umbrella term including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), PTEN-related Proteus syndrome (PS), and PTEN-related Proteus-like syndrome. One of the disorders in PHTS spectrum, CS is characterized by macrocephaly, mucocutaneous findings, gastrointestinal system (GIS) polyposis and an increased lifetime risk of GIS, breast, thyroid and other cancers.},\n\tlanguage = {en},\n\tnumber = {4},\n\turldate = {2022-10-18},\n\tjournal = {The Turkish Journal of Pediatrics},\n\tauthor = {Şahin, Gülseren Evirgen and Hoşnut, Ferda Özbay and Yeşil, Şule and Lafcı, Naz Güleray and Gül, Aylin Ege and Şahin, Gürses},\n\tmonth = sep,\n\tyear = {2022},\n\tkeywords = {DDM v.5.7.7, HCS, PHTS, PTEN hamartoma tumor syndrome},\n\tpages = {766},\n}\n\n

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\n \n\n \n \n \n \n \n \n Congenital Myasthenic Syndromes in Turkey: Clinical and Molecular Characterization of 16 Cases With Three Novel Mutations.\n \n \n \n \n\n\n \n Öztürk, S.; Güleç, A.; Erdoğan, M.; Demir, M.; Canpolat, M.; Gümüş, H.; Çağlayan, A. O.; Dündar, M.; and Per, H.\n\n\n \n\n\n\n Pediatric Neurology, 136: 43–49. August 2022.\n Publisher: Elsevier\n\n\n\n
\n\n\n\n \n \n $\"Congenital$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{ozturk_congenital_2022,\n\ttitle = {Congenital {Myasthenic} {Syndromes} in {Turkey}: {Clinical} and {Molecular} {Characterization} of 16 {Cases} {With} {Three} {Novel} {Mutations}},\n\tvolume = {136},\n\tissn = {0887-8994, 1873-5150},\n\tshorttitle = {Congenital {Myasthenic} {Syndromes} in {Turkey}},\n\turl = {https://www.pedneur.com/article/S0887-8994(22)00165-5/fulltext},\n\tdoi = {10.1016/j.pediatrneurol.2022.08.001},\n\tlanguage = {English},\n\turldate = {2022-10-18},\n\tjournal = {Pediatric Neurology},\n\tauthor = {Öztürk, Selcan and Güleç, Ayten and Erdoğan, Murat and Demir, Mikail and Canpolat, Mehmet and Gümüş, Hakan and Çağlayan, Ahmet Okay and Dündar, Munis and Per, Hüseyin},\n\tmonth = aug,\n\tyear = {2022},\n\tpmid = {36099689},\n\tnote = {Publisher: Elsevier},\n\tkeywords = {CHRNE, CMS, Congenital myasthenic syndrome, DDM v5.10.8, DOK7, Genetic diagnosis},\n\tpages = {43--49},\n}\n\n

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\n \n\n \n \n \n \n \n \n Cellular and molecular characterization of two novel asparagine synthetase gene mutations linked to asparagine synthetase deficiency.\n \n \n \n \n\n\n \n Staklinski, S. J.; Chang, M. C.; Yu, F.; Collins Ruff, K.; Franz, D. N.; Qian, Z.; Bloom, L. B.; Merritt, M. E.; McKenna, R.; and Kilberg, M. S.\n\n\n \n\n\n\n Journal of Biological Chemistry, 298(9): 102385. September 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Cellular$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{staklinski_cellular_2022,\n\ttitle = {Cellular and molecular characterization of two novel asparagine synthetase gene mutations linked to asparagine synthetase deficiency},\n\tvolume = {298},\n\tissn = {0021-9258},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0021925822008286},\n\tdoi = {10.1016/j.jbc.2022.102385},\n\tabstract = {Asparagine synthetase (ASNS) catalyzes synthesis of asparagine (Asn) and Glu from Asp and Gln in an ATP-dependent reaction. Asparagine synthetase deficiency (ASNSD) results from biallelic mutations in the ASNS gene. Affected children exhibit congenital microcephaly, continued brain atrophy, seizures, and often premature mortality. However, the underlying mechanisms are unclear. This report describes a compound heterozygotic ASNSD child with two novel mutations in the ASNS gene, c.1118G{\\textgreater}T (paternal) and c.1556G{\\textgreater}A (maternal), that lead to G373V or R519H ASNS variants. Structural mapping suggested that neither variant participates directly in catalysis. Growth of cultured fibroblasts from either parent was unaffected in Asn-free medium, whereas growth of the child’s cells was suppressed by about 50\\%. Analysis of Asn levels unexpectedly revealed that extracellular rather than intracellular Asn correlated with the reduced proliferation during incubation of the child’s cells in Asn-free medium. Our attempts to ectopically express the G373V variant in either HEK293T or JRS cells resulted in minimal protein production, suggesting instability. Protein expression and purification from HEK293T cells revealed reduced activity for the R519H variant relative to WT ASNS. Expression of WT ASNS in ASNS-null JRS cells resulted in nearly complete rescue of growth in Asn-free medium, whereas we observed no proliferation for the cells expressing either the G373V or R519H variant. These results support the conclusion that the coexpression of the G373V and R519H ASNS variants leads to significantly reduced Asn synthesis, which negatively impacts cellular growth. These observations are consistent with the ASNSD phenotype.},\n\tlanguage = {en},\n\tnumber = {9},\n\turldate = {2022-10-18},\n\tjournal = {Journal of Biological Chemistry},\n\tauthor = {Staklinski, Stephen J. and Chang, Mario C. and Yu, Fang and Collins Ruff, Kathleen and Franz, David N. and Qian, Zhijian and Bloom, Linda B. and Merritt, Matthew E. and McKenna, Robert and Kilberg, Michael S.},\n\tmonth = sep,\n\tyear = {2022},\n\tkeywords = {Alamut Batch 1.4.0, GATK Appistry 2013.2, Illumina HiSeq2500, NimbleGen V3, UCSC hg19, amino acid, brain metabolism, epilepsy, genetic disease, inborn error of metabolism, neurotransmitter},\n\tpages = {102385},\n}\n\n

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\n \n\n \n \n \n \n \n \n First report of a short in-frame biallelic deletion removing part of the EGF-like domain calcium-binding motif in LTBP4 and causing autosomal recessive cutis laxa type 1C.\n \n \n \n \n\n\n \n Ravel, J.; Comel, M.; Wandzel, M.; Bronner, M.; Tatopoulos, A.; Renaud, M.; Lambert, L.; Bursztejn, A.; and Bonnet, C.\n\n\n \n\n\n\n American Journal of Medical Genetics Part A, 188(11): 3343–3349. August 2022.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajmg.a.62954\n\n\n\n
\n\n\n\n \n \n $\"First$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{ravel_first_2022,\n\ttitle = {First report of a short in-frame biallelic deletion removing part of the {EGF}-like domain calcium-binding motif in {LTBP4} and causing autosomal recessive cutis laxa type {1C}},\n\tvolume = {188},\n\tissn = {1552-4833},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.62954},\n\tdoi = {10.1002/ajmg.a.62954},\n\tabstract = {Cutis laxa (CL) is a rare connective tissue disorder characterized by wrinkled, abundant and sagging skin, sometimes associated with systemic impairment. Biallelic alterations in latent transforming growth factor beta-binding protein 4 gene (LTBP4) cause autosomal recessive type 1C cutis laxa (ARCL1C, MIM \\#613177). The present report describes the case of a 17-months-old girl with cutis laxa together with a literature review of previous ARCL1C cases. Based on proband main clinical signs (cutis laxa and pulmonary emphysema), clinical exome sequencing (CES) was performed and showed a new nine base-pairs homozygous in-frame deletion in LTBP4 gene. RT-PCR and cDNA Sanger sequencing were performed in order to clarify its impact on RNA. This report demonstrates that a genetic alteration in the EGF-like 14 domain calcium-binding motif of LTBP4 gene is likely responsible for cutis laxa in our patient.},\n\tlanguage = {en},\n\tnumber = {11},\n\turldate = {2022-10-17},\n\tjournal = {American Journal of Medical Genetics Part A},\n\tauthor = {Ravel, Jean-Marie and Comel, Margot and Wandzel, Marion and Bronner, Myriam and Tatopoulos, Aurélie and Renaud, Mathilde and Lambert, Laëtitia and Bursztejn, Anne-Claire and Bonnet, Céline},\n\tmonth = aug,\n\tyear = {2022},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajmg.a.62954},\n\tkeywords = {ARCL1C, Clinical Exome Solution, DDM, LTBP4, Urban-Rifkin-Davis syndrome (URDS), autosomal recessive cutis laxa type 1C (ARCL1C), calcium-binding epidermal growth factor-like domain, clinical exome sequencing (CES)},\n\tpages = {3343--3349},\n}\n\n

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\n \n\n \n \n \n \n \n \n A deep learning approach for improved detection of homologous recombination deficiency from shallow genomic profiles.\n \n \n \n \n\n\n \n Andre, G.; Coletta, T.; Pozzorini, C.; Marques, A. C.; Bieler, J.; Kempfer, R.; Chong, C.; Saitta, A.; Smith, E.; Macheret, M.; Janiszewski, A.; Bonilla, X.; Bonet, J.; Santos-Silva, H.; Postl, M.; Wozelka-Oltjan, L.; Arrigo, N.; Willig, A.; Grimm, C.; Müllauer, L.; and Xu, Z.\n\n\n \n\n\n\n July 2022.\n Pages: 2022.07.06.498851 Section: New Results\n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@misc{andre_deep_2022,\n\ttitle = {A deep learning approach for improved detection of homologous recombination deficiency from shallow genomic profiles},\n\tcopyright = {© 2022, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution-NonCommercial-NoDerivs 4.0 International), CC BY-NC-ND 4.0, as described at http://creativecommons.org/licenses/by-nc-nd/4.0/},\n\turl = {https://www.biorxiv.org/content/10.1101/2022.07.06.498851v2},\n\tdoi = {10.1101/2022.07.06.498851},\n\tabstract = {Homologous Recombination Deficiency (HRD) is a predictive biomarker of poly-ADP ribose polymerase 1 inhibitors (PARPi) response. Most HRD detection methods are based on genome wide enumeration of scarring events and require deep genome sequence profiles ({\\textgreater} 30x). The cost and workflow-specific biases introduced by these genome profiling methods currently limits clinical adoption of HRD testing.\nWe introduce the Genomic Integrity Index (GII), a Convolutional Neuronal Network, that leverages features from low pass (1x) Whole Genome Sequencing data to distinguish HRD positive and negative samples. In a cohort of 230 ovarian and breast cancer, we found GII supports accurate stratification of samples yielding results that are highly concordant with state-of-the-art HRD detection methods (0.865{\\textless}AUC{\\textless}0.996) which require 50x deeper coverage.\nWe conclude that the deep learning framework supporting GII allows accurate detection of HRD from shallow genome profiles, reducing biases and data generation costs making it uniquely suited for clinical applications.},\n\tlanguage = {en},\n\turldate = {2022-09-28},\n\tpublisher = {bioRxiv},\n\tauthor = {Andre, Gregoire and Coletta, Tommaso and Pozzorini, Christian and Marques, Ana C. and Bieler, Jonathan and Kempfer, Rieke and Chong, Chloe and Saitta, Alexandra and Smith, Ewan and Macheret, Morgane and Janiszewski, Adrian and Bonilla, Ximena and Bonet, Jaume and Santos-Silva, Hugo and Postl, Magdalena and Wozelka-Oltjan, Lisa and Arrigo, Nils and Willig, Adrian and Grimm, Christoph and Müllauer, Leonhard and Xu, Zhenyu},\n\tmonth = jul,\n\tyear = {2022},\n\tnote = {Pages: 2022.07.06.498851\nSection: New Results},\n}\n\n

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\n \n\n \n \n \n \n \n \n P1026: COMPARATIVE GENOMIC PROFILING OF MYELOPROLIFERATIVE NEOPLASMS PRESENTING WITH AND WITHOUT SPLANCHNIC VEIN THROMBOSIS.\n \n \n \n \n\n\n \n Garrote, M.; López-Guerra, M.; Arellano-Rodrigo, E.; Magaz, M.; Triguero, A.; Carbonell, S.; Alamo, J. R.; Turon, F.; Hernandez-Gea, V.; Baiges, A.; Colomer, D.; García-Pagán, J. C.; Cervantes, F.; and Alvarez-Larrán, A.\n\n\n \n\n\n\n HemaSphere, 6: 916–917. June 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"P1026:$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 9 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{garrote_p1026_2022,\n\ttitle = {P1026: {COMPARATIVE} {GENOMIC} {PROFILING} {OF} {MYELOPROLIFERATIVE} {NEOPLASMS} {PRESENTING} {WITH} {AND} {WITHOUT} {SPLANCHNIC} {VEIN} {THROMBOSIS}},\n\tvolume = {6},\n\tissn = {2572-9241},\n\tshorttitle = {P1026},\n\turl = {https://journals.lww.com/hemasphere/Fulltext/2022/06003/P1026__COMPARATIVE_GENOMIC_PROFILING_OF.916.aspx},\n\tdoi = {10.1097/01.HS9.0000846972.47897.90},\n\tabstract = {An abstract is unavailable.},\n\tlanguage = {en-US},\n\turldate = {2022-08-22},\n\tjournal = {HemaSphere},\n\tauthor = {Garrote, M. and López-Guerra, M. and Arellano-Rodrigo, E. and Magaz, M. and Triguero, A. and Carbonell, S. and Alamo, J. R. and Turon, F. and Hernandez-Gea, V. and Baiges, A. and Colomer, D. and García-Pagán, J. C. and Cervantes, F. and Alvarez-Larrán, A.},\n\tmonth = jun,\n\tyear = {2022},\n\tkeywords = {Background:, DDM, Myeloid Solution, Myeloproliferative Neoplasms, Splanchnic vein thrombosis (SVT), myeloproliferative neoplasms (MPN)},\n\tpages = {916--917},\n}\n\n

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\n \n\n \n \n \n \n \n \n PAX2/Renal Coloboma Syndrome Expresses Extreme Intrafamilial Phenotypic Variability.\n \n \n \n \n\n\n \n Giovanella, S.; Pasini, A.; Ligabue, G.; Testa, F.; Mori, G.; Tagliafico, E.; and Magistroni, R.\n\n\n \n\n\n\n Nephron,1–7. July 2022.\n Publisher: Karger Publishers\n\n\n\n
\n\n\n\n \n \n $\"PAX2/Renal$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{giovanella_pax2renal_2022,\n\ttitle = {{PAX2}/{Renal} {Coloboma} {Syndrome} {Expresses} {Extreme} {Intrafamilial} {Phenotypic} {Variability}},\n\tissn = {1660-8151, 2235-3186},\n\turl = {https://www.karger.com/Article/FullText/525022},\n\tdoi = {10.1159/000525022},\n\tabstract = {Renal coloboma syndrome (RCS) is a disease characterized by kidney and ocular anomalies (kidney hypodysplasia and coloboma). RCS is caused, in half of the cases, by mutations in the paired box 2 (PAX2) gene, a critical organogenesis transcriptional factor. We report the case of a newborn with kidney hypodysplasia in a negative parental context where mother and father were phenotypically unaffected at the initial evaluation. The maternal family presented an important history of kidney disease with undefined diagnosis. Molecular characterization identified a PAX2 variant, classified as likely pathogenic. This variant segregates with the disease, and it was also found in the newborn, explaining his severe symptoms. It is noteworthy that the mother shows the same PAX2 variant, with an apparently negative kidney phenotype, displaying the possibility of an extreme variable expressivity of the disease. This feature suggests extreme caution in segregation analysis and family counseling of PAX2 pedigrees.},\n\tlanguage = {english},\n\turldate = {2022-08-22},\n\tjournal = {Nephron},\n\tauthor = {Giovanella, Silvia and Pasini, Andrea and Ligabue, Giulia and Testa, Francesca and Mori, Giacomo and Tagliafico, Enrico and Magistroni, Riccardo},\n\tmonth = jul,\n\tyear = {2022},\n\tpmid = {35790137},\n\tnote = {Publisher: Karger Publishers},\n\tkeywords = {DDM, NES, NES v3, PAX2, Renal coloboma syndrome (RCS)},\n\tpages = {1--7},\n}\n\n

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\n \n\n \n \n \n \n \n \n A performance evaluation study: Variant annotation tools - the enigma of clinical next generation sequencing (NGS) based genetic testing.\n \n \n \n \n\n\n \n Tuteja, S.; Kadri, S.; and Yap, K. L.\n\n\n \n\n\n\n Journal of Pathology Informatics, 13: 100130. July 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 7 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{tuteja_performance_2022,\n\ttitle = {A performance evaluation study: {Variant} annotation tools - the enigma of clinical next generation sequencing ({NGS}) based genetic testing},\n\tvolume = {13},\n\tissn = {2153-3539},\n\tshorttitle = {A performance evaluation study},\n\turl = {https://www.sciencedirect.com/science/article/pii/S2153353922007246},\n\tdoi = {10.1016/j.jpi.2022.100130},\n\tabstract = {Dramatically expanding our ability for clinical genetic testing for inherited conditions and complex diseases such as cancer, next generation sequencing (NGS) technologies are allowing for rapid interrogation of thousands of genes and identification of millions of variants. Variant annotation, the process of assigning functional information to DNA variants based on the standardized Human Genome Variation Society (HGVS) nomenclature, is a fundamental challenge in the analysis of NGS data that has led to the development of many bioinformatic algorithms. In this study, we evaluated the performance of 3 variant annotation tools: Alamut® Batch, Ensembl Variant Effect Predictor (VEP), and ANNOVAR, benchmarked by a manually curated ground-truth set of 298 variants from the medical exome database at the Molecular Diagnostics Laboratory at Lurie Children's Hospital. Of the 3 tools, VEP produces the most accurate variant annotations (HGVS nomenclature for 297 of the 298 variants) due to usage of updated gene transcript versions within the algorithm. Alamut® Batch called 296 of the 298 variants correctly; strikingly, ANNOVAR exhibited the greatest number of discrepancies (20 of the 298 variants, 93.3\\% concordance with ground-truth set). Adoption of validated methods of variant annotation is critical in post-analytical phases of clinical testing.},\n\tlanguage = {en},\n\turldate = {2022-08-22},\n\tjournal = {Journal of Pathology Informatics},\n\tauthor = {Tuteja, Sachleen and Kadri, Sabah and Yap, Kai Lee},\n\tmonth = jul,\n\tyear = {2022},\n\tkeywords = {ANNOVAR, Alamut, Alamut Batch, Gene panel, Genetic testing, Next-generation sequencing (NGS), VEP, Variant annotation},\n\tpages = {100130},\n}\n\n

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\n \n\n \n \n \n \n \n Outcomes of a multicenter study of the causes of sudden cardiac death (SCD) in the Czech Republic and primary prevention of cardiac arrest in relatives.\n \n \n \n\n\n \n Štěpánka, K. P.; Alice, K.; Pavel, V.; Petra, P.; Markéta, K.; Petra, D.; Matěj, B.; Veronika, S.; Kristina, R.; Iva, G.; Hanka, W.; Terezia, T.; Jana, H.; Markéta, S.; Andrea, G.; Veronika, Z.; Jana, P.; Martin, D.; Michal, M.; Alžběta, B.; David, V.; Hynek, Ř.; Ivan, Š.; Alexander, P.; Petr, T.; Jan, J.; Josef, K.; and Milan, M.\n\n\n \n\n\n\n Soudni Lekarstvi, 67(2): 10–24. July 2022.\n \n\n\n\n
\n\n\n\n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{stepanka_outcomes_2022,\n\ttitle = {Outcomes of a multicenter study of the causes of sudden cardiac death ({SCD}) in the {Czech} {Republic} and primary prevention of cardiac arrest in relatives},\n\tvolume = {67},\n\tissn = {0371-1854},\n\tabstract = {Sudden cardiac death (SCD) in individuals younger than 40 years has a heritable cause in a significant part of the cases. Identification of SCD, post mortem genetic analysis along with the cardiological screening examination in first degree represents an important diagnostic tool for the primary prevention of cardiac arrest in victim´s relatives and requires multicentric and multidisciplinary collaboration. Between 2016 and 2021 the complex cardiogenetic analysis was performed in 115 deaths with post mortem diagnosis of cardiomyopathy, acute aortic dissection and cases without morphological finding explaining the cause of death (sudden arrhythmic death or sudden unexplained death). DNA was isolated from post mortem collected tissue samples or relative´s blood and subjected to massively parallel sequencing (Illumina, USA) in extent of 100 to 20 000 genes. Sequencing results were analysed using the SOPHiA GENETICS DDM bioinformatics platform (Switzerland). Genetic counselling and cardiological examinations were carried out in 328 family members. Highly likely or certain molecular aetiology (i.e. based on presence of ACMG.net Class 4 to 5 variants) was disclosed in 19,8 \\% of analysed cases in RYR2, KCNH2, KCNQ1, SCN5A, FLNC (stop), GLA, TTN, TNNT2, RBM 20, MYBPC3, MYPN, FHL1, TGFBR1, and COL3A1 genes. With cardiogenetic screening we identified 25 \\% relatives at risk of life threating arrhythmias and offered them an individualised care.},\n\tlanguage = {eng},\n\tnumber = {2},\n\tjournal = {Soudni Lekarstvi},\n\tauthor = {Štěpánka, Kučerová Pohlová and Alice, Krebsová and Pavel, Votýpka and Petra, Peldová and Markéta, Kulvajtová and Petra, Dohnalová and Matěj, Bílek and Veronika, Stufka and Kristina, Rücklová and Iva, Grossová and Hanka, Wünschová and Terezia, Tavačová and Jana, Hašková and Markéta, Segeťová and Andrea, Gřegořová and Veronika, Zoubková and Jana, Petřková and Martin, Dobiáš and Michal, Makuša and Alžběta, Blanková and David, Veitr and Hynek, Řehulka and Ivan, Šubrt and Alexander, Pilin and Petr, Tomášek and Jan, Janoušek and Josef, Kautzner and Milan, Macek},\n\tmonth = jul,\n\tyear = {2022},\n\tpmid = {35882527},\n\tkeywords = {Arrhythmias, Cardiac, Czech Republic, Death, Sudden, Cardiac, Heart Arrest, Intracellular Signaling Peptides and Proteins, LIM Domain Proteins, Muscle Proteins, Primary Prevention, Sudden cardiac death, dysritmia, inherited cardiovascular diseases},\n\tpages = {10--24},\n}\n\n

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\n \n\n \n \n \n \n \n \n P690: GENE MUTATIONAL PROFILE ASSOCIATED WITH TREATMENT FAILURE OR PROGRESSION IN CHRONIC MYELOID LEUKEMIA.\n \n \n \n \n\n\n \n Estrada, N.; Xicoy, B.; Cabezón, M.; Marcé, S.; Senin, A.; Angona, A.; Alonso, E.; Ratia, M.; Plensa, M. E.; Buch, J.; Ortín, X.; and Zamora, L.\n\n\n \n\n\n\n HemaSphere, 6: 585–586. June 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"P690:$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{estrada_p690_2022,\n\ttitle = {P690: {GENE} {MUTATIONAL} {PROFILE} {ASSOCIATED} {WITH} {TREATMENT} {FAILURE} {OR} {PROGRESSION} {IN} {CHRONIC} {MYELOID} {LEUKEMIA}},\n\tvolume = {6},\n\tissn = {2572-9241},\n\tshorttitle = {P690},\n\turl = {https://journals.lww.com/hemasphere/Fulltext/2022/06003/P690__GENE_MUTATIONAL_PROFILE_ASSOCIATED_WITH.585.aspx},\n\tdoi = {10.1097/01.HS9.0000845644.95684.1e},\n\tabstract = {An abstract is unavailable.},\n\tlanguage = {en-US},\n\turldate = {2022-08-22},\n\tjournal = {HemaSphere},\n\tauthor = {Estrada, N. and Xicoy, B. and Cabezón, M. and Marcé, S. and Senin, A. and Angona, A. and Alonso, E. and Ratia, M. and Plensa, M. E. and Buch, J. and Ortín, X. and Zamora, L.},\n\tmonth = jun,\n\tyear = {2022},\n\tkeywords = {Chronic Myelomonocytic Leukemia, DDM, Myeloid Solution Capture Kit, chronic myeloid leukemia (CML), myeloid leukemia},\n\tpages = {585--586},\n}\n\n

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\n \n\n \n \n \n \n \n \n PB1918: MOLECULAR CHARACTERIZATION AND CLINICAL RELEVANCE OF ERYTHROPOIESIS IN MIELODYSPLASTIC SYNDROMES.\n \n \n \n \n\n\n \n Villalba, A.; Such, E.; Senent, L.; Mora, E.; Avetisyan, G.; Vicente, A. I.; Tormo, M.; Jerez, A.; Ramos, F.; Montoro, J.; Bernal, T.; lLuna , I.; Santiago, M.; Diaz, A.; Liquori, A.; Cervera, J.; and Sanz, G.\n\n\n \n\n\n\n HemaSphere, 6: 1797–1798. June 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"PB1918:$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{villalba_pb1918_2022,\n\ttitle = {{PB1918}: {MOLECULAR} {CHARACTERIZATION} {AND} {CLINICAL} {RELEVANCE} {OF} {ERYTHROPOIESIS} {IN} {MIELODYSPLASTIC} {SYNDROMES}.},\n\tvolume = {6},\n\tissn = {2572-9241},\n\tshorttitle = {{PB1918}},\n\turl = {https://journals.lww.com/hemasphere/Fulltext/2022/06003/PB1918__MOLECULAR_CHARACTERIZATION_AND_CLINICAL.1797.aspx},\n\tdoi = {10.1097/01.HS9.0000850524.12173.6b},\n\tabstract = {An abstract is unavailable.},\n\tlanguage = {en-US},\n\turldate = {2022-08-22},\n\tjournal = {HemaSphere},\n\tauthor = {Villalba, A. and Such, E. and Senent, L. and Mora, E. and Avetisyan, G. and Vicente, A. I. and Tormo, M. and Jerez, A. and Ramos, F. and Montoro, J. and Bernal, T. and lLuna, I. and Santiago, M. and Diaz, A. and Liquori, A. and Cervera, J. and Sanz, G.},\n\tmonth = jun,\n\tyear = {2022},\n\tkeywords = {MYS, Myelodysplastic Syndromes (MDS)},\n\tpages = {1797--1798},\n}\n\n

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\n \n\n \n \n \n \n \n \n Breast cancer in East Africa: Prevalence and spectrum of germline SNV/indel and CNVs in BRCA1 and BRCA2 genes among breast cancer patients in Tanzania.\n \n \n \n \n\n\n \n Rweyemamu, L. P.; Gültaşlar, B. K.; Akan, G.; Dharsee, N.; Namkinga, L. A.; Lyantagaye, S. L.; Yazıcı, H.; and Atalar, F.\n\n\n \n\n\n\n Cancer Medicine, n/a(n/a). July 2022.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/cam4.5091\n\n\n\n
\n\n\n\n \n \n $\"Breast$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{rweyemamu_breast_2022,\n\ttitle = {Breast cancer in {East} {Africa}: {Prevalence} and spectrum of germline {SNV}/indel and {CNVs} in {BRCA1} and {BRCA2} genes among breast cancer patients in {Tanzania}},\n\tvolume = {n/a},\n\tissn = {2045-7634},\n\tshorttitle = {Breast cancer in {East} {Africa}},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/cam4.5091},\n\tdoi = {10.1002/cam4.5091},\n\tabstract = {Background Growing prevalence and aggressiveness of breast cancer (BC) among East African women strongly indicate that the genetic risk factor implicated in the etiology of the disease may have a key role. Germline pathogenic variants in BRCA1 and BRCA2 (BRCA1/2) are known to increase the lifetime risk of BC. This study investigated the prevalence and spectrum of germline single nucleotide variant/insertion and deletion (SNV/indel), and copy number variations (CNVs) in BRCA1/2 among Tanzanian BC patients, and evaluated the associations of identified variants with patient's socio-demographic and histopathological characteristics. Methods One hundred BC patients were examined for BRCA1/2 variants using next-generation sequencing (NGS). Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) assay were performed for the confirmation of SNV/indel and CNVs, respectively. Results Six germline SNV/indel pathogenic variants were detected from six unrelated patients. Five of these variants were identified in BRCA1, and one in BRCA2. We also identified, in one patient, one variant of uncertain clinical significance (VUS). CNV was not detected in any of the BC patients. Furthermore, we found that in our cohort, BRCA1/2 variant carriers were triple-negative BC patients (p = 0.019). Conclusions Our study provides first insight into BC genetic landscape by the use of NGS in the under-represented East African Tanzanian populations. Our findings support the importance of genetic risk factors in BC etiology in Tanzania and showed a relatively high overall prevalence (6\\%) of germline BRCA1/2 pathogenic variants in BC patients. Therefore, our results indicate that BRCA1/2 pathogenic variants may well contribute to BC incidence in Tanzania. Thus, the identification of frequent variants in BRCA1/2 genes will enable implementation of rapid, inexpensive population-specific BRCA1/2 genetic testing, particularly for triple-negative BC patients known for their high prevalence in Tanzania. This will, in turn, greatly contributes to provide effective therapeutic strategies.},\n\tlanguage = {en},\n\tnumber = {n/a},\n\turldate = {2022-08-22},\n\tjournal = {Cancer Medicine},\n\tauthor = {Rweyemamu, Linus P. and Gültaşlar, Büşra K. and Akan, Gokce and Dharsee, Nazima and Namkinga, Lucy A. and Lyantagaye, Sylvester L. and Yazıcı, Hülya and Atalar, Fatmahan},\n\tmonth = jul,\n\tyear = {2022},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/cam4.5091},\n\tkeywords = {BRCA1, BRCA2, DDM, Tanzania, breast cancer, germline mutations, next-generation sequencing},\n}\n\n

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\n Background Growing prevalence and aggressiveness of breast cancer (BC) among East African women strongly indicate that the genetic risk factor implicated in the etiology of the disease may have a key role. Germline pathogenic variants in BRCA1 and BRCA2 (BRCA1/2) are known to increase the lifetime risk of BC. This study investigated the prevalence and spectrum of germline single nucleotide variant/insertion and deletion (SNV/indel), and copy number variations (CNVs) in BRCA1/2 among Tanzanian BC patients, and evaluated the associations of identified variants with patient's socio-demographic and histopathological characteristics. Methods One hundred BC patients were examined for BRCA1/2 variants using next-generation sequencing (NGS). Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) assay were performed for the confirmation of SNV/indel and CNVs, respectively. Results Six germline SNV/indel pathogenic variants were detected from six unrelated patients. Five of these variants were identified in BRCA1, and one in BRCA2. We also identified, in one patient, one variant of uncertain clinical significance (VUS). CNV was not detected in any of the BC patients. Furthermore, we found that in our cohort, BRCA1/2 variant carriers were triple-negative BC patients (p = 0.019). Conclusions Our study provides first insight into BC genetic landscape by the use of NGS in the under-represented East African Tanzanian populations. Our findings support the importance of genetic risk factors in BC etiology in Tanzania and showed a relatively high overall prevalence (6%) of germline BRCA1/2 pathogenic variants in BC patients. Therefore, our results indicate that BRCA1/2 pathogenic variants may well contribute to BC incidence in Tanzania. Thus, the identification of frequent variants in BRCA1/2 genes will enable implementation of rapid, inexpensive population-specific BRCA1/2 genetic testing, particularly for triple-negative BC patients known for their high prevalence in Tanzania. This will, in turn, greatly contributes to provide effective therapeutic strategies.\n

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\n \n\n \n \n \n \n \n \n Novel copy number variation of COLQ gene in a Moroccan patient with congenital myasthenic syndrome: a case report and review of the literature.\n \n \n \n \n\n\n \n El Kadiri, Y.; Ratbi, I.; Sefiani, A.; and Lyahyai, J.\n\n\n \n\n\n\n BMC Neurology, 22(1): 292. August 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Novel$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 7 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{el_kadiri_novel_2022,\n\ttitle = {Novel copy number variation of {COLQ} gene in a {Moroccan} patient with congenital myasthenic syndrome: a case report and review of the literature},\n\tvolume = {22},\n\tissn = {1471-2377},\n\tshorttitle = {Novel copy number variation of {COLQ} gene in a {Moroccan} patient with congenital myasthenic syndrome},\n\turl = {https://doi.org/10.1186/s12883-022-02822-y},\n\tdoi = {10.1186/s12883-022-02822-y},\n\tabstract = {Congenital myasthenic syndromes (CMSs) are rare genetic diseases due to abnormalities of the neuromuscular junction leading to permanent or transient muscle fatigability and weakness. To date, 32 genes were found to be involved in CMSs with autosomal dominant and/or recessive inheritance patterns. CMS with acetylcholinesterase deficiency, in particular, was determined to be due to biallelic mutations of COLQ gene with early-onset clinical signs. Here, we report clinical features and novel molecular findings of COLQ-related CMS in a Moroccan patient with a review of the literature for this rare form.},\n\tnumber = {1},\n\turldate = {2022-08-22},\n\tjournal = {BMC Neurology},\n\tauthor = {El Kadiri, Youssef and Ratbi, Ilham and Sefiani, Abdelaziz and Lyahyai, Jaber},\n\tmonth = aug,\n\tyear = {2022},\n\tkeywords = {COLQ gene, Case report, Clinical Exome Solution v2, Congenital myasthenic syndrome, DDM, Novel CNV, Protein-protein interaction},\n\tpages = {292},\n}\n\n

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\n \n\n \n \n \n \n \n \n Discovery and validation of dominantly inherited Alzheimer’s disease mutations in populations from Latin America.\n \n \n \n \n\n\n \n Takada, L. T.; Aláez-Verson, C.; Burgute, B. D.; Nitrini, R.; Sosa, A. L.; Castilhos, R. M.; Chaves, M. F.; Longoria, E.; Carrillo-Sánchez, K.; Brucki, S. M. D.; Flores-Lagunes, L. L.; Molina, C.; Olivares, M. J.; Ziegemeier, E.; Petranek, J.; Goate, A. M.; Cruchaga, C.; Renton, A. E.; Fernández, M. V.; Day, G. S.; McDade, E.; Bateman, R. J.; Karch, C. M.; Llibre-Guerra, J. J.; and for the Dominantly Inherited Alzheimer Network\n\n\n \n\n\n\n Alzheimer's Research & Therapy, 14(1): 108. August 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Discovery$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{takada_discovery_2022,\n\ttitle = {Discovery and validation of dominantly inherited {Alzheimer}’s disease mutations in populations from {Latin} {America}},\n\tvolume = {14},\n\tissn = {1758-9193},\n\turl = {https://doi.org/10.1186/s13195-022-01052-1},\n\tdoi = {10.1186/s13195-022-01052-1},\n\tabstract = {In fewer than 1\\% of patients, AD is caused by autosomal dominant mutations in either the presenilin 1 (PSEN1), presenilin 2 (PSEN2), or amyloid precursor protein (APP) genes. The full extent of familial AD and frequency of these variants remains understudied in Latin American (LatAm) countries. Due to the rare nature of these variants, determining the pathogenicity of a novel variant in these genes can be challenging. Here, we use a systematic approach to assign the likelihood of pathogenicity in variants from densely affected families in Latin American populations.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2022-08-22},\n\tjournal = {Alzheimer's Research \\& Therapy},\n\tauthor = {Takada, Leonel Tadao and Aláez-Verson, Carmen and Burgute, Bhagyashri D. and Nitrini, Ricardo and Sosa, Ana Luisa and Castilhos, Raphael Machado and Chaves, Marcia Fagundes and Longoria, Erika-Mariana and Carrillo-Sánchez, Karol and Brucki, Sonia Maria Dozzi and Flores-Lagunes, Luis Leonardo and Molina, Carolina and Olivares, Marcos Jimenez and Ziegemeier, Ellen and Petranek, Jennifer and Goate, Alison M. and Cruchaga, Carlos and Renton, Alan E. and Fernández, Maria Victoria and Day, Gregory S. and McDade, Eric and Bateman, Randall J. and Karch, Celeste M. and Llibre-Guerra, Jorge J. and {for the Dominantly Inherited Alzheimer Network}},\n\tmonth = aug,\n\tyear = {2022},\n\tkeywords = {Alzheimer’s disease (AD), Clinical Exome Solution v2, DDM, Dominantly inherited Alzheimer disease, Early-onset Alzheimer disease, Latin America, PSEN1, PSEN2, Presenilin 1},\n\tpages = {108},\n}\n\n

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\n \n\n \n \n \n \n \n \n Genomic surveillance of SARS-CoV-2 in patients presenting neurological manifestations.\n \n \n \n \n\n\n \n Vicco, A.; Caccuri, F.; Messali, S.; Vitiello, A.; Emmi, A.; Vecchio, C. D.; Reale, A.; Caruso, A.; Ottaviano, G.; Mucignat, C.; Parolin, C.; Antonini, A.; and Calistri, A.\n\n\n \n\n\n\n PLOS ONE, 17(6): e0270024. June 2022.\n Publisher: Public Library of Science\n\n\n\n
\n\n\n\n \n \n $\"Genomic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{vicco_genomic_2022,\n\ttitle = {Genomic surveillance of {SARS}-{CoV}-2 in patients presenting neurological manifestations},\n\tvolume = {17},\n\tissn = {1932-6203},\n\turl = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0270024},\n\tdoi = {10.1371/journal.pone.0270024},\n\tabstract = {During the first wave of infections, neurological symptoms in Coronavirus Disease 2019 (COVID-19) patients raised particular concern, suggesting that, in a subset of patients, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could invade and damage cells of the central nervous system (CNS). Indeed, up to date several in vitro and in vivo studies have shown the ability of SARS-CoV-2 to reach the CNS. Both viral and/or host related features could explain why this occurs only in certain individuals and not in all the infected population. The aim of the present study was to evaluate if onset of neurological manifestations in COVID-19 patients was related to specific viral genomic signatures. To this end, viral genome was extracted directly from nasopharyngeal swabs of selected SARS-CoV-2 positive patients presenting a spectrum of neurological symptoms related to COVID-19, ranging from anosmia/ageusia to more severe symptoms. By adopting a whole genome sequences approach, here we describe a panel of known as well as unknown mutations detected in the analyzed SARS-CoV-2 genomes. While some of the found mutations were already associated with an improved viral fitness, no common signatures were detected when comparing viral sequences belonging to specific groups of patients. In conclusion, our data support the notion that COVID-19 neurological manifestations are mainly linked to patient-specific features more than to virus genomic peculiarities.},\n\tlanguage = {en},\n\tnumber = {6},\n\turldate = {2022-07-28},\n\tjournal = {PLOS ONE},\n\tauthor = {Vicco, Anna and Caccuri, Francesca and Messali, Serena and Vitiello, Adriana and Emmi, Aron and Vecchio, Claudia Del and Reale, Alberto and Caruso, Arnaldo and Ottaviano, Giancarlo and Mucignat, Carla and Parolin, Cristina and Antonini, Angelo and Calistri, Arianna},\n\tmonth = jun,\n\tyear = {2022},\n\tnote = {Publisher: Public Library of Science},\n\tkeywords = {COVID 19, Genomics, Microbial mutation, Mutation databases, SARS-CoV-2, SOPHiA DDM, Substitution mutation, Viral genome, Viral genomics},\n\tpages = {e0270024},\n}\n\n

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\n \n\n \n \n \n \n \n Hedgehog Signal Defect Leading to Familial Exudative Vitreoretinopathy-Like Disease and Gastrointestinal Malformation.\n \n \n \n\n\n \n Şahinoğlu Keşkek, N.; Akkoyun, İ.; Temiz, A.; and Kütük, Ö.\n\n\n \n\n\n\n Turkish Journal of Ophthalmology, 52(3): 174–178. June 2022.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{sahinoglu_keskek_hedgehog_2022,\n\ttitle = {Hedgehog {Signal} {Defect} {Leading} to {Familial} {Exudative} {Vitreoretinopathy}-{Like} {Disease} and {Gastrointestinal} {Malformation}},\n\tvolume = {52},\n\tissn = {2149-8709},\n\tdoi = {10.4274/tjo.galenos.2021.72929},\n\tabstract = {Objectives: The aim of the study was to present a new genetic association presenting with gastrointestinal tract malformations (GTMs) and familial exudative vitreoretinopathy (FEVR)-like disease and review the genetics of Hedgehog signaling.\nMaterials and Methods: Three neonates were diagnosed with FEVR-like retinal vascular disease upon routine ophthalmological examination during hospitalization in the neonatal surgical intensive care unit for GTMs. Genetic analysis of the neonates was performed.\nResults: Gestational age of the neonates was 39, 38, and 39 weeks and birth weights were 3,500, 3,600, and 3,300 grams, respectively. All six eyes of the three infants were treated by laser photocoagulation. Recurrence was not seen in any of the eyes. Genetical analysis of all the neonates diagnosed with FEVR-like disease revealed defects in the Hedgehog pathway.\nConclusion: FEVR is a genetically well-defined retinal vascular disease. The current study is the first to show an association between FEVR-like retinal vascular disease and GTMs. This study demonstrates the importance of the Hedgehog pathway in retinal vascular and gut development.},\n\tlanguage = {eng},\n\tnumber = {3},\n\tjournal = {Turkish Journal of Ophthalmology},\n\tauthor = {Şahinoğlu Keşkek, Nedime and Akkoyun, İmren and Temiz, Abdülkerim and Kütük, Özgür},\n\tmonth = jun,\n\tyear = {2022},\n\tpmid = {35770050},\n\tpmcid = {PMC9249105},\n\tkeywords = {Eye Diseases, FEVR, Familial Exudative Vitreoretinopathies, Hedgehog Proteins, Infant, Newborn, Retinal Diseases, SOPHiA DDM, Vascular Diseases, WES, gastrointestinal tract malformations, retinal vasculardisease},\n\tpages = {174--178},\n}\n\n

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\n \n\n \n \n \n \n \n \n Next-Generation Sequencing Advances the Genetic Diagnosis of Cerebral Cavernous Malformation (CCM).\n \n \n \n \n\n\n \n Benedetti, V.; Canzoneri, R.; Perrelli, A.; Arduino, C.; Zonta, A.; Brusco, A.; and Retta, S. F.\n\n\n \n\n\n\n Antioxidants, 11(7): 1294. June 2022.\n Number: 7 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Next-Generation$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{benedetti_next-generation_2022,\n\ttitle = {Next-{Generation} {Sequencing} {Advances} the {Genetic} {Diagnosis} of {Cerebral} {Cavernous} {Malformation} ({CCM})},\n\tvolume = {11},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2076-3921},\n\turl = {https://www.mdpi.com/2076-3921/11/7/1294},\n\tdoi = {10.3390/antiox11071294},\n\tabstract = {Cerebral Cavernous Malformation (CCM) is a cerebrovascular disease of genetic origin that predisposes to seizures, focal neurological deficits and fatal intracerebral hemorrhage. It may occur sporadically or in familial forms, segregating as an autosomal dominant condition with incomplete penetrance and highly variable expressivity. Its pathogenesis has been associated with loss-of-function mutations in three genes, namely KRIT1 (CCM1), CCM2 and PDCD10 (CCM3), which are implicated in defense mechanisms against oxidative stress and inflammation. Herein, we screened 21 Italian CCM cases using clinical exome sequencing and found six cases ({\\textasciitilde}29\\%) with pathogenic variants in CCM genes, including a large 145–256 kb genomic deletion spanning the KRIT1 gene and flanking regions, and the KRIT1 c.1664C{\\textgreater}T variant, which we demonstrated to activate a donor splice site in exon 16. The segregation of this cryptic splicing mutation was studied in a large Italian family (five affected and seven unaffected cases), and showed a largely heterogeneous clinical presentation, suggesting the implication of genetic modifiers. Moreover, by analyzing ad hoc gene panels, including a virtual panel of 23 cerebrovascular disease-related genes (Cerebro panel), we found two variants in NOTCH3 and PTEN genes, which could contribute to the abnormal oxidative stress and inflammatory responses to date implicated in CCM disease pathogenesis.},\n\tlanguage = {en},\n\tnumber = {7},\n\turldate = {2022-07-28},\n\tjournal = {Antioxidants},\n\tauthor = {Benedetti, Valerio and Canzoneri, Rosalia and Perrelli, Andrea and Arduino, Carlo and Zonta, Andrea and Brusco, Alfredo and Retta, Saverio Francesco},\n\tmonth = jun,\n\tyear = {2022},\n\tnote = {Number: 7\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {CES, NGS, SOPHiA DDM, cerebral cavernous malformation (CCM), cerebrovascular disease},\n\tpages = {1294},\n}\n\n

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\n \n\n \n \n \n \n \n Pathogenicity Reclassification of Genetic Variants Related to Early-Onset Breast Cancer among Women of Mongoloid Origin.\n \n \n \n\n\n \n Gervas, P.; Molokov, A.; Babyshkina, N.; Kiselev, A.; Zarubin, A.; Yumov, E.; Pisareva, L.; Choynzonov, E.; and Cherdyntseva, N.\n\n\n \n\n\n\n Asian Pacific journal of cancer prevention: APJCP, 23(6): 2027–2033. June 2022.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{gervas_pathogenicity_2022,\n\ttitle = {Pathogenicity {Reclassification} of {Genetic} {Variants} {Related} to {Early}-{Onset} {Breast} {Cancer} among {Women} of {Mongoloid} {Origin}},\n\tvolume = {23},\n\tissn = {2476-762X},\n\tdoi = {10.31557/APJCP.2022.23.6.2027},\n\tabstract = {BACKGROUND: Germline alterations in BRCA1, BRCA2, and other genes are responsible for early-onset breast cancer. However, up to 20\\% of molecular tests report genetic variant of unknown significance (VUS) or novel variants that have never been previously described and their clinical significance are unknown. This study aimed to reclassify variant of unknown significance (VUS) or novel variants by using the ActiveDriveDB database that annotates variants through the lens of sites of post-translational modifications (PTM).\nMETHODS: Our study included thirty-eighth young Buryat BC patients, belonging to the Mongoloid race and anthropologically to the Central Asia. Genomic DNA was extracted from the peripheral blood lymphocytes using the phenol/chloroform method. DNA library were prepared using the Hereditary Cancer SolutionTM kit (Sophia GENETICS, Switzerland) to cover 27 genes, such as ATM, APC, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, FAM175A, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PALB2, PIK3CA, PMS2, PMS2CL, PTEN, RAD50, RAD51C, RAD51D, STK11, TP53, and XRCC2. Paired-end sequencing (2 x 150 bp) was conducted using NextSeq 500 system (Illumina, USA).\nRESULTS: We re-examined 135 rare variants (41 VUS, 25 conflicting, 64 benign and 5 new variants). We identified 10 out of 135 (7.4\\%) mutations that affected the sites of post-translational modification in proteins. Of 135 rare mutations, 1 benign variant was reclassified as network-rewiring - motif loss mutation, 3 VUS and 1 new variant were reclassified as distal PTM- mutations, 2 new and 1 benign variant were classified as proximal PTM- mutations and 1 benign and 1 conflicting variant were classified as direct PTM- mutations.\nCONCLUSIONS: For the first time, 7.4\\% (10 out of 135) of mutations that affected the sites of post-translational modification in proteins were identified among early-onset breast cancer women of Mongoloid origin.},\n\tlanguage = {eng},\n\tnumber = {6},\n\tjournal = {Asian Pacific journal of cancer prevention: APJCP},\n\tauthor = {Gervas, Polina and Molokov, Aleksey and Babyshkina, Nataliya and Kiselev, Artem and Zarubin, Aleksei and Yumov, Evgeny and Pisareva, Lubov and Choynzonov, Evgeny and Cherdyntseva, Nadezda},\n\tmonth = jun,\n\tyear = {2022},\n\tpmid = {35763645},\n\tkeywords = {Breast Neoplasms, Central Asia, DNA-Binding Proteins, Genes, BRCA2, HCS, High-Throughput Nucleotide Sequencing, Mongoloid race, VUS, Virulence, breast cancer},\n\tpages = {2027--2033},\n}\n\n

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\n \n\n \n \n \n \n \n \n Optimizing treatment selection and sequencing decisions for first-line maintenance therapy of newly diagnosed advanced ovarian cancer – International considerations amongst upper middle- and high-income countries (UMIC and HIC).\n \n \n \n \n\n\n \n Goh, J. C. H.; Gourley, C.; Tan, D. S P; Nogueira-Rodrigues, A.; Elghazaly, H.; Edy Pierre, M.; Giornelli, G.; Kim, B.; Morales–Vasquez, F.; and Tyulyandina, A.\n\n\n \n\n\n\n Gynecologic Oncology Reports, 42: 101028. June 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Optimizing$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{goh_optimizing_2022,\n\ttitle = {Optimizing treatment selection and sequencing decisions for first-line maintenance therapy of newly diagnosed advanced ovarian cancer – {International} considerations amongst upper middle- and high-income countries ({UMIC} and {HIC})},\n\tvolume = {42},\n\tissn = {2352-5789},\n\turl = {https://www.sciencedirect.com/science/article/pii/S2352578922001084},\n\tdoi = {10.1016/j.gore.2022.101028},\n\tabstract = {The incidence and mortality rates of ovarian cancer are increasing globally. Ovarian cancer is diagnosed at an advanced stage in 80\\% of women. After standard, platinum-based, front-line chemotherapy, poly (ADP-ribose) polymerase (PARP) inhibitors and antiangiogenic agents are successfully employed as maintenance strategies for newly diagnosed, advanced ovarian cancer patients. Landmark clinical studies, including SOLO-1, PAOLA-1, PRIMA, and VELIA, have provided crucial insights on optimizing first-line maintenance treatment using PARP inhibitors. A group of ovarian cancer experts, (primarily from upper middle \\& high income countries outside US, China, Japan \\& Europe) met in September 2019 to discuss new developments for the first-line treatment of ovarian cancer and its implications. Key implications of the evolving clinical data included: (1) olaparib or niraparib maintenance therapy appears to be the preferred choice for patients with BRCA1/2 mutations; hence, BRCA testing is beneficial in identifying these patients; (2) niraparib monotherapy and olaparib in combination with bevacizumab have demonstrated significant benefit in progression-free survival (PFS) in homologous recombination deficiency (HRD)-positive patients; (3) bevacizumab, niraparib alone, or observation can be an alternative for HRD-negative patients; (4) further data is warranted to explore the role of PARP inhibitors in treating HRD-negative, ovarian cancer patients to confirm findings of the exploratory analysis of PRIMA; (5) PARP inhibitors may be beneficial for stage IV ovarian cancer patients with inoperable disease and patients with prior neoadjuvant chemotherapy; and (6) there is an urgent need to increase awareness in both clinicians and patients on BRCA and HRD testing for optimizing treatment decision-making and improving clinical outcomes in newly diagnosed, advanced ovarian cancer patients. In clinical medicine, the limited availability of family history (FH) information and the complexity of FH criteriahas hampered the implementation of BRCA testing. Moreover, many cancer patients with BRCA mutations are not tested because they do not meet the criteria for FH. Consequently, BRCA testing in many high income countries, including the US and Australia, is underused and used inappropriately, which has resulted in the loss of valuable opportunities for better cancer management and cancer prevention.},\n\tlanguage = {en},\n\turldate = {2022-07-28},\n\tjournal = {Gynecologic Oncology Reports},\n\tauthor = {Goh, Jeffrey C. H. and Gourley, Charlie and Tan, David S P and Nogueira-Rodrigues, Angélica and Elghazaly, Hesham and Edy Pierre, Marc and Giornelli, Gonzalo and Kim, Byoung-Gie and Morales–Vasquez, Flavia and Tyulyandina, Alexandra},\n\tmonth = jun,\n\tyear = {2022},\n\tkeywords = {BRCA1/2, HRD, HRR, PARP inhibitors},\n\tpages = {101028},\n}\n\n

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\n The incidence and mortality rates of ovarian cancer are increasing globally. Ovarian cancer is diagnosed at an advanced stage in 80% of women. After standard, platinum-based, front-line chemotherapy, poly (ADP-ribose) polymerase (PARP) inhibitors and antiangiogenic agents are successfully employed as maintenance strategies for newly diagnosed, advanced ovarian cancer patients. Landmark clinical studies, including SOLO-1, PAOLA-1, PRIMA, and VELIA, have provided crucial insights on optimizing first-line maintenance treatment using PARP inhibitors. A group of ovarian cancer experts, (primarily from upper middle & high income countries outside US, China, Japan & Europe) met in September 2019 to discuss new developments for the first-line treatment of ovarian cancer and its implications. Key implications of the evolving clinical data included: (1) olaparib or niraparib maintenance therapy appears to be the preferred choice for patients with BRCA1/2 mutations; hence, BRCA testing is beneficial in identifying these patients; (2) niraparib monotherapy and olaparib in combination with bevacizumab have demonstrated significant benefit in progression-free survival (PFS) in homologous recombination deficiency (HRD)-positive patients; (3) bevacizumab, niraparib alone, or observation can be an alternative for HRD-negative patients; (4) further data is warranted to explore the role of PARP inhibitors in treating HRD-negative, ovarian cancer patients to confirm findings of the exploratory analysis of PRIMA; (5) PARP inhibitors may be beneficial for stage IV ovarian cancer patients with inoperable disease and patients with prior neoadjuvant chemotherapy; and (6) there is an urgent need to increase awareness in both clinicians and patients on BRCA and HRD testing for optimizing treatment decision-making and improving clinical outcomes in newly diagnosed, advanced ovarian cancer patients. In clinical medicine, the limited availability of family history (FH) information and the complexity of FH criteriahas hampered the implementation of BRCA testing. Moreover, many cancer patients with BRCA mutations are not tested because they do not meet the criteria for FH. Consequently, BRCA testing in many high income countries, including the US and Australia, is underused and used inappropriately, which has resulted in the loss of valuable opportunities for better cancer management and cancer prevention.\n

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\n \n\n \n \n \n \n \n \n Validation of AmpliSeq NGS Panel for BRCA1 and BRCA2 Variant Detection in Canine Formalin-Fixed Paraffin-Embedded Mammary Tumors.\n \n \n \n \n\n\n \n Di Giacomo, D.; Di Domenico, M.; Defourny, S. V. P.; Malatesta, D.; Di Teodoro, G.; Martino, M.; Viola, A.; D’Alterio, N.; Cammà, C.; Modesto, P.; and Petrini, A.\n\n\n \n\n\n\n Life, 12(6): 851. June 2022.\n Number: 6 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Validation$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{di_giacomo_validation_2022,\n\ttitle = {Validation of {AmpliSeq} {NGS} {Panel} for {BRCA1} and {BRCA2} {Variant} {Detection} in {Canine} {Formalin}-{Fixed} {Paraffin}-{Embedded} {Mammary} {Tumors}},\n\tvolume = {12},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2075-1729},\n\turl = {https://www.mdpi.com/2075-1729/12/6/851},\n\tdoi = {10.3390/life12060851},\n\tabstract = {Mammary carcinomas are the most common neoplasms observed in women and in female dogs. Canine mammary tumors show epidemiological, clinical, genetic, and prognostic characteristics comparable to human breast cancers. The recent introduction of next generation sequencing (NGS) technologies has greatly improved research and diagnostics for humans, while these new tools still need to be implemented in animal models. In this study we developed and validated an AmpliSeq Panel assay for the identification of BRCA variants in twenty-two different dogs. The amplicon mean coverage was 5499× and uniformity was higher than 98\\% in all samples. The results of germline single nucleotide variants (SNVs) and insertions/deletions (INDELs) were fully concordant regardless of the types of samples considered (blood, fresh and FFPE tissues). Moreover, despite the high DNA degradation observed in older FFPE blocks ({\\textgreater}5 years), the assay allowed full coverage of all amplicons for downstream analyses. We consider the NGS panel developed in this study as a useful tool for expanding information on BRCA genes in the veterinary field and for human health from a comparative oncology perspective.},\n\tlanguage = {en},\n\tnumber = {6},\n\turldate = {2022-07-28},\n\tjournal = {Life},\n\tauthor = {Di Giacomo, Daniela and Di Domenico, Marco and Defourny, Sabrina Vanessa Patrizia and Malatesta, Daniela and Di Teodoro, Giovanni and Martino, Michele and Viola, Antonello and D’Alterio, Nicola and Cammà, Cesare and Modesto, Paola and Petrini, Antonio},\n\tmonth = jun,\n\tyear = {2022},\n\tnote = {Number: 6\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Alamut, BRCA1, BRCA2, FFPE, INDEL, NGS, SNV},\n\tpages = {851},\n}\n\n

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\n \n\n \n \n \n \n \n \n Seven pediatric Cases with Familial hypomagnesemia with hypercalciuria and nephrocalcinosis.\n \n \n \n \n\n\n \n \n\n\n \n\n\n\n June 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Seven$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 8 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@misc{noauthor_seven_2022,\n\ttitle = {Seven pediatric {Cases} with {Familial} hypomagnesemia with hypercalciuria and nephrocalcinosis},\n\turl = {https://www.researchsquare.com},\n\tabstract = {Purpose: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal-recessive renal tubular disorder. FHHNC is characterized by renal wasting of magnesium (Mg) and calcium (Ca), which subsequently leads to bilateral nephrocalcinosis, renal sto...},\n\tlanguage = {en},\n\turldate = {2022-07-28},\n\tmonth = jun,\n\tyear = {2022},\n\tdoi = {10.21203/rs.3.rs-1719871/v1},\n\tkeywords = {CES, SOPHiA DDM, WES},\n}\n\n

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\n \n\n \n \n \n \n \n \n Generation of the induced pluripotent stem cell line UNIBSi017-A from an individual with cardiospondylocarpofacial syndrome and the MAP3K7 c.737-7A \\textgreater G variant.\n \n \n \n \n\n\n \n Calamaio, S.; Serzanti, M.; Morlino, S.; Massardi, M.; Ritelli, M.; Piovani, G.; Colombi, M.; Cortellini, V.; Castori, M.; Dell'Era, P.; and Micale, L.\n\n\n \n\n\n\n Stem Cell Research, 63: 102837. June 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Generation$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 7 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{calamaio_generation_2022,\n\ttitle = {Generation of the induced pluripotent stem cell line {UNIBSi017}-{A} from an individual with cardiospondylocarpofacial syndrome and the {MAP3K7} c.737-{7A} {\\textgreater} {G} variant},\n\tvolume = {63},\n\tissn = {1873-5061},\n\turl = {https://www.sciencedirect.com/science/article/pii/S1873506122001866},\n\tdoi = {10.1016/j.scr.2022.102837},\n\tabstract = {TAK1 is a serine threonine kinase that mediates signal transduction induced by TGFβ and bone morphogenetic proteins, and controls a variety of cell functions by modulating the downstream activation of NF-kkB, JNK, and p38. Heterozygous variants in the coding MAP3K7 gene cause the cardiospondylocarpofacial syndrome, characterized by various abnormalities. Skin fibroblasts derived from a patient carrying the MAP3K7 c.737-7A{\\textgreater}G heterozygous variant were reprogrammed using Sendai viral vector system carrying the Yamanaka factors. The generated induced pluripotent stem cells (iPSC) line retained the original genotype, expressed pluripotency markers, and differentiated into cells of the three germ layers.},\n\tlanguage = {en},\n\turldate = {2022-07-28},\n\tjournal = {Stem Cell Research},\n\tauthor = {Calamaio, Serena and Serzanti, Marialaura and Morlino, Silvia and Massardi, Marialuisa and Ritelli, Marco and Piovani, Giovanna and Colombi, Marina and Cortellini, Venusia and Castori, Marco and Dell'Era, Patrizia and Micale, Lucia},\n\tmonth = jun,\n\tyear = {2022},\n\tkeywords = {Alamut, MAP3K7},\n\tpages = {102837},\n}\n\n

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\n \n\n \n \n \n \n \n \n Proper Selection of In Vitro Cell Model Affects the Characterization of the Neutralizing Antibody Response against SARS-CoV-2.\n \n \n \n \n\n\n \n Criscuolo, E.; Giuliani, B.; Ferrari, D.; Ferrarese, R.; Diotti, R. A.; Clementi, M.; Mancini, N.; and Clementi, N.\n\n\n \n\n\n\n Viruses, 14(6): 1232. June 2022.\n Number: 6 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Proper$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{criscuolo_proper_2022,\n\ttitle = {Proper {Selection} of {In} {Vitro} {Cell} {Model} {Affects} the {Characterization} of the {Neutralizing} {Antibody} {Response} against {SARS}-{CoV}-2},\n\tvolume = {14},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {1999-4915},\n\turl = {https://www.mdpi.com/1999-4915/14/6/1232},\n\tdoi = {10.3390/v14061232},\n\tabstract = {(1) Background: Our aim is the evaluation of the neutralizing activity of BNT162b2 mRNA vaccine-induced antibodies in different in vitro cellular models, as this still represents one of the surrogates of protection against SARS-CoV-2 viral variants. (2) Methods: The entry mechanisms of SARS-CoV-2 in three cell lines (Vero E6, Vero E6/TMPRSS2 and Calu-3) were evaluated with both pseudoviruses and whole virus particles. The neutralizing capability of sera collected from vaccinated subjects was characterized through cytopathic effects and Real-Time RT PCR. (3) Results: In contrast to Vero E6 and Vero E6/TMPRSS2, Calu-3 allowed the evaluation of both viral entry mechanisms, resembling what occurs during natural infection. The choice of an appropriate cellular model can decisively influence the determination of the neutralizing activity of antibodies against SARS-CoV-2 variants. Indeed, the lack of correlation between neutralizing data in Calu-3 and Vero E6 demonstrated that testing the antibody inhibitory activity by using a single cell model possibly results in an inaccurate characterization. (4) Conclusions: Cellular systems allowing only one of the two viral entry pathways may not fully reflect the neutralizing activity of vaccine-induced antibodies moving increasingly further away from possible correlates of protection from SARS-CoV-2 infection.},\n\tlanguage = {en},\n\tnumber = {6},\n\turldate = {2022-07-28},\n\tjournal = {Viruses},\n\tauthor = {Criscuolo, Elena and Giuliani, Benedetta and Ferrari, Davide and Ferrarese, Roberto and Diotti, Roberta A. and Clementi, Massimo and Mancini, Nicasio and Clementi, Nicola},\n\tmonth = jun,\n\tyear = {2022},\n\tnote = {Number: 6\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {BNT162b2 mRNA vaccine, COVID-19 vaccine, SARS-CoV-2, SOPHiA DDM, VOCs, antibody response, neutralizing activity},\n\tpages = {1232},\n}\n\n

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\n \n\n \n \n \n \n \n \n Retrotransposon insertion as a novel mutational cause of spinal muscular atrophy.\n \n \n \n \n\n\n \n \n\n\n \n\n\n\n June 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Retrotransposon$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@misc{noauthor_retrotransposon_2022,\n\ttitle = {Retrotransposon insertion as a novel mutational cause of spinal muscular atrophy},\n\turl = {https://www.researchsquare.com},\n\tabstract = {Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder resulting from biallelic alterations of the SMN1 gene: deletion, gene conversion or, in rare cases, intragenic variants. The disease severity is mainly influenced by the copy number of SMN2, a near...},\n\tlanguage = {en},\n\turldate = {2022-07-28},\n\tmonth = jun,\n\tyear = {2022},\n\tdoi = {10.21203/rs.3.rs-1666246/v1},\n\tkeywords = {Alamut, SMN1, SMN2},\n}\n\n

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\n \n\n \n \n \n \n \n \n A deep learning solution for detection of homologous recombination deficiency in ovarian cancer using low pass whole-genome sequencing: Evaluation of the analytical performance.\n \n \n \n \n\n\n \n Buisson, A.; Saintigny, P.; Pujade-Lauraine, E.; Montoto-Grillot, C.; Vacirca, D.; Barberis, M.; Colombo, N.; Harle, A.; Gilson, P.; Roma, C.; Bergantino, F.; Harter, P.; Pignata, S.; Gonzalez Martin, A.; Schauer, C.; Fujiwara, K.; Vergote, I.; Nøttrup, T. J.; Just, P.; and Ray-Coquard, I. L.\n\n\n \n\n\n\n Journal of Clinical Oncology, 40(16_suppl): e17599–e17599. June 2022.\n Publisher: Wolters Kluwer\n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{buisson_deep_2022,\n\ttitle = {A deep learning solution for detection of homologous recombination deficiency in ovarian cancer using low pass whole-genome sequencing: {Evaluation} of the analytical performance.},\n\tvolume = {40},\n\tissn = {0732-183X},\n\tshorttitle = {A deep learning solution for detection of homologous recombination deficiency in ovarian cancer using low pass whole-genome sequencing},\n\turl = {https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.e17599},\n\tdoi = {10.1200/JCO.2022.40.16_suppl.e17599},\n\tabstract = {e17599\n\nBackground: Poly (ADP-ribose) polymerase inhibitors (PARPi) induce synthetic lethality in cells with homologous recombination deficiency (HRD). PARPi treatment revolutionized management of patients with cancer, particularly in types where HRD is common, such as ovarian and breast cancer. However, challenges in the implementation of available methods currently limit adoption of HRD testing in the clinics. Here we present the analytical performance evaluation of the Genomic Integrity Index (GII) (SOPHiA GENETICs SA). Methods: GII is a deep-learning based solution for identification of HRD positive tumors from low-pass whole genome sequencing (lpWGS) data (X1 fold coverage). The analytical performance of the GII was evaluated as positive (PPA), negative (NPA) and overall (OPA) percentage of agreement with the HRD status determined by Myriad myChoice CDx (Myriad Genetic Laboratories, Inc.; US FDA-approved). We generated whole genome sequencing libraries for DNA extracted from 139 ovarian cancer Formalin-Fixed Paraffin- Embedded samples, in 4 independent clinical laboratories. We sequenced to the equivalent of 1X coverage (̃10 million reads, 150 base paired end reads, Illumina) and performed HRD classification data using GII using manufacturer’s recommended thresholds. Results: The GII demonstrated high analytical concordance with Myriad myChoice CDx with 91.7\\% PPA, 95.5\\% NPA and 94.5\\% OPA (Table). The HRD status obtained by GII from a subset of positive and negative samples was 100\\% reproducible (n = 4) between runs. Conclusions: The HRD status obtained by GII is highly concordant with that obtained from standard method, supporting that GII allows accurate and reproducible detection of HRD from lpWGS data. LpWGS is amongst the most cost-effective and easy to implement genome profiling methods, making it uniquely suited for clinical applications.\n\nConfusion matrix of comparison between Myriad myChoice CDx and GII results.\n\n\n\tSOPHiA GENETICS GII status\n\nPositive\n\tNegative\n\nMyriad myChoice\n\nCDx status\n\tPositive\n\t66\n\t6\n\nNegative\n\t3\n\t64},\n\tnumber = {16\\_suppl},\n\turldate = {2022-07-28},\n\tjournal = {Journal of Clinical Oncology},\n\tauthor = {Buisson, Adrien and Saintigny, Pierre and Pujade-Lauraine, Eric and Montoto-Grillot, Christine and Vacirca, Davide and Barberis, Massimo and Colombo, Nicoletta and Harle, Alexandre and Gilson, Pauline and Roma, Cristin and Bergantino, Francesca and Harter, Philipp and Pignata, Sandro and Gonzalez Martin, Antonio and Schauer, Christian and Fujiwara, Keiichi and Vergote, Ignace and Nøttrup, Trine Jakobi and Just, Pierre-Alexandre and Ray-Coquard, Isabelle Laure},\n\tmonth = jun,\n\tyear = {2022},\n\tnote = {Publisher: Wolters Kluwer},\n\tkeywords = {GII, Genomic Integrity Index, HRD},\n\tpages = {e17599--e17599},\n}\n\n

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\n e17599 Background: Poly (ADP-ribose) polymerase inhibitors (PARPi) induce synthetic lethality in cells with homologous recombination deficiency (HRD). PARPi treatment revolutionized management of patients with cancer, particularly in types where HRD is common, such as ovarian and breast cancer. However, challenges in the implementation of available methods currently limit adoption of HRD testing in the clinics. Here we present the analytical performance evaluation of the Genomic Integrity Index (GII) (SOPHiA GENETICs SA). Methods: GII is a deep-learning based solution for identification of HRD positive tumors from low-pass whole genome sequencing (lpWGS) data (X1 fold coverage). The analytical performance of the GII was evaluated as positive (PPA), negative (NPA) and overall (OPA) percentage of agreement with the HRD status determined by Myriad myChoice CDx (Myriad Genetic Laboratories, Inc.; US FDA-approved). We generated whole genome sequencing libraries for DNA extracted from 139 ovarian cancer Formalin-Fixed Paraffin- Embedded samples, in 4 independent clinical laboratories. We sequenced to the equivalent of 1X coverage (̃10 million reads, 150 base paired end reads, Illumina) and performed HRD classification data using GII using manufacturer’s recommended thresholds. Results: The GII demonstrated high analytical concordance with Myriad myChoice CDx with 91.7% PPA, 95.5% NPA and 94.5% OPA (Table). The HRD status obtained by GII from a subset of positive and negative samples was 100% reproducible (n = 4) between runs. Conclusions: The HRD status obtained by GII is highly concordant with that obtained from standard method, supporting that GII allows accurate and reproducible detection of HRD from lpWGS data. LpWGS is amongst the most cost-effective and easy to implement genome profiling methods, making it uniquely suited for clinical applications. Confusion matrix of comparison between Myriad myChoice CDx and GII results. SOPHiA GENETICS GII status Positive Negative Myriad myChoice CDx status Positive 66 6 Negative 3 64\n

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\n \n\n \n \n \n \n \n \n Competition for Dominance Within Replicating Quasispecies During Prolonged SARS-CoV-2 Infection in an Immunocompromised Host.\n \n \n \n \n\n\n \n Caccuri, F.; Messali, S.; Bortolotti, D.; Di Silvestre, D.; De Palma, A.; Cattaneo, C.; Bertelli, A.; Zani, A.; Milanesi, M.; Giovanetti, M.; Campisi, G.; Gentili, V.; Bugatti, A.; Filippini, F.; Scaltriti, E.; Pongolini, S.; Tucci, A.; Fiorentini, S.; d’Ursi , P.; Ciccozzi, M.; Mauri, P.; Rizzo, R.; and Caruso, A.\n\n\n \n\n\n\n Virus Evolution,veac042. May 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Competition$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{caccuri_competition_2022,\n\ttitle = {Competition for {Dominance} {Within} {Replicating} {Quasispecies} {During} {Prolonged} {SARS}-{CoV}-2 {Infection} in an {Immunocompromised} {Host}},\n\tissn = {2057-1577},\n\turl = {https://doi.org/10.1093/ve/veac042},\n\tdoi = {10.1093/ve/veac042},\n\tabstract = {SARS-CoV-2 variants of concern (VOCs) emerge for their capability to better adapt to the human host aimed and enhance human-to-human transmission. Mutations in spike largely contributed to adaptation. Viral persistence is a prerequisite for intra-host virus evolution, and this likely occurred in immunocompromised patients who allow intra-host long-term viral replication. The underlying mechanism leading to the emergence of variants during viral persistence in the immunocompromised host is still unknown. Here we show the existence of an ensemble of minor mutants in the early biological samples obtained from an immunocompromised patient and their dynamic interplay with the master mutant during a persistent and productive long-term infection. In particular, after 222 days of active viral replication the original master mutant, named MB61°, was replaced by a minor quasispecies (MB61222) expressing two critical mutations in spike, namely Q493K and N501T. Isolation of the two viruses allowed us to show that MB61222 entry into target cells occurred mainly by the fusion at the plasma membrane (PM), whereas endocytosis characterized the entry mechanism used by MB61°. Interestingly, co-infection of two human cell lines of different origin with the SARS-CoV-2 isolates highlighted the early and dramatic predominance of MB61222 over MB61° replication. This finding may be explained by a faster replicative activity of MB61222 as compared to MB61° as well as by the capability of MB61222 to induce peculiar viral RNA sensing mechanisms leading to an increased production of Interferons (IFNs) and, in particular, of IFN-induced transmembrane protein 1 (IFITM1) and IFITM2. Indeed, it has been recently shown that IFITM2 is able to restrict SARS-CoV-2 entry occurring by endocytosis. In this regard, MB61222 may escape the antiviral activity of IFITMs by using the PM fusion pathway for entry into the target cell, whereas MB61° cannot escape this host antiviral response during MB61222 co-infection, since it has endocytosis as main pathway of entry. Altogether, our data support the evidence of quasispecies fighting for host dominance by taking benefit from the cell machinery to restrict the productive infection of competitors in the viral ensemble. This finding may explain, at least in part, the extraordinary rapid worldwide turnover of VOCs that use the PM fusion pathway to enter into target cells over the original pandemic strain.},\n\turldate = {2022-05-30},\n\tjournal = {Virus Evolution},\n\tauthor = {Caccuri, Francesca and Messali, Serena and Bortolotti, Daria and Di Silvestre, Dario and De Palma, Antonella and Cattaneo, Chiara and Bertelli, Anna and Zani, Alberto and Milanesi, Maria and Giovanetti, Marta and Campisi, Giovanni and Gentili, Valentina and Bugatti, Antonella and Filippini, Federica and Scaltriti, Erika and Pongolini, Stefano and Tucci, Alessandra and Fiorentini, Simona and d’Ursi, Pasqualina and Ciccozzi, Massimo and Mauri, Pierluigi and Rizzo, Roberta and Caruso, Arnaldo},\n\tmonth = may,\n\tyear = {2022},\n\tkeywords = {RNA sensing, SARS-CoV-2, interferons, prolonged infection, proteomic analysis, viral competition},\n\tpages = {veac042},\n}\n\n

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\n SARS-CoV-2 variants of concern (VOCs) emerge for their capability to better adapt to the human host aimed and enhance human-to-human transmission. Mutations in spike largely contributed to adaptation. Viral persistence is a prerequisite for intra-host virus evolution, and this likely occurred in immunocompromised patients who allow intra-host long-term viral replication. The underlying mechanism leading to the emergence of variants during viral persistence in the immunocompromised host is still unknown. Here we show the existence of an ensemble of minor mutants in the early biological samples obtained from an immunocompromised patient and their dynamic interplay with the master mutant during a persistent and productive long-term infection. In particular, after 222 days of active viral replication the original master mutant, named MB61°, was replaced by a minor quasispecies (MB61222) expressing two critical mutations in spike, namely Q493K and N501T. Isolation of the two viruses allowed us to show that MB61222 entry into target cells occurred mainly by the fusion at the plasma membrane (PM), whereas endocytosis characterized the entry mechanism used by MB61°. Interestingly, co-infection of two human cell lines of different origin with the SARS-CoV-2 isolates highlighted the early and dramatic predominance of MB61222 over MB61° replication. This finding may be explained by a faster replicative activity of MB61222 as compared to MB61° as well as by the capability of MB61222 to induce peculiar viral RNA sensing mechanisms leading to an increased production of Interferons (IFNs) and, in particular, of IFN-induced transmembrane protein 1 (IFITM1) and IFITM2. Indeed, it has been recently shown that IFITM2 is able to restrict SARS-CoV-2 entry occurring by endocytosis. In this regard, MB61222 may escape the antiviral activity of IFITMs by using the PM fusion pathway for entry into the target cell, whereas MB61° cannot escape this host antiviral response during MB61222 co-infection, since it has endocytosis as main pathway of entry. Altogether, our data support the evidence of quasispecies fighting for host dominance by taking benefit from the cell machinery to restrict the productive infection of competitors in the viral ensemble. This finding may explain, at least in part, the extraordinary rapid worldwide turnover of VOCs that use the PM fusion pathway to enter into target cells over the original pandemic strain.\n

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\n \n\n \n \n \n \n \n \n Novel homozygous mutations in the transcription factor NRL cause non-syndromic retinitis pigmentosa.\n \n \n \n \n\n\n \n El-Asrag, M. E.; Corton, M.; McKibbin, M.; Avila-Fernandez, A.; Mohamed, M. D.; Blanco-Kelly, F.; Toomes, C.; Inglehearn, C. F.; Ayuso, C.; and Ali, M.\n\n\n \n\n\n\n May 2022.\n Publisher: Molecular Vision\n\n\n\n
\n\n\n\n \n \n $\"Novel$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@misc{el-asrag_novel_2022,\n\ttitle = {Novel homozygous mutations in the transcription factor {NRL} cause non-syndromic retinitis pigmentosa},\n\turl = {http://www.molvis.org/molvis/v28/48/},\n\turldate = {2022-05-30},\n\tauthor = {El-Asrag, Mohammed E. and Corton, Marta and McKibbin, Martin and Avila-Fernandez, Almudena and Mohamed, Moin D. and Blanco-Kelly, Fiona and Toomes, Carmel and Inglehearn, Chris F. and Ayuso, Carmen and Ali, Manir},\n\tmonth = may,\n\tyear = {2022},\n\tnote = {Publisher: Molecular Vision},\n\tkeywords = {CES},\n}\n\n

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\n \n\n \n \n \n \n \n \n Unusual Clinical Manifestations in a Mexican Patient with Sanfilippo B Syndrome.\n \n \n \n \n\n\n \n Fernández-Hernández, L.; Reyna-Fabián, M. E.; Alcántara-Ortigoza, M. A.; Aláez-Verson, C.; Flores-Lagunes, L. L.; Carrillo-Sánchez, K.; and González-del Angel, A.\n\n\n \n\n\n\n Diagnostics, 12(5): 1268. May 2022.\n Number: 5 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Unusual$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{fernandez-hernandez_unusual_2022,\n\ttitle = {Unusual {Clinical} {Manifestations} in a {Mexican} {Patient} with {Sanfilippo} {B} {Syndrome}},\n\tvolume = {12},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2075-4418},\n\turl = {https://www.mdpi.com/2075-4418/12/5/1268},\n\tdoi = {10.3390/diagnostics12051268},\n\tabstract = {We present an unusual Mexican patient affected with mucopolysaccharidosis type IIIB (MPS IIIB; also called Sanfilippo B syndrome, MIM \\#252920) bearing clinical features that have not previously been described for MPS IIIB (growth arrest, hypogonadotropic hypogonadism, and congenital heart disease). Chromosomal microarray analysis was useful in identifying runs of homozygosity at 17q11.1–q21.33 and supporting the diagnosis of an underlying autosomal recessive condition. Sanger sequencing of NAGLU (17q21.2, MIM*609701) allowed us to identify a pathogenic homozygous p.(Arg234Cys) genotype. This NAGLU allele could be related to that previously described in an Iberian MPS IIIB founder haplotype; results from the polymorphic marker D17S800 and rs2071046 led us to hypothesize that it may have been introduced to Mexico through the Spanish settlement. The analysis of a clinical exome sequencing ruled out other monogenic etiologies for the previously undescribed clinical MPS IIIB manifestations. Our findings contribute to further delineating the MPS IIIB phenotype and suggest possible phenotype–genotype correlations.},\n\tlanguage = {en},\n\tnumber = {5},\n\turldate = {2022-05-30},\n\tjournal = {Diagnostics},\n\tauthor = {Fernández-Hernández, Liliana and Reyna-Fabián, Miriam Erandi and Alcántara-Ortigoza, Miguel Angel and Aláez-Verson, Carmen and Flores-Lagunes, Luis L. and Carrillo-Sánchez, Karol and González-del Angel, Ariadna},\n\tmonth = may,\n\tyear = {2022},\n\tnote = {Number: 5\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {CES v2, MPS IIIB, SOPHiA DDM, Sanfilippo B syndrome, clinical exome sequencing, growth arrest, sexual development, unusual manifestations},\n\tpages = {1268},\n}\n\n

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\n \n\n \n \n \n \n \n \n Genetic epidemiology of amyotrophic lateral sclerosis in Norway – a 2-year population based study.\n \n \n \n \n\n\n \n Olsen, C. G.; Busk, Ø. L.; Aanjesen, T. N.; Alstadhaug, K. B.; Bjørnå, I. K.; Braathen, G. J.; Breivik, K. L.; Demic, N.; Flemmen, H. Ø.; Hallerstig, E.; HogenEsch, I.; Holla, Ø. L.; Jøntvedt, A. B.; Kampman, M. T.; Kleveland, G.; Kvernmo, H. B.; Ljøstad, U.; Maniaol, A.; Morsund, Å. H.; Nakken, O.; Novy, C.; Rekand, T.; Schlüter, K.; Schuler, S.; Tveten, K.; Tysnes, O.; Holmøy, T.; and Høyer, H.\n\n\n \n\n\n\n Neuroepidemiology. May 2022.\n Publisher: Karger Publishers\n\n\n\n
\n\n\n\n \n \n $\"Genetic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{olsen_genetic_2022,\n\ttitle = {Genetic epidemiology of amyotrophic lateral sclerosis in {Norway} – a 2-year population based study},\n\tissn = {0251-5350, 1423-0208},\n\turl = {https://www.karger.com/Article/FullText/525091},\n\tdoi = {10.1159/000525091},\n\tabstract = {Abstract Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons. In Europe, disease-causing genetic variants have been identified in 40–70\\% of familial ALS patients and approximately in 5\\% of sporadic ALS patients. In Norway, the contribution of genetic variants to ALS has not yet been studied. In light of the potential development of personalized medicine, knowledge of genetic causes of ALS in a population is becoming increasingly important. The present study provides clinical and genetic data on familial and sporadic ALS patients in a Norwegian population-based cohort. Methods: Blood samples and clinical information from ALS patients were obtained at all 17 neurological departments throughout Norway during a 2-year period. Genetic analysis of the samples involved expansion analysis of C9orf72 and exome sequencing targeting 30 known ALS-linked genes. The variants were classified using genotype-phenotype correlations and bioinformatics tools. Results: A total of 279 ALS patients were included in the study. Of these, 11.5\\% had one or several family members affected with ALS, whereas 88.5\\% had no known family history of ALS. A genetic cause of ALS was identified in 31 individuals (11.1\\%), among which 18 (58.1\\%) were familial and 13 (41.9\\%) were sporadic. The most common genetic cause was the C9orf72 expansion (6.8\\%), which was identified in 8 familial and 11 sporadic ALS patients. Pathogenic or likely pathogenic variants of SOD1 and TBK1 were identified in 10 familial and 2 sporadic cases. C9orf72 expansions dominated in patients from the Northern and Central regions, whereas SOD1 variants dominated in patients from the South-Eastern region. Conclusion: In the present study, we identified several pathogenic gene variants in both familial and sporadic ALS patients. Restricting genetic analysis to only familial cases would miss more than 40 percent of those with a disease-causing genetic variant, indicating the need for genetic analysis in sporadic cases as well.},\n\tlanguage = {english},\n\turldate = {2022-05-30},\n\tjournal = {Neuroepidemiology},\n\tauthor = {Olsen, Cathrine Goberg and Busk, Øyvind Løvold and Aanjesen, Tori Navestad and Alstadhaug, Karl Bjørnar and Bjørnå, Ingrid Kristine and Braathen, Geir Julius and Breivik, Kristin Lif and Demic, Natasha and Flemmen, Heidi Øyen and Hallerstig, Erika and HogenEsch, Ineke and Holla, Øystein Lunde and Jøntvedt, Anne Berit and Kampman, Margitta T. and Kleveland, Grethe and Kvernmo, Helene Ballo and Ljøstad, Unn and Maniaol, Angelina and Morsund, Åse Hagen and Nakken, Ola and Novy, Camilla and Rekand, Tiina and Schlüter, Katrin and Schuler, Stephan and Tveten, Kristian and Tysnes, Ole-Bjørn and Holmøy, Trygve and Høyer, Helle},\n\tmonth = may,\n\tyear = {2022},\n\tpmid = {35576897},\n\tnote = {Publisher: Karger Publishers},\n\tkeywords = {Alamut},\n}\n\n

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\n Abstract Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons. In Europe, disease-causing genetic variants have been identified in 40–70% of familial ALS patients and approximately in 5% of sporadic ALS patients. In Norway, the contribution of genetic variants to ALS has not yet been studied. In light of the potential development of personalized medicine, knowledge of genetic causes of ALS in a population is becoming increasingly important. The present study provides clinical and genetic data on familial and sporadic ALS patients in a Norwegian population-based cohort. Methods: Blood samples and clinical information from ALS patients were obtained at all 17 neurological departments throughout Norway during a 2-year period. Genetic analysis of the samples involved expansion analysis of C9orf72 and exome sequencing targeting 30 known ALS-linked genes. The variants were classified using genotype-phenotype correlations and bioinformatics tools. Results: A total of 279 ALS patients were included in the study. Of these, 11.5% had one or several family members affected with ALS, whereas 88.5% had no known family history of ALS. A genetic cause of ALS was identified in 31 individuals (11.1%), among which 18 (58.1%) were familial and 13 (41.9%) were sporadic. The most common genetic cause was the C9orf72 expansion (6.8%), which was identified in 8 familial and 11 sporadic ALS patients. Pathogenic or likely pathogenic variants of SOD1 and TBK1 were identified in 10 familial and 2 sporadic cases. C9orf72 expansions dominated in patients from the Northern and Central regions, whereas SOD1 variants dominated in patients from the South-Eastern region. Conclusion: In the present study, we identified several pathogenic gene variants in both familial and sporadic ALS patients. Restricting genetic analysis to only familial cases would miss more than 40 percent of those with a disease-causing genetic variant, indicating the need for genetic analysis in sporadic cases as well.\n

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\n \n\n \n \n \n \n \n \n Spatial transcriptome of a germinal center plasmablastic burst hints at MYD88/CD79B mutants-enriched diffuse large B-cell lymphomas.\n \n \n \n \n\n\n \n L'Imperio, V.; Morello, G.; Vegliante, M. C.; Cancila, V.; Bertolazzi, G.; Mazzara, S.; Belmonte, B.; Mangogna, A.; Balzarini, P.; Corral, L.; Lopez, G.; Di Napoli, A.; Facchetti, F.; Pagni, F.; and Tripodo, C.\n\n\n \n\n\n\n European Journal of Immunology, n/a(n/a). May 2022.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/eji.202149746\n\n\n\n
\n\n\n\n \n \n $\"Spatial$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{limperio_spatial_2022,\n\ttitle = {Spatial transcriptome of a germinal center plasmablastic burst hints at {MYD88}/{CD79B} mutants-enriched diffuse large {B}-cell lymphomas},\n\tvolume = {n/a},\n\tissn = {1521-4141},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/eji.202149746},\n\tdoi = {10.1002/eji.202149746},\n\tabstract = {The germinal center (GC) reaction results in the selection of B-cells acquiring effector Ig secreting ability by progressing towards plasmablastic differentiation. This transition is associated with exclusion from the GC microenvironment. The aberrant expansion of plasmablastic elements within the GC fringes configures an atypical condition, the biological characteristics of which have not been defined yet. We investigated the in situ immunophenotypical and transcriptional characteristics of a non-clonal germinotropic expansion of plasmablastic elements (GEx) occurring in the tonsil of a young patient. Compared to neighboring GC and peri-follicular regions, the GEx showed a distinctive signature featuring key regulators of plasmacytic differentiation, cytokine signaling, and cell metabolism. The GEx signature was tested in the setting of diffuse large B-cell lymphoma (DLBCL) as a prototypical model of lymphomagenesis encompassing transformation at different stages of GC and post-GC functional differentiation. The signature outlined DLBCL clusters with different immune microenvironment composition and enrichment in genetic subtypes. This report represents the first insight into the transcriptional features of a germinotropic plasmablastic burst, shedding light into the molecular hallmarks of B cells undergoing plasmablastic differentiation and aberrant expansion within the non-canonical setting of the GC microenvironment. This article is protected by copyright. All rights reserved},\n\tlanguage = {en},\n\tnumber = {n/a},\n\turldate = {2022-05-17},\n\tjournal = {European Journal of Immunology},\n\tauthor = {L'Imperio, Vincenzo and Morello, Gaia and Vegliante, Maria Carmela and Cancila, Valeria and Bertolazzi, Giorgio and Mazzara, Saveria and Belmonte, Beatrice and Mangogna, Alessandro and Balzarini, Piera and Corral, Lilia and Lopez, Gianluca and Di Napoli, Arianna and Facchetti, Fabio and Pagni, Fabio and Tripodo, Claudio},\n\tmonth = may,\n\tyear = {2022},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/eji.202149746},\n\tkeywords = {B-cell, Diffuse, Digital, Germinal, LYS, Lymphoma, Plasmablast, center, large, profiling, spatial},\n}\n\n

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\n \n\n \n \n \n \n \n \n MO022: Digenic inheritance in Alport syndrome.\n \n \n \n \n\n\n \n del Mar Del Águila García, M.; Poyatos Andújar, A. M; Isabel Morales García, A.; Martínez Atienza, M.; García Linares, S.; and Jose Esteban de la Rosa, R.\n\n\n \n\n\n\n Nephrology Dialysis Transplantation, 37(Supplement_3): gfac062.003. May 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"MO022:$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{del_mar_del_aguila_garcia_mo022_2022,\n\ttitle = {{MO022}: {Digenic} inheritance in {Alport} syndrome},\n\tvolume = {37},\n\tissn = {0931-0509},\n\tshorttitle = {{MO022}},\n\turl = {https://doi.org/10.1093/ndt/gfac062.003},\n\tdoi = {10.1093/ndt/gfac062.003},\n\tabstract = {The approach to Alport syndrome is a difficult task due to the phenotypic variability of its symptomatology, incomplete penetrance and its different forms of inheritance [1].It presents a high degree of underdiagnosis, both because of erratic diagnosis as well as the existence of undiagnosed patients [2].This study shows a patient carrying two pathogenic variants in COL4A3 and COL4A4 genes, respectively. The interest of the case lies in the low reported frequency of this type of inheritance, of which there are still no prevalence studies, but which may help to better understand this entity, as well as aid future diagnoses [3, 4].Our index case is a 55-year-old male (IV.1). His medical history dates back to childhood when the disease began with microhematuria, repeated urinary tract infections, proteinuria and a progressive decrease in glomerular filtration rate until he required hemodialysis at 23 years. He received a living-renal transplantation from his mother, restarting hemodialysis at 49 years; a second engraftment was carried out 3 years later that was working for 5 years until a clear cell renal cancer was diagnosed and transplantectomy was required. There was no evidence of hearing or ocular impairment.Throughout the patient's follow-up, the existence of other relatives on the paternal side with kidney disease became known, and with the suspicion of hereditary origin, a genogram of the family was constructed with five generations [Figure 1].FIGURE 1:Family genogram.A genetic study was performed using a next-generation sequencing (NGS) panel (Sophia Genetics) covering the coding and splicing regions of 44 genes related to HRE (Table 1). Subsequently, the study was extended to other relatives.Table 1.Genes included in the Nephropathies solution panel of SOPHiA GeneticsAGXTCLCNKBEMP2NPHS2SLC12A1AQP2COL4A3EYA1NR3C2SLC12A3ATP6V0A4COLA4A4FN1OCRLSLC34A1ATP6V1B1COL4A5FOXC1PAX2SLC4A1AVPR2CRB2GRHPRPHEXSLC4A4BSNDCTNSHNF1bPKD1TTC21BCASRCUBNKAK2PKD2UMODCEP290CYP24A1KCNJ1PKHD1WT1CLN5DSTYKLAMB2SIX1Molecular analysis identified two probably pathogenic variants in our index case and other relative at the moment, both in heterozygosis, one in exon 48 of the COL4A3 gene: c.4421T \\&gt; C, p.(Leu1474Pro). This is a missense-type change in which thymine is replaced by cytosine at position 4421 of the coding sequence and predicts the substitution of the amino acid leucine by proline at position 1474 of the protein, affecting two functional domains. This variant is described and reported in the databases as pathogenic. On the other hand, it presents a deletion, also in heterozygosis, of exon 9 of the COL4A4 gene. Both variants were confirmed by Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA), respectively.In this family, the variants co-segregate with the disease, although the analysis of other cases would be useful; furthermore, both variants co-segregate together, which indicates that the variants are in cis and both come from the same branch and neither has a de novo origin.We have identified a case of digenic inheritance, two pathogenic variants in COL4A3 and COL4A4 genes respectively, thanks to the NGS techniques, of which very few cases have been described in the literature.Genetic analysis is the only way to confirm the diagnosis, often even to establish it after uncertain diagnoses; it is also the way to determine the mode of transmission and can often avoid the use of other invasive and not risk-free techniques such as skin or kidney biopsy.Although there is currently no curative treatment, early diagnosis is important to slow its progression, so that after the identification of a pathogenic variant, the family implications should be of special interest, to carry out adequate genetic counseling where family members at risk are informed and genetic study is offered, as well as the existing reproductive options for affected patients, such as preimplantation genetic testing or gamete donation. Otherwise, the offspring should be included in a program for early detection and monitoring of the disease.},\n\tnumber = {Supplement\\_3},\n\turldate = {2022-05-17},\n\tjournal = {Nephrology Dialysis Transplantation},\n\tauthor = {del Mar Del Águila García, María and Poyatos Andújar, Antonio M and Isabel Morales García, Ana and Martínez Atienza, Margarita and García Linares, Susana and Jose Esteban de la Rosa, Rafael},\n\tmonth = may,\n\tyear = {2022},\n\tkeywords = {Nephropathies, alport},\n\tpages = {gfac062.003},\n}\n\n

\n\n\n

\n The approach to Alport syndrome is a difficult task due to the phenotypic variability of its symptomatology, incomplete penetrance and its different forms of inheritance [1].It presents a high degree of underdiagnosis, both because of erratic diagnosis as well as the existence of undiagnosed patients [2].This study shows a patient carrying two pathogenic variants in COL4A3 and COL4A4 genes, respectively. The interest of the case lies in the low reported frequency of this type of inheritance, of which there are still no prevalence studies, but which may help to better understand this entity, as well as aid future diagnoses [3, 4].Our index case is a 55-year-old male (IV.1). His medical history dates back to childhood when the disease began with microhematuria, repeated urinary tract infections, proteinuria and a progressive decrease in glomerular filtration rate until he required hemodialysis at 23 years. He received a living-renal transplantation from his mother, restarting hemodialysis at 49 years; a second engraftment was carried out 3 years later that was working for 5 years until a clear cell renal cancer was diagnosed and transplantectomy was required. There was no evidence of hearing or ocular impairment.Throughout the patient's follow-up, the existence of other relatives on the paternal side with kidney disease became known, and with the suspicion of hereditary origin, a genogram of the family was constructed with five generations [Figure 1].FIGURE 1:Family genogram.A genetic study was performed using a next-generation sequencing (NGS) panel (Sophia Genetics) covering the coding and splicing regions of 44 genes related to HRE (Table 1). Subsequently, the study was extended to other relatives.Table 1.Genes included in the Nephropathies solution panel of SOPHiA GeneticsAGXTCLCNKBEMP2NPHS2SLC12A1AQP2COL4A3EYA1NR3C2SLC12A3ATP6V0A4COLA4A4FN1OCRLSLC34A1ATP6V1B1COL4A5FOXC1PAX2SLC4A1AVPR2CRB2GRHPRPHEXSLC4A4BSNDCTNSHNF1bPKD1TTC21BCASRCUBNKAK2PKD2UMODCEP290CYP24A1KCNJ1PKHD1WT1CLN5DSTYKLAMB2SIX1Molecular analysis identified two probably pathogenic variants in our index case and other relative at the moment, both in heterozygosis, one in exon 48 of the COL4A3 gene: c.4421T > C, p.(Leu1474Pro). This is a missense-type change in which thymine is replaced by cytosine at position 4421 of the coding sequence and predicts the substitution of the amino acid leucine by proline at position 1474 of the protein, affecting two functional domains. This variant is described and reported in the databases as pathogenic. On the other hand, it presents a deletion, also in heterozygosis, of exon 9 of the COL4A4 gene. Both variants were confirmed by Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA), respectively.In this family, the variants co-segregate with the disease, although the analysis of other cases would be useful; furthermore, both variants co-segregate together, which indicates that the variants are in cis and both come from the same branch and neither has a de novo origin.We have identified a case of digenic inheritance, two pathogenic variants in COL4A3 and COL4A4 genes respectively, thanks to the NGS techniques, of which very few cases have been described in the literature.Genetic analysis is the only way to confirm the diagnosis, often even to establish it after uncertain diagnoses; it is also the way to determine the mode of transmission and can often avoid the use of other invasive and not risk-free techniques such as skin or kidney biopsy.Although there is currently no curative treatment, early diagnosis is important to slow its progression, so that after the identification of a pathogenic variant, the family implications should be of special interest, to carry out adequate genetic counseling where family members at risk are informed and genetic study is offered, as well as the existing reproductive options for affected patients, such as preimplantation genetic testing or gamete donation. Otherwise, the offspring should be included in a program for early detection and monitoring of the disease.\n

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\n \n\n \n \n \n \n \n \n Detection of SF3B1 p.Lys700Glu Mutation by PNA-PCR Clamping in Myelodysplastic Syndromes and Myeloproliferative Neoplasms.\n \n \n \n \n\n\n \n Petiti, J.; Itri, F.; Signorino, E.; Frolli, A.; Fava, C.; Armenio, M.; Marini, S.; Giugliano, E.; Lo Iacono, M.; Saglio, G.; and Cilloni, D.\n\n\n \n\n\n\n Journal of Clinical Medicine, 11(5): 1267. February 2022.\n Number: 5 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Detection$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{petiti_detection_2022,\n\ttitle = {Detection of {SF3B1} p.{Lys700Glu} {Mutation} by {PNA}-{PCR} {Clamping} in {Myelodysplastic} {Syndromes} and {Myeloproliferative} {Neoplasms}},\n\tvolume = {11},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2077-0383},\n\turl = {https://www.mdpi.com/2077-0383/11/5/1267},\n\tdoi = {10.3390/jcm11051267},\n\tabstract = {Mutations in SF3B1 are found in 20\\% of myelodysplastic syndromes and 5–10\\% of myeloproliferative neoplasms, where they are considered important for diagnosis and therapy decisions. Sanger sequencing and NGS are the currently available methods to identify SF3B1 mutations, but both are time-consuming and expensive techniques that are not practicable in most small-/medium-sized laboratories. To identify the most frequent SF3B1 mutation, p.Lys700Glu, we developed a novel fast and cheap assay based on PNA-PCR clamping. After setting the optimal PCR conditions, the limit of detection of PNA-PCR clamping was evaluated, and the method allowed up to 0.1\\% of mutated SF3B1 to be identified. Successively, PNA-PCR clamping and Sanger sequencing were used to blind test 90 DNA from patients affected by myelodysplastic syndromes and myeloproliferative neoplasms for the SF3B1 p.Lys700Glu mutation. PNA-PCR clamping and Sanger sequencing congruently identified 75 negative and 13 positive patients. Two patients identified as positive by PNA-PCR clamping were missed by Sanger analysis. The discordant samples were analyzed by NGS, which confirmed the PNA-PCR clamping result, indicating that these samples contained the SF3B1 p.Lys700Glu mutation. This approach could easily increase the characterization of myelodysplastic syndromes and myeloproliferative neoplasms in small-/medium-sized laboratories, and guide patients towards more appropriate therapy.},\n\tlanguage = {en},\n\tnumber = {5},\n\turldate = {2022-03-10},\n\tjournal = {Journal of Clinical Medicine},\n\tauthor = {Petiti, Jessica and Itri, Federico and Signorino, Elisabetta and Frolli, Antonio and Fava, Carmen and Armenio, Marco and Marini, Silvia and Giugliano, Emilia and Lo Iacono, Marco and Saglio, Giuseppe and Cilloni, Daniela},\n\tmonth = feb,\n\tyear = {2022},\n\tnote = {Number: 5\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {MDS, MPN, MYS, PNA-PCR clamping, SF3B1, SOPHiA DDM, p.Lys700Glu},\n\tpages = {1267},\n}\n\n

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\n \n\n \n \n \n \n \n \n Technological Advances: CEBPA and FLT3 Internal Tandem Duplication Mutations Can be Reliably Detected by Next Generation Sequencing.\n \n \n \n \n\n\n \n Akabari, R.; Qin, D.; and Hussaini, M.\n\n\n \n\n\n\n Genes, 13(4): 630. April 2022.\n Number: 4 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Technological$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{akabari_technological_2022,\n\ttitle = {Technological {Advances}: {CEBPA} and {FLT3} {Internal} {Tandem} {Duplication} {Mutations} {Can} be {Reliably} {Detected} by {Next} {Generation} {Sequencing}},\n\tvolume = {13},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2073-4425},\n\tshorttitle = {Technological {Advances}},\n\turl = {https://www.mdpi.com/2073-4425/13/4/630},\n\tdoi = {10.3390/genes13040630},\n\tabstract = {Background: The detection of CEBPA and FLT3 mutations by next generation sequencing (NGS) is challenging due to high GC content and Internal Tandem Duplications (ITDs). Recent advances have been made to surmount these challenges. In this study, we compare three commercial kits and evaluate the performance of these more advanced hybrid-capture and AMP-chemistry based methods. Methods: Amplicon-based TSM 54-Gene Panel (Illumina) was evaluated against hybridization-capture SOPHiA Genetics MSP, OGT SureSeq, and AMP chemistry-based VariantPlex (Archer) for wet-lab workflow and data-analysis pipelines. Standard kit directions and commercial analysis pipelines were followed. Seven CEBPA and 10 FLT3-positive cases were identified that previously were missed on an amplicon NGS assay. The average reads, coverage uniformity, and the detection of CEBPA or FLT3 mutations were compared. Results: All three panels detected all 10 CEBPA mutations and all 10 FLT3 ITDs with 100\\% sensitivity. In addition, there was high concordance (100\\%) between all three panels detecting 47/47 confirmed variants in a set of core myeloid genes. Conclusions: The results show that the NGS assays are now able to reliably detect CEBPA mutations and FLT3 ITDs. These assays may allow foregoing additional orthogonal testing for CEBPA and FLT3.},\n\tlanguage = {en},\n\tnumber = {4},\n\turldate = {2022-04-11},\n\tjournal = {Genes},\n\tauthor = {Akabari, Ratilal and Qin, Dahui and Hussaini, Mohammad},\n\tmonth = apr,\n\tyear = {2022},\n\tnote = {Number: 4\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {AML, CEBPA, FLT3, Internal Tandem Duplication (ITD), MYS, SOPHiA DDM, next generation sequencing (NGS)},\n\tpages = {630},\n}\n\n

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\n \n\n \n \n \n \n \n \n Genetic, clinic and histopathologic characterization of BRCA-associated hereditary breast and ovarian cancer in southwestern Finland.\n \n \n \n \n\n\n \n Pallonen, T. A.; Lempiäinen, S. M. M.; Joutsiniemi, T. K.; Aaltonen, R. I.; Pohjola, P. E.; and Kankuri-Tammilehto, M. K.\n\n\n \n\n\n\n Scientific Reports, 12(1): 6704. April 2022.\n Number: 1 Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"Genetic,$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{pallonen_genetic_2022,\n\ttitle = {Genetic, clinic and histopathologic characterization of {BRCA}-associated hereditary breast and ovarian cancer in southwestern {Finland}},\n\tvolume = {12},\n\tcopyright = {2022 The Author(s)},\n\tissn = {2045-2322},\n\turl = {https://www.nature.com/articles/s41598-022-10519-y},\n\tdoi = {10.1038/s41598-022-10519-y},\n\tabstract = {We have analyzed the histopathological, clinical, and genetic characteristics in hereditary breast and ovarian cancer patients of counselled families from 1996 up to today in the southwestern Finland population. In this study we analyzed the incidence of different BRCA1 and BRCA2 pathogenic variants (PV). 1211 families were evaluated, and the families were classified as 38 BRCA1 families, 48 BRCA2 families, 689 non-BRCA families and 436 other counselled families (criteria for genetic testing was not met). In those families, the study consisted of 44 BRCA1 breast and/or ovarian cancer patients, 58 BRCA2 cancer patients, 602 non-BRCA patients and 328 other counselled patients. Breast cancer mean onset was 4.6 years earlier in BRCA1 carriers compared to BRCA2 (p = 0.07, a trend) and ovarian cancer onset almost 11 years earlier in BRCA1 families (p {\\textless} 0.05). In BRCA families the onset of ovarian cancer was later than 40 years, and BRCA2-origin breast cancer was seen as late as 78 years. The BRCA PV (9\\%) increases the risk for same patient having both ovarian and breast cancer with a twofold risk when compared to non-BRCA group (4\\%) (95\\% CI p {\\textless} 0.05). Triple-negativity in BRCA1 (42\\%) carriers is approximately 2.6 times vs more common than in BRCA2 carriers (16\\%) (p {\\textless} 0.05). The risk ratio for bilateral breast cancer is approximately four times when compared BRCA2 (17\\%) and other counselled patients’ group (4\\%) (p {\\textless} 0.05). 27\\% southwestern BRCA2-families have a unique PV, and correspondingly 39\\% of BRCA1-families. The results of this analysis allow improved prediction of cancer risk in high-risk hereditary breast and ovarian families in southwestern Finland and improve long term follow-up programs. According to the result it could be justified to have the discussion about prophylactic salpingo-oophorectomy by the age of 40 years. The possibility of late breast cancer onset in BRCA2 carriers supports the lifelong follow-up in BRCA carriers. Cancer onset is similar between BRCA2 carries and non-BRCA high-risk families. This study evaluated mutation profile of BRCA in southwestern Finland. In this study genotype–phenotype correlation was not found},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2022-05-10},\n\tjournal = {Scientific Reports},\n\tauthor = {Pallonen, Terhi Aino-Sofia and Lempiäinen, Salla Maria Matleena and Joutsiniemi, Titta Kristiina and Aaltonen, Riitta Irmeli and Pohjola, Pia Erika and Kankuri-Tammilehto, Minna Kristiina},\n\tmonth = apr,\n\tyear = {2022},\n\tnote = {Number: 1\nPublisher: Nature Publishing Group},\n\tkeywords = {Cancer, Genetics, SOPHiA DDM},\n\tpages = {6704},\n}\n\n

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\n We have analyzed the histopathological, clinical, and genetic characteristics in hereditary breast and ovarian cancer patients of counselled families from 1996 up to today in the southwestern Finland population. In this study we analyzed the incidence of different BRCA1 and BRCA2 pathogenic variants (PV). 1211 families were evaluated, and the families were classified as 38 BRCA1 families, 48 BRCA2 families, 689 non-BRCA families and 436 other counselled families (criteria for genetic testing was not met). In those families, the study consisted of 44 BRCA1 breast and/or ovarian cancer patients, 58 BRCA2 cancer patients, 602 non-BRCA patients and 328 other counselled patients. Breast cancer mean onset was 4.6 years earlier in BRCA1 carriers compared to BRCA2 (p = 0.07, a trend) and ovarian cancer onset almost 11 years earlier in BRCA1 families (p \\textless 0.05). In BRCA families the onset of ovarian cancer was later than 40 years, and BRCA2-origin breast cancer was seen as late as 78 years. The BRCA PV (9%) increases the risk for same patient having both ovarian and breast cancer with a twofold risk when compared to non-BRCA group (4%) (95% CI p \\textless 0.05). Triple-negativity in BRCA1 (42%) carriers is approximately 2.6 times vs more common than in BRCA2 carriers (16%) (p \\textless 0.05). The risk ratio for bilateral breast cancer is approximately four times when compared BRCA2 (17%) and other counselled patients’ group (4%) (p \\textless 0.05). 27% southwestern BRCA2-families have a unique PV, and correspondingly 39% of BRCA1-families. The results of this analysis allow improved prediction of cancer risk in high-risk hereditary breast and ovarian families in southwestern Finland and improve long term follow-up programs. According to the result it could be justified to have the discussion about prophylactic salpingo-oophorectomy by the age of 40 years. The possibility of late breast cancer onset in BRCA2 carriers supports the lifelong follow-up in BRCA carriers. Cancer onset is similar between BRCA2 carries and non-BRCA high-risk families. This study evaluated mutation profile of BRCA in southwestern Finland. In this study genotype–phenotype correlation was not found\n

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\n \n\n \n \n \n \n \n \n Integrative diagnosis of primary cutaneous large B-cell lymphomas supports the relevance of cell of origin profiling.\n \n \n \n \n\n\n \n Gros, A.; Menguy, S.; Bobée, V.; Ducharme, O.; Cassaigne, I. C.; Vergier, B.; Parrens, M.; Beylot-Barry, M.; Pham-Ledard, A.; Ruminy, P.; Jardin, F.; and Merlio, J.\n\n\n \n\n\n\n PLOS ONE, 17(4): e0266978. April 2022.\n Publisher: Public Library of Science\n\n\n\n
\n\n\n\n \n \n $\"Integrative$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{gros_integrative_2022,\n\ttitle = {Integrative diagnosis of primary cutaneous large {B}-cell lymphomas supports the relevance of cell of origin profiling},\n\tvolume = {17},\n\tissn = {1932-6203},\n\turl = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0266978},\n\tdoi = {10.1371/journal.pone.0266978},\n\tabstract = {Primary cutaneous large B-cell lymphomas (PCLBCL) represent a diagnostic challenge because they are classified as PCLBCL, leg type (PCLBCL, LT) or primary cutaneous follicle centre lymphoma, large cell (PCFCL, LC), which differ by prognosis and therapeutic requirement. Unclassified cases with discordant clinical presentations, morphologies, and immunophenotypes may be classified into the not otherwise specified (PCLBCL, NOS) category based on ancillary molecular analyses. Cell-of-origin profiling as germinal centre (GC) type or non-GC type by immunohistochemistry is not considered reproducible because of variable CD10 expression. In a series of 55 PCLBCL cases with {\\textgreater} 80\\% large cells, we reported 21 PCFCL, LC cases as GC-type and 27 PCLBCL, LT as non-GC-type; 7 cases were considered PCLBCL, NOS. Here, we demonstrate the accuracy of molecular profiling of PCLBCL as GC or non-GC type using a reverse transcriptase multiplex ligation assay (RT-MLPA). RT-MLPA classified the seven PCLBCL, NOS cases in accordance with their mutational profile. An integrative principal component analysis confirmed the main criteria and the relevance of genomic profiling of PCFCL, LC as GC-derived, and PCLBCL, LT as non-GC-derived. Both the cell-of-origin classification of PCLBCL and the integrative analysis identified two clinically relevant subgroups according to overall survival, which may help to standardize PCLBCL diagnosis and patient management.},\n\tlanguage = {en},\n\tnumber = {4},\n\turldate = {2022-04-27},\n\tjournal = {PLOS ONE},\n\tauthor = {Gros, Audrey and Menguy, Sarah and Bobée, Victor and Ducharme, Océane and Cassaigne, Isabelle Cirilo and Vergier, Béatrice and Parrens, Marie and Beylot-Barry, Marie and Pham-Ledard, Anne and Ruminy, Philippe and Jardin, Fabrice and Merlio, Jean-Philippe},\n\tmonth = apr,\n\tyear = {2022},\n\tnote = {Publisher: Public Library of Science},\n\tkeywords = {Alamut, B cells, Cancer detection and diagnosis, Frameshift mutation, Lung and intrathoracic tumors, Lymphoma, Mutation detection, Phenotypes, Principal component analysis},\n\tpages = {e0266978},\n}\n\n

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\n \n\n \n \n \n \n \n \n Non-Invasive Cancer Genotyping: A Single-Center Experience on The Challenges, Limitations, and Methods \\textbar Gazi Medical Journal.\n \n \n \n \n\n\n \n Sahin, I.; Saat, H.; Erdem, H.; and Bahsi, T.\n\n\n \n\n\n\n . March 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Non-Invasive$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 5 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{sahin_non-invasive_2022,\n\ttitle = {Non-{Invasive} {Cancer} {Genotyping}: {A} {Single}-{Center} {Experience} on {The} {Challenges}, {Limitations}, and {Methods} {\\textbar} {Gazi} {Medical} {Journal}},\n\tshorttitle = {Non-{Invasive} {Cancer} {Genotyping}},\n\turl = {https://medicaljournal.gazi.edu.tr/index.php/GMJ/article/view/3217},\n\tlanguage = {en-US},\n\turldate = {2022-04-27},\n\tauthor = {Sahin, Ibrahim and Saat, Hanife and Erdem, Haktan and Bahsi, Taha},\n\tmonth = mar,\n\tyear = {2022},\n\tkeywords = {SOPHiA DDM, oncology solution},\n}\n\n

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\n \n\n \n \n \n \n \n \n Loss of thymidine phosphorylase activity disrupts adipocyte differentiation and induces insulin-resistant lipoatrophic diabetes.\n \n \n \n \n\n\n \n Gautheron, J.; Lima, L.; Akinci, B.; Zammouri, J.; Auclair, M.; Ucar, S. K.; Ozen, S.; Altay, C.; Bax, B. E.; Nemazanyy, I.; Lenoir, V.; Prip-Buus, C.; Acquaviva-Bourdain, C.; Lascols, O.; Fève, B.; Vigouroux, C.; Noel, E.; and Jéru, I.\n\n\n \n\n\n\n BMC Medicine, 20(1): 95. March 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Loss$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{gautheron_loss_2022,\n\ttitle = {Loss of thymidine phosphorylase activity disrupts adipocyte differentiation and induces insulin-resistant lipoatrophic diabetes},\n\tvolume = {20},\n\tissn = {1741-7015},\n\turl = {https://doi.org/10.1186/s12916-022-02296-2},\n\tdoi = {10.1186/s12916-022-02296-2},\n\tabstract = {Thymidine phosphorylase (TP), encoded by the TYMP gene, is a cytosolic enzyme essential for the nucleotide salvage pathway. TP catalyzes the phosphorylation of the deoxyribonucleosides, thymidine and 2′-deoxyuridine, to thymine and uracil. Biallelic TYMP variants are responsible for Mitochondrial NeuroGastroIntestinal Encephalomyopathy (MNGIE), an autosomal recessive disorder characterized in most patients by gastrointestinal and neurological symptoms, ultimately leading to death. Studies on the impact of TYMP variants in cellular systems with relevance to the organs affected in MNGIE are still scarce and the role of TP in adipose tissue remains unexplored.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2022-04-11},\n\tjournal = {BMC Medicine},\n\tauthor = {Gautheron, Jérémie and Lima, Lara and Akinci, Baris and Zammouri, Jamila and Auclair, Martine and Ucar, Sema Kalkan and Ozen, Samim and Altay, Canan and Bax, Bridget E. and Nemazanyy, Ivan and Lenoir, Véronique and Prip-Buus, Carina and Acquaviva-Bourdain, Cécile and Lascols, Olivier and Fève, Bruno and Vigouroux, Corinne and Noel, Esther and Jéru, Isabelle},\n\tmonth = mar,\n\tyear = {2022},\n\tkeywords = {Alamut, SOPHiA DDM, TP, TYMP, Thymidine phosphorylase},\n\tpages = {95},\n}\n\n

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\n \n\n \n \n \n \n \n \n Re-evaluation of missense variant classifications in NF2.\n \n \n \n \n\n\n \n Sadler, K. V.; Rowlands, C. F.; Smith, P. T.; Hartley, C. L.; Bowers, N. L.; Roberts, N. Y.; Harris, J. L.; Wallace, A. J.; Evans, D. G.; Messiaen, L. M.; and Smith, M. J.\n\n\n \n\n\n\n Human Mutation, n/a(n/a). March 2022.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/humu.24370\n\n\n\n
\n\n\n\n \n \n $\"Re-evaluation$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{sadler_re-evaluation_2022,\n\ttitle = {Re-evaluation of missense variant classifications in {NF2}},\n\tvolume = {n/a},\n\tissn = {1098-1004},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/humu.24370},\n\tdoi = {10.1002/humu.24370},\n\tabstract = {Missense variants in the NF2 gene result in variable NF2 disease presentation. Clinical classification of missense variants often represents a challenge, due to lack of evidence for pathogenicity and function. This study provides a summary of NF2 missense variants, with variant classifications based on currently available evidence. NF2 missense variants were collated from pathology-associated databases and existing literature. Association for Clinical Genomic Sciences Best Practice Guidelines (2020) were followed in the application of evidence for variant interpretation and classification. The majority of NF2 missense variants remain classified as variants of uncertain significance. However, NF2 missense variants identified in gnomAD occurred at a consistent rate across the gene, while variants compiled from pathology-associated databases displayed differing rates of variation by exon of NF2. The highest rate of NF2 disease-associated variants was observed in exon 7, while lower rates were observed toward the C-terminus of the NF2 protein, merlin. Further phenotypic information associated with variants, alongside variant-specific functional analysis, is necessary for more definitive variant interpretation. Our data identified differences in frequency of NF2 missense variants by exon between gnomAD population data and NF2 disease-associated variants, suggesting a potential genotype-phenotype correlation; further work is necessary to substantiate this.},\n\tlanguage = {en},\n\tnumber = {n/a},\n\turldate = {2022-04-11},\n\tjournal = {Human Mutation},\n\tauthor = {Sadler, Katherine V. and Rowlands, Charlie F. and Smith, Philip T. and Hartley, Claire L. and Bowers, Naomi L. and Roberts, Nicola Y. and Harris, Jade L. and Wallace, Andrew J. and Evans, D. Gareth and Messiaen, Ludwine M. and Smith, Miriam J.},\n\tmonth = mar,\n\tyear = {2022},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/humu.24370},\n\tkeywords = {Alamut, NF2, classification guidelines, missense, neurofibromatosis type 2, variant classification},\n}\n\n

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\n \n\n \n \n \n \n \n \n Clonal haematopoiesis as a risk factor for therapy-related myeloid neoplasms in patients with chronic lymphocytic leukaemia treated with chemo-(immuno)therapy.\n \n \n \n \n\n\n \n Voso, M.; Pandzic, T.; Falconi, G.; Denčić-Fekete, M.; De Bellis, E.; Scarfo, L.; Ljungström, V.; Iskas, M.; Del Poeta, G.; Ranghetti, P.; Laidou, S.; Cristiano, A.; Plevova, K.; Imbergamo, S.; Engvall, M.; Zucchetto, A.; Salvetti, C.; Mauro, F. R.; Stavroyianni, N.; Cavelier, L.; Ghia, P.; Stamatopoulos, K.; Fabiani, E.; and Baliakas, P.\n\n\n \n\n\n\n British Journal of Haematology, n/a(n/a). March 2022.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/bjh.18129\n\n\n\n
\n\n\n\n \n \n $\"Clonal$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{voso_clonal_2022,\n\ttitle = {Clonal haematopoiesis as a risk factor for therapy-related myeloid neoplasms in patients with chronic lymphocytic leukaemia treated with chemo-(immuno)therapy},\n\tvolume = {n/a},\n\tissn = {1365-2141},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1111/bjh.18129},\n\tdoi = {10.1111/bjh.18129},\n\tabstract = {Clonal haematopoiesis of indeterminate potential (CHIP) may predispose for the development of therapy-related myeloid neoplasms (t-MN). Using target next-generation sequencing (t-NGS) panels and digital droplet polymerase chain reactions (ddPCR), we studied the myeloid gene mutation profiles of patients with chronic lymphocytic leukaemia (CLL) who developed a t-MN after treatment with chemo-(immuno)therapy. Using NGS, we detected a total of 30 pathogenic/likely pathogenic (P/LP) variants in 10 of 13 patients with a t-MN (77\\%, median number of variants for patient: 2, range 0–6). The prevalence of CHIP was then backtracked in paired samples taken at CLL diagnosis in eight of these patients. Six of them carried at least one CHIP-variant at the time of t-MN (median: 2, range: 1–5), and the same variants were present in the CLL sample in five cases. CHIP variants were present in 34 of 285 patients from a population-based CLL cohort, which translates into a significantly higher prevalence of CHIP in patients with a CLL who developed a t-MN, compared to the population-based cohort (5/8, 62.5\\% vs. 34/285, 12\\%, p = 0.0001). Our data show that CHIP may be considered as a novel parameter affecting treatment algorithms in patients with CLL, and highlight the potential of using chemo-free therapies in CHIP-positive cases.},\n\tlanguage = {en},\n\tnumber = {n/a},\n\turldate = {2022-03-15},\n\tjournal = {British Journal of Haematology},\n\tauthor = {Voso, Maria-Teresa and Pandzic, Tatjana and Falconi, Giulia and Denčić-Fekete, Marija and De Bellis, Eleonora and Scarfo, Lydia and Ljungström, Viktor and Iskas, Michail and Del Poeta, Giovanni and Ranghetti, Pamela and Laidou, Stamatia and Cristiano, Antonio and Plevova, Karla and Imbergamo, Silvia and Engvall, Marie and Zucchetto, Antonella and Salvetti, Chiara and Mauro, Francesca R. and Stavroyianni, Niki and Cavelier, Lucia and Ghia, Paolo and Stamatopoulos, Kostas and Fabiani, Emiliano and Baliakas, Panagiotis},\n\tmonth = mar,\n\tyear = {2022},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/bjh.18129},\n\tkeywords = {CHIP and FCR, CLL, MYS, t-MN},\n}\n\n

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\n \n\n \n \n \n \n \n \n A human paradigm of LHX4 and NR5A1 developmental gene interaction in the pituitary gland and ovary?.\n \n \n \n \n\n\n \n Giannakopoulos, A.; Sertedaki, A.; and Chrysis, D.\n\n\n \n\n\n\n European Journal of Human Genetics,1–4. March 2022.\n Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{giannakopoulos_human_2022,\n\ttitle = {A human paradigm of {LHX4} and {NR5A1} developmental gene interaction in the pituitary gland and ovary?},\n\tcopyright = {2022 The Author(s), under exclusive licence to European Society of Human Genetics},\n\tissn = {1476-5438},\n\turl = {https://www.nature.com/articles/s41431-022-01076-z},\n\tdoi = {10.1038/s41431-022-01076-z},\n\tabstract = {The pituitary gland, as a nodal component of the endocrine system, is responsible for the regulation of growth, reproduction, metabolism, and homeostasis. Although pituitary formation though the hierarchical action of different transcription factors is well studied in mouse models, there is little evidence of the analogous developmental processes in humans. Herein, we present a female patient with a phenotype that includes blepharoptosis–ptosis–epicanthus syndrome and premature ovarian failure. Clinical exome sequencing revealed two heterozygous variants in two genes, LHX4 (pathogenic) and NR5A1 (VUS) genes and no mutation in FOXL2 gene. We propose a model of genetic interaction between LHX4 and NR5A1 during pituitary and ovarian development that may lead to a similar phenotype mediated by reduced FOXL2 expression.},\n\tlanguage = {en},\n\turldate = {2022-03-15},\n\tjournal = {European Journal of Human Genetics},\n\tauthor = {Giannakopoulos, Aristeidis and Sertedaki, Amalia and Chrysis, Dionisios},\n\tmonth = mar,\n\tyear = {2022},\n\tnote = {Publisher: Nature Publishing Group},\n\tkeywords = {CES, Gene regulation, Pituitary diseases, SOPHiA DDM},\n\tpages = {1--4},\n}\n\n

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\n \n\n \n \n \n \n \n \n Immunohistochemical Evaluation of BAP1 Expression in Breast Cancer with Known BRCA1 and BRCA2 Mutations and Comparison with Histopathological Features.\n \n \n \n \n\n\n \n Çalım-Gürbüz, B.; Güvendir, İ.; Ünal, B.; Erdoğan-Durmuş, Ş.; Topal, C. S.; Ağaoğlu, N. B.; Doğanay, H. L.; Kızılboğa, T.; and Zemheri, I. E.\n\n\n \n\n\n\n International Journal of Surgical Pathology,10668969221085969. March 2022.\n Publisher: SAGE Publications Inc\n\n\n\n
\n\n\n\n \n \n $\"Immunohistochemical$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{calim-gurbuz_immunohistochemical_2022,\n\ttitle = {Immunohistochemical {Evaluation} of {BAP1} {Expression} in {Breast} {Cancer} with {Known} {BRCA1} and {BRCA2} {Mutations} and {Comparison} with {Histopathological} {Features}},\n\tissn = {1066-8969},\n\turl = {https://doi.org/10.1177/10668969221085969},\n\tdoi = {10.1177/10668969221085969},\n\tabstract = {Introduction. BRCA-mutated breast cancers have specific pathological characteristics. BAP1 is a tumor suppressor gene that is important in many cancers with different pathways. The relationship between BRCA1 mutation and BAP1 immunohistochemical staining is still unclear. Our aim is to determine whether BAP1 immunohistochemical expression indicates BRCA mutation status in breast carcinomas with specific pathological characteristics. In addition, we aim to determine the histopathological characteristics of tumors according to BRCA mutations. Methods. Histomorphology, molecular subtypes and BAP1 immunohistochemical expression patterns of the BRCA1/BRCA2 mutated and non-mutated tumors were evaluated. The BAP1 immunohistochemical stain was applied to nine tumor tissues with the BRCA1 mutation, six tumor tissues with the BRCA2 mutation, and 16 tumor tissues without any BRCA mutation. Pearson's chi square test and the Fisher Freeman Halton test were used to analyze the associations between the datas. The statistical significance was considered as P value of {\\textless}.05. Results. Immunohistochemical BAP1 loss was not detected in any mutated or non-mutated tumor group. BRCA1 mutated tumors had the statistically highest histopathological grade (P = .04) and BRCA1/2 mutated tumors had significant immunohistochemical triple negative expression pattern (P = .01). Conclusions. Intrinsic and histopathological characteristics may vary between BRCA1 mutated and non-BRCA1 mutated tumors. Also, BAP1 loss was not detected in BRCA mutated breast tumors because of several effects of BAP1 that are non-related with BRCA in the cell cycle.},\n\tlanguage = {en},\n\turldate = {2022-03-15},\n\tjournal = {International Journal of Surgical Pathology},\n\tauthor = {Çalım-Gürbüz, Begüm and Güvendir, İrem and Ünal, Büşra and Erdoğan-Durmuş, Şenay and Topal, Cumhur Selçuk and Ağaoğlu, Nihat Buğra and Doğanay, Hamdi Levent and Kızılboğa, Tuğba and Zemheri, Itır Ebru},\n\tmonth = mar,\n\tyear = {2022},\n\tnote = {Publisher: SAGE Publications Inc},\n\tkeywords = {BAP1, BRCA1, BRCA2, HCS, SOPHiA DDM, breast, cancer},\n\tpages = {10668969221085969},\n}\n\n

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\n \n\n \n \n \n \n \n \n Novel mutations in the HADHB gene causing a mild phenotype of mitochondrial trifunctional protein (MTP) deficiency.\n \n \n \n \n\n\n \n Ørstavik, K.; Arntzen, K. A.; Mathisen, P.; Backe, P. H.; Tangeraas, T.; Rasmussen, M.; Kristensen, E.; Van Ghelue, M.; Jonsrud, C.; and Bliksrud, Y. T.\n\n\n \n\n\n\n JIMD Reports, n/a(n/a). March 2022.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmd2.12276\n\n\n\n
\n\n\n\n \n \n $\"Novel$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{orstavik_novel_2022,\n\ttitle = {Novel mutations in the {HADHB} gene causing a mild phenotype of mitochondrial trifunctional protein ({MTP}) deficiency},\n\tvolume = {n/a},\n\tissn = {2192-8312},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/jmd2.12276},\n\tdoi = {10.1002/jmd2.12276},\n\tabstract = {Mitochondrial trifunctional protein (MTP) deficiency is an ultrarare hereditary recessive disorder causing a broad spectrum of phenotypes with lethal infantile cardiomyopathy at the most severe end. Attenuated forms with polyneuropathy have been reported combined with myoglobinuria or rhabdomyolysis as key features. We here report three young adults (two siblings) in which three variants in the HADHB-gene were identified. All three cases had a similar mild phenotype with axonal neuropathy and frequent intermittent weakness episodes but without myoglobinuria. Special dietary precautions were recommended to minimize complications especially during infections and other catabolic states. MTP deficiency is therefore an important differential diagnosis in patients with milder fluctuating neuromuscular symptoms. Take-home message Axonal neuropathy and recurrent muscular weakness without concomitant rhabdomyolysis may be due to MTP deficiency.},\n\tlanguage = {en},\n\tnumber = {n/a},\n\turldate = {2022-03-15},\n\tjournal = {JIMD Reports},\n\tauthor = {Ørstavik, Kristin and Arntzen, Kjell Arne and Mathisen, Per and Backe, Paul Hoff and Tangeraas, Trine and Rasmussen, Magnhild and Kristensen, Erle and Van Ghelue, Marijke and Jonsrud, Christoffer and Bliksrud, Yngve Thomas},\n\tmonth = mar,\n\tyear = {2022},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmd2.12276},\n\tkeywords = {Alamut, HADHB, MTP, mutation, neuropathy, weakness},\n}\n\n

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\n \n\n \n \n \n \n \n \n Response prediction in patients with gastric and esophagogastric adenocarcinoma under neoadjuvant chemotherapy using targeted gene expression analysis and next-generation sequencing in pre-therapeutic biopsies.\n \n \n \n \n\n\n \n Kleo, K.; Jovanovic, V. M.; Arndold, A.; Lehmann, A.; Lammert, H.; Berg, E.; Harloff, H.; Treese, C.; Hummel, M.; and Daum, S.\n\n\n \n\n\n\n Journal of Cancer Research and Clinical Oncology. March 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Response$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{kleo_response_2022,\n\ttitle = {Response prediction in patients with gastric and esophagogastric adenocarcinoma under neoadjuvant chemotherapy using targeted gene expression analysis and next-generation sequencing in pre-therapeutic biopsies},\n\tissn = {1432-1335},\n\turl = {https://doi.org/10.1007/s00432-022-03944-z},\n\tdoi = {10.1007/s00432-022-03944-z},\n\tabstract = {Perioperative chemo-(radio-) therapy is the accepted standard in European patients with locally advanced adenocarcinoma of the esophagogastric junction or stomach (AEG/AS). However, 30–85\\% of patients do not respond to this treatment. The aim of our study was the identification of predictive biomarkers in pre-therapeutic endoscopic tumor biopsies from patients with histopathologic response (Becker-1) versus non-response (Becker-2/3) to preoperative chemotherapy.},\n\tlanguage = {en},\n\turldate = {2022-03-15},\n\tjournal = {Journal of Cancer Research and Clinical Oncology},\n\tauthor = {Kleo, Karsten and Jovanovic, Vladimir M. and Arndold, Alexander and Lehmann, Annika and Lammert, Hedwig and Berg, Erika and Harloff, Hannah and Treese, Christoph and Hummel, Michael and Daum, Severin},\n\tmonth = mar,\n\tyear = {2022},\n\tkeywords = {SOPHiA DDM},\n}\n\n

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\n \n\n \n \n \n \n \n \n Homozygosity for a novel INHA mutation in two male siblings with hypospadias, primary hypogonadism, and high normal testicular volume.\n \n \n \n \n\n\n \n Ateş, E. A.; Eltan, M.; Sahin, B.; Tosun, B. G.; Menevse, T. S.; Geckinli, B. B.; Greenfield, A.; Turan, S.; Bereket, A.; and Güran, T.\n\n\n \n\n\n\n European Journal of Endocrinology, -1(aop). March 2022.\n Publisher: Bioscientifica Ltd. Section: European Journal of Endocrinology\n\n\n\n
\n\n\n\n \n \n $\"Homozygosity$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{ates_homozygosity_2022,\n\ttitle = {Homozygosity for a novel {INHA} mutation in two male siblings with hypospadias, primary hypogonadism, and high normal testicular volume},\n\tvolume = {-1},\n\tissn = {0804-4643, 1479-683X},\n\turl = {https://eje.bioscientifica.com/view/journals/eje/aop/eje-21-1230/eje-21-1230.xml},\n\tdoi = {10.1530/EJE-21-1230},\n\tabstract = {Background: The human INHA gene encodes the inhibin subunit alpha protein, which is common to both inhibin A and B. The functional importance of inhibins in male sex development, sexual function, and reproduction remain largely unknown. Objective: We report for the first time two male siblings with homozygous INHA mutations. Methods: The medical files were examined for clinical, biochemical, and imaging data. Genetic analysis was performed using next-generation and Sanger sequencing methods. Results: Two brothers complained of gynecomastia, testicular pain, and had a history of hypospadias. Biochemistry revealed low serum testosterone, high gonadotropin and anti-Mullerian hormone, and very low/undetectable inhibin concentrations, where available. Both patients had azoospermia in spermiogram. We have identified a homozygous 2bp deletion (c.208\\_209delAG, R70Gfs*3) variant, which leads to a truncated INHA protein in both patients, and confirmed heterozygosity in the parents. The external genital development, pubertal onset and progression, reproductive functions, serum gonadotropins, and sex hormones of mother and father, who were heterozygous carriers of the identified mutation, were normal. Conclusion: Homozygosity for INHA mutations causes decreased prenatal and postnatal testosterone production and infertility in males, while the heterozygous female and male carriers of INHA mutations do not have any abnormality in sex development and reproduction.},\n\tlanguage = {en},\n\tnumber = {aop},\n\turldate = {2022-03-15},\n\tjournal = {European Journal of Endocrinology},\n\tauthor = {Ateş, Esra Arslan and Eltan, Mehmet and Sahin, Bahadir and Tosun, Busra Gurpinar and Menevse, Tuba Seven and Geckinli, Bilgen Bilge and Greenfield, Andy and Turan, Serap and Bereket, Abdullah and Güran, Tülay},\n\tmonth = mar,\n\tyear = {2022},\n\tnote = {Publisher: Bioscientifica Ltd.\nSection: European Journal of Endocrinology},\n\tkeywords = {CES, SOPHiA DDM, WES},\n}\n\n

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\n \n\n \n \n \n \n \n \n Determining the accuracy of next generation sequencing based copy number variation analysis in Hereditary Breast and Ovarian Cancer.\n \n \n \n \n\n\n \n Agaoglu, N. B.; Unal, B.; Akgun Dogan, O.; Zolfagharian, P.; Sharifli, P.; Karakurt, A.; Can Senay, B.; Kizilboga, T.; Yildiz, J.; Dinler Doganay, G.; and Doganay, L.\n\n\n \n\n\n\n Expert Review of Molecular Diagnostics, 0(0): 1–8. March 2022.\n Publisher: Taylor & Francis _eprint: https://doi.org/10.1080/14737159.2022.2048373\n\n\n\n
\n\n\n\n \n \n $\"Determining$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{agaoglu_determining_2022,\n\ttitle = {Determining the accuracy of next generation sequencing based copy number variation analysis in {Hereditary} {Breast} and {Ovarian} {Cancer}},\n\tvolume = {0},\n\tissn = {1473-7159},\n\turl = {https://doi.org/10.1080/14737159.2022.2048373},\n\tdoi = {10.1080/14737159.2022.2048373},\n\tabstract = {Background Copy number variations (CNVs) are commonly associated with malignancies, including hereditary breast and ovarian cancers. Next generation sequencing (NGS) provides solutions for CNV detection in a single run. This study aimed to compare the accuracy of CNV detection by NGS analyzing tool against Multiplex Ligation Dependent Probe Amplification (MLPA).Research design and methods In total, 1276 cases were studied by targeted NGS panels and 691 cases (61 calls in 58 NGS-CNV positive and 633 NGS-CNV negative cases) were validated by MLPA.Results Twenty-eight (46\\%) NGS-CNV positive calls were consistent, whereas 33 (54\\%) calls showed discordance with MLPA. Two cases were detected as SNV by the NGS and CNV by the MLPA analysis. In total, 2\\% of the cases showed an MLPA confirmed CNV region in BRCA1/2. The results of this study showed that despite the high false positive call rate of the NGS-CNV algorithm, there were no false negative calls. The cases that were determined to be negative by the NGS and positive by the MLPA were actually carrying SNVs that were located on the MLPA probe binding sites.Conclusion The diagnostic performance of NGS-CNV analysis is promising; however, the need for confirmation by different methods remains.},\n\tnumber = {0},\n\turldate = {2022-03-15},\n\tjournal = {Expert Review of Molecular Diagnostics},\n\tauthor = {Agaoglu, Nihat Bugra and Unal, Busra and Akgun Dogan, Ozlem and Zolfagharian, Payam and Sharifli, Pari and Karakurt, Aylin and Can Senay, Burak and Kizilboga, Tugba and Yildiz, Jale and Dinler Doganay, Gizem and Doganay, Levent},\n\tmonth = mar,\n\tyear = {2022},\n\tpmid = {35240897},\n\tnote = {Publisher: Taylor \\& Francis\n\\_eprint: https://doi.org/10.1080/14737159.2022.2048373},\n\tkeywords = {BRCA1, BRCA2, Next generation sequencing, SOPHiA DDM, copy number variation, multiplex ligation dependent amplification},\n\tpages = {1--8},\n}\n\n

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\n \n\n \n \n \n \n \n \n Next step in molecular genetics of hereditary breast/ovarian cancer: Multigene panel testing in clinical actionably genes and prioritization algorithms in the study of variants of uncertain significance.\n \n \n \n \n\n\n \n Castillo-Guardiola, V.; Rosado-Jiménez, L.; Sarabia-Meseguer, M. D.; Marín-Vera, M.; Macías-Cerrolaza, J. A.; García-Hernández, R.; Zafra-Poves, M.; Sánchez-Henarejos, P.; Moreno-Locubiche, M. Á.; Cuevas-Tortosa, E.; Arnaldos-Carrillo, M.; Ayala de la Peña, F.; Alonso-Romero, J. L.; Noguera-Velasco, J. A.; and Ruiz-Espejo, F.\n\n\n \n\n\n\n European Journal of Medical Genetics, 65(4): 104468. March 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Next$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{castillo-guardiola_next_2022,\n\ttitle = {Next step in molecular genetics of hereditary breast/ovarian cancer: {Multigene} panel testing in clinical actionably genes and prioritization algorithms in the study of variants of uncertain significance},\n\tvolume = {65},\n\tissn = {1769-7212},\n\tshorttitle = {Next step in molecular genetics of hereditary breast/ovarian cancer},\n\turl = {https://www.sciencedirect.com/science/article/pii/S1769721222000490},\n\tdoi = {10.1016/j.ejmg.2022.104468},\n\tabstract = {Introduction\nBRCA1 and BRCA2 are the two main genes causing hereditary breast and ovarian cancer (HBOC). However, thanks to the development of Next Generation Sequencing (NGS), other genes linked to this syndrome (CHEK2, BRIP1, ATM and PALB2 among others) can be analysed.\nMaterial and methods\nan analysis by multigene panel testing was performed in 138 index cases (ICs) from HBOC Spanish families with a previous non-informative result for BRCA1/2. The BRCA Hereditary Cancer Master™ Plus kit, including 26 actionable and candidate genes related to HBOC was employed. Once classified, an algorithm was employed to prioritized those variants of unknown significance with a higher risk of having a deleterious effect. Moreover, a mRNA splicing assay was performed for the prioritized VUS c.3402+3A {\\textgreater} C in ATM, located at intron 23.\nResults\nA total of 82 variants were found: 70 VUS and 12 pathogenic or probably pathogenic variants. The diagnostic yield in actionable genes non-BRCA was 7.97\\% of the total tested ICs. Overall, 19 VUS were prioritized, which meant 27\\% of the 70 total VUS. RNA analysis of the variant 3402+3A {\\textgreater} C confirmed a deleterious impact on splicing.\nDiscussion\nThe implementation of a multigene panel in HBOC studied families improved the diagnostic yield, concordant with results obtained in previous publications. Due to the important number of VUS obtained in NGS, the application of a prioritization algorithm is needed in order to select those variants in which it is necessary to conduct further studies.},\n\tlanguage = {en},\n\tnumber = {4},\n\turldate = {2022-03-15},\n\tjournal = {European Journal of Medical Genetics},\n\tauthor = {Castillo-Guardiola, Verónica and Rosado-Jiménez, Laura and Sarabia-Meseguer, María Desamparados and Marín-Vera, Miguel and Macías-Cerrolaza, José Antonio and García-Hernández, Rosario and Zafra-Poves, Marta and Sánchez-Henarejos, Pilar and Moreno-Locubiche, María Ángeles and Cuevas-Tortosa, Encarnación and Arnaldos-Carrillo, María and Ayala de la Peña, Francisco and Alonso-Romero, José Luis and Noguera-Velasco, José Antonio and Ruiz-Espejo, Francisco},\n\tmonth = mar,\n\tyear = {2022},\n\tkeywords = {Clinical actionability, HBOC, Multigene panel testing, Prioritization algorithm},\n\tpages = {104468},\n}\n\n

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\n \n\n \n \n \n \n \n \n A Novel Benchmarking Approach to Assess the Agreement among Radiomic Tools.\n \n \n \n \n\n\n \n Bettinelli, A.; Marturano, F.; Avanzo, M.; Loi, E.; Menghi, E.; Mezzenga, E.; Pirrone, G.; Sarnelli, A.; Strigari, L.; Strolin, S.; and Paiusco, M.\n\n\n \n\n\n\n Radiology,211604. March 2022.\n Publisher: Radiological Society of North America\n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 7 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{bettinelli_novel_2022,\n\ttitle = {A {Novel} {Benchmarking} {Approach} to {Assess} the {Agreement} among {Radiomic}                     {Tools}},\n\tissn = {0033-8419},\n\turl = {https://pubs.rsna.org/doi/full/10.1148/radiol.211604},\n\tdoi = {10.1148/radiol.211604},\n\tabstract = {Background\n\nThe translation of radiomic models into clinical practice is hindered by the limited reproducibility of features across software and studies. Standardization is needed to accelerate this process and to bring radiomics closer to clinical deployment.\n\nPurpose\n\nTo assess the standardization level of seven radiomic software programs and investigate software agreement as a function of built-in image preprocessing (eg, interpolation and discretization), feature aggregation methods, and the morphological characteristics (ie, volume and shape) of the region of interest (ROI).\n\nMaterials and Methods\n\nThe study was organized into two phases: In phase I, the two Image Biomarker Standardization Initiative (IBSI) phantoms were used to evaluate the IBSI compliance of seven software programs. In phase II, the reproducibility of all IBSI-standardized radiomic features across tools was assessed with two custom Italian multicenter Shared Understanding of Radiomic Extractors (ImSURE) digital phantoms that allowed, in conjunction with a systematic feature extraction, observations on whether and how feature matches between program pairs varied depending on the preprocessing steps, aggregation methods, and ROI characteristics.\n\nResults\n\nIn phase I, the software programs showed different levels of completeness (ie, the number of computable IBSI benchmark values). However, the IBSI-compliance assessment revealed that they were all standardized in terms of feature implementation. When considering additional preprocessing steps, for each individual program, match percentages fell by up to 30\\%. In phase II, the ImSURE phantoms showed that software agreement was dependent on discretization and aggregation as well as on ROI shape and volume factors.\n\nConclusion\n\nThe agreement of radiomic software varied in relation to factors that had already been standardized (eg, interpolation and discretization methods) and factors that need standardization. Both dependences must be resolved to ensure the reproducibility of radiomic features and to pave the way toward the clinical adoption of radiomic models.\n\nPublished under a CC BY 4.0 license.\n\nOnline supplemental material is available for this article.\n\nSee also the editorial by Steiger in this issue.\n\nAn earlier incorrect version appeared online and in print. This article was corrected on March 2, 2022.},\n\turldate = {2022-03-15},\n\tjournal = {Radiology},\n\tauthor = {Bettinelli, Andrea and Marturano, Francesca and Avanzo, Michele and Loi, Emiliano and Menghi, Enrico and Mezzenga, Emilio and Pirrone, Giovanni and Sarnelli, Anna and Strigari, Lidia and Strolin, Silvia and Paiusco, Marta},\n\tmonth = mar,\n\tyear = {2022},\n\tnote = {Publisher: Radiological Society of North America},\n\tkeywords = {Radiomics, SOPHiA DDM},\n\tpages = {211604},\n}\n\n

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\n Background The translation of radiomic models into clinical practice is hindered by the limited reproducibility of features across software and studies. Standardization is needed to accelerate this process and to bring radiomics closer to clinical deployment. Purpose To assess the standardization level of seven radiomic software programs and investigate software agreement as a function of built-in image preprocessing (eg, interpolation and discretization), feature aggregation methods, and the morphological characteristics (ie, volume and shape) of the region of interest (ROI). Materials and Methods The study was organized into two phases: In phase I, the two Image Biomarker Standardization Initiative (IBSI) phantoms were used to evaluate the IBSI compliance of seven software programs. In phase II, the reproducibility of all IBSI-standardized radiomic features across tools was assessed with two custom Italian multicenter Shared Understanding of Radiomic Extractors (ImSURE) digital phantoms that allowed, in conjunction with a systematic feature extraction, observations on whether and how feature matches between program pairs varied depending on the preprocessing steps, aggregation methods, and ROI characteristics. Results In phase I, the software programs showed different levels of completeness (ie, the number of computable IBSI benchmark values). However, the IBSI-compliance assessment revealed that they were all standardized in terms of feature implementation. When considering additional preprocessing steps, for each individual program, match percentages fell by up to 30%. In phase II, the ImSURE phantoms showed that software agreement was dependent on discretization and aggregation as well as on ROI shape and volume factors. Conclusion The agreement of radiomic software varied in relation to factors that had already been standardized (eg, interpolation and discretization methods) and factors that need standardization. Both dependences must be resolved to ensure the reproducibility of radiomic features and to pave the way toward the clinical adoption of radiomic models. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Steiger in this issue. An earlier incorrect version appeared online and in print. This article was corrected on March 2, 2022.\n

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\n \n\n \n \n \n \n \n \n Exploring the relevance of NUP93 variants in steroid-resistant nephrotic syndrome using next generation sequencing and a fly kidney model.\n \n \n \n \n\n\n \n Bierzynska, A.; Bull, K.; Miellet, S.; Dean, P.; Neal, C.; Colby, E.; McCarthy, H. J.; Hegde, S.; Sinha, M. D.; Bugarin Diz, C.; Stirrups, K.; Megy, K.; Mapeta, R.; Penkett, C.; Marsh, S.; Forrester, N.; Afzal, M.; Stark, H.; BioResource, N.; Williams, M.; Welsh, G. I.; Koziell, A. B.; Hartley, P. S.; and Saleem, M. A.\n\n\n \n\n\n\n Pediatric Nephrology. February 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Exploring$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{bierzynska_exploring_2022,\n\ttitle = {Exploring the relevance of {NUP93} variants in steroid-resistant nephrotic syndrome using next generation sequencing and a fly kidney model},\n\tissn = {1432-198X},\n\turl = {https://doi.org/10.1007/s00467-022-05440-5},\n\tdoi = {10.1007/s00467-022-05440-5},\n\tabstract = {Variants in genes encoding nuclear pore complex (NPC) proteins are a newly identified cause of paediatric steroid-resistant nephrotic syndrome (SRNS). Recent reports describing NUP93 variants suggest these could be a significant cause of paediatric onset SRNS. We report NUP93 cases in the UK and demonstrate in vivo functional effects of Nup93 depletion in a fly (Drosophila melanogaster) nephrocyte model.},\n\tlanguage = {en},\n\turldate = {2022-03-10},\n\tjournal = {Pediatric Nephrology},\n\tauthor = {Bierzynska, Agnieszka and Bull, Katherine and Miellet, Sara and Dean, Philip and Neal, Chris and Colby, Elizabeth and McCarthy, Hugh J. and Hegde, Shivaram and Sinha, Manish D. and Bugarin Diz, Carmen and Stirrups, Kathleen and Megy, Karyn and Mapeta, Rutendo and Penkett, Chris and Marsh, Sarah and Forrester, Natalie and Afzal, Maryam and Stark, Hannah and BioResource, NIHR and Williams, Maggie and Welsh, Gavin I. and Koziell, Ania B. and Hartley, Paul S. and Saleem, Moin A.},\n\tmonth = feb,\n\tyear = {2022},\n\tkeywords = {Alamut},\n}\n\n

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\n \n\n \n \n \n \n \n \n Phenotypic Variation in Vietnamese Osteogenesis Imperfecta Patients Sharing a Recessive P3H1 Pathogenic Variant.\n \n \n \n \n\n\n \n Zhytnik, L.; Duy, B. H.; Eekhoff, M.; Wisse, L.; Pals, G.; Reimann, E.; Kõks, S.; Märtson, A.; Maugeri, A.; Maasalu, K.; and Micha, D.\n\n\n \n\n\n\n Genes, 13(3): 407. February 2022.\n Number: 3 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Phenotypic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{zhytnik_phenotypic_2022,\n\ttitle = {Phenotypic {Variation} in {Vietnamese} {Osteogenesis} {Imperfecta} {Patients} {Sharing} a {Recessive} {P3H1} {Pathogenic} {Variant}},\n\tvolume = {13},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2073-4425},\n\turl = {https://www.mdpi.com/2073-4425/13/3/407},\n\tdoi = {10.3390/genes13030407},\n\tabstract = {Osteogenesis imperfecta (OI) is a syndromic disorder of bone fragility with high variation in its clinical presentation. Equally variable is molecular aetiology; recessive forms are caused by approximately 20 different genes, many of which are directly implicated in collagen type I biosynthesis. Biallelic variants in prolyl 3-hydroxylase 1 (P3H1) are known to cause severe OI by affecting the competence of the prolyl 3-hydroxylation—cartilage associated protein—peptidyl-prolyl cis-trans isomerase B (P3H1-CRTAP-CyPB) complex, which acts on the Pro986 residue of collagen type I α 1 (COL1A1) and Pro707 collagen type I α 2 (COL1A2) chains. The investigation of an OI cohort of 146 patients in Vietnam identified 14 families with P3H1 variants. The c.1170+5G{\\textgreater}C variant was found to be very prevalent (12/14) and accounted for 10.3\\% of the Vietnamese OI cohort. New P3H1 variants were also identified in this population. Interestingly, the c.1170+5G{\\textgreater}C variants were found in families with the severe clinical Sillence types 2 and 3 but also the milder types 1 and 4. This is the first time that OI type 1 is reported in patients with P3H1 variants expanding the clinical spectrum. Patients with a homozygous c.1170+5G{\\textgreater}C variant shared severe progressively deforming OI type 3: bowed long bones, deformities of ribcage, long phalanges and hands, bluish sclera, brachycephaly, and early intrauterine fractures. Although it remains unclear if the c.1170+5G{\\textgreater}C variant constitutes a founder mutation in the Vietnamese population, its prevalence makes it valuable for the molecular diagnosis of OI in patients of the Kinh ethnicity. Our study provides insight into the clinical and genetic variation of P3H1-related OI in the Vietnamese population.},\n\tlanguage = {en},\n\tnumber = {3},\n\turldate = {2022-03-10},\n\tjournal = {Genes},\n\tauthor = {Zhytnik, Lidiia and Duy, Binh Ho and Eekhoff, Marelise and Wisse, Lisanne and Pals, Gerard and Reimann, Ene and Kõks, Sulev and Märtson, Aare and Maugeri, Alessandra and Maasalu, Katre and Micha, Dimitra},\n\tmonth = feb,\n\tyear = {2022},\n\tnote = {Number: 3\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Alamut, P3H1, bone dysplasia, genotype-phenotype correlation, next-generation sequencing, rare disorders, rare skeletal disease, recessive osteogenesis imperfecta},\n\tpages = {407},\n}\n\n

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\n \n\n \n \n \n \n \n \n Benefits and outcomes of a new multidisciplinary approach for the management and financing of sudden unexplained death cases in a forensic setting in Switzerland.\n \n \n \n \n\n\n \n Neubauer, J.; Kissel, C. K.; Bolliger, S. A.; Barbon, D.; Thali, M. J.; Kloiber, D.; Bode, P. K.; Kovacs, B.; Graf, U.; Maspoli, A.; Berger, W.; Saguner, A. M.; and Haas, C.\n\n\n \n\n\n\n Forensic Science International, 334: 111240. February 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Benefits$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{neubauer_benefits_2022,\n\ttitle = {Benefits and outcomes of a new multidisciplinary approach for the management and financing of sudden unexplained death cases in a forensic setting in {Switzerland}},\n\tvolume = {334},\n\tissn = {0379-0738},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0379073822000706},\n\tdoi = {10.1016/j.forsciint.2022.111240},\n\tabstract = {Sudden cardiac death (SCD) is an important public health issue. In young persons aged between 1 and 40 years, most SCDs are caused by potentially inherited cardiac diseases, often not detectable during conventional medico-legal investigations and therefore termed as sudden unexplained deaths (SUD). In this study, we describe the implementation, feasibility and importance of a standardized procedure to investigate SUD cases within the forensic framework at the Zurich Institute of Forensic Medicine in Switzerland. This new approach involves a multidisciplinary collaboration including forensic autopsy, second pathology expert opinion, post-mortem molecular genetic testing, cardiac counselling of relatives, and a tentative financing. This procedure is in line with the published Swiss and European recommendations on the management of SCDs. During a two-year pilot project, 39 sudden and unexpected death cases were collected, whereof 10 deceased remained without any identifiable cause of death after medico-legal investigation and second expert evaluation. Molecular autopsy, including 393 genes involved in cardio-vascular and metabolic diseases, identified eight pathogenic or likely pathogenic genetic variants in five out of the 10 deceased (50\\%). Cardio-genetic follow-up investigations in the families of the 10 deceased revealed phenotype-positive relatives in four families and required specific therapies, including an implantable cardioverter defibrillator (ICD) for primary prevention. Multidisciplinary collaboration is crucial for an optimal management of sudden unexplained death cases, to identify additional relatives at risk, and to prevent other tragic deaths within a family.},\n\tlanguage = {en},\n\turldate = {2022-03-10},\n\tjournal = {Forensic Science International},\n\tauthor = {Neubauer, Jacqueline and Kissel, Christine K. and Bolliger, Stephan A. and Barbon, Daniela and Thali, Michael J. and Kloiber, Daniel and Bode, Peter K. and Kovacs, Boldizsar and Graf, Urs and Maspoli, Alessandro and Berger, Wolfgang and Saguner, Ardan M. and Haas, Cordula},\n\tmonth = feb,\n\tyear = {2022},\n\tkeywords = {Alamut, Cardiac counselling, Cardiac diseases, Forensics, Postmortem molecular autopsy, Sudden cardiac death, Sudden unexplained death},\n\tpages = {111240},\n}\n\n

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\n \n\n \n \n \n \n \n \n CAP-ACP Workload Model for Advanced Diagnostics in Precision Medicine.\n \n \n \n \n\n\n \n Park, P. C; Kurek, K. C; DeCoteau, J.; Howlett, C. J; Hawkins, C.; Izevbaye, I.; Carter, M. D; Redpath, M.; Lo, B.; Alex, D.; Yousef, G.; Yip, S.; and Maung, R.\n\n\n \n\n\n\n American Journal of Clinical Pathology,aqac012. February 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"CAP-ACP$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{park_cap-acp_2022,\n\ttitle = {{CAP}-{ACP} {Workload} {Model} for {Advanced} {Diagnostics} in {Precision} {Medicine}},\n\tissn = {0002-9173},\n\turl = {https://doi.org/10.1093/ajcp/aqac012},\n\tdoi = {10.1093/ajcp/aqac012},\n\tabstract = {In precision medicine, where oncologic management is tailored to the individual’s clinical and genetic profiles, advanced diagnostic testing provides prognostic information and guides management in a growing number of malignancies. There is a need to capture the work pathologists perform to meet this demand by providing medically relevant, timely, and accurate testing results. This work includes not only direct patient consults (interpretation of results and issuing reports) but the administrative and medical oversight as well as the research needed to provide the necessary quality assurance, quality control, direction, and framework for the laboratory.An expert panel of Canadian pathologists involved in advanced diagnostics was convened to establish and beta test a model for workload assessment in advanced diagnostics.All aspects of the advanced diagnostics workload were detailed and applied to models based on members’ experience, including medical oversight, administration, and the introduction of new testing and platforms. Models for biomarker testing were developed for simple and complex or multiplexed assays, and a detailed model was developed to assess the workload for next-generation sequencing–based assays.This paper provides the first detailed proposal for capturing an advanced diagnostic workload to enable appropriate pathologist allotment for performing all the steps required to run an advanced diagnostic service.},\n\turldate = {2022-03-10},\n\tjournal = {American Journal of Clinical Pathology},\n\tauthor = {Park, Paul C and Kurek, Kyle C and DeCoteau, John and Howlett, Christopher J and Hawkins, Cynthia and Izevbaye, Iyare and Carter, Michael D and Redpath, Margaret and Lo, Bryan and Alex, Deepu and Yousef, George and Yip, Stephen and Maung, Raymond},\n\tmonth = feb,\n\tyear = {2022},\n\tpages = {aqac012},\n}\n\n

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\n \n\n \n \n \n \n \n \n Two cases with mitochondrial membrane protein-associated neurodegeneration: genetic features and long-term clinical follow-up.\n \n \n \n \n\n\n \n Mercan, S.; Ugur Iseri, S. A.; Yigiter, R.; Akcakaya, N. H.; Saka, E.; and Yapici, Z.\n\n\n \n\n\n\n Neurocase, 0(0): 1–5. February 2022.\n Publisher: Routledge _eprint: https://doi.org/10.1080/13554794.2021.2022702\n\n\n\n
\n\n\n\n \n \n $\"Two$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{mercan_two_2022,\n\ttitle = {Two cases with mitochondrial membrane protein-associated neurodegeneration: genetic features and long-term clinical follow-up},\n\tvolume = {0},\n\tissn = {1355-4794},\n\tshorttitle = {Two cases with mitochondrial membrane protein-associated neurodegeneration},\n\turl = {https://doi.org/10.1080/13554794.2021.2022702},\n\tdoi = {10.1080/13554794.2021.2022702},\n\tabstract = {Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a rare neurological disease with childhood or adult onset. It is a subtype of clinically and genetically heterogeneous group of disorders, collectively known as neurodegeneration with brain iron accumulation . MPAN is generally associated with biallelic pathogenic variants in C19orf12. Herein, we describe genetic and clinical findings of two MPAN cases from Turkey. In the first case, we have identified the relatively common pathogenic variant of C19orf12 in the homozygous state, which causes late-onset MPAN. The second case was homozygous for an essential splice-site variation.},\n\tnumber = {0},\n\turldate = {2022-03-10},\n\tjournal = {Neurocase},\n\tauthor = {Mercan, Sevcan and Ugur Iseri, Sibel Aylin and Yigiter, Remzi and Akcakaya, Nihan Hande and Saka, Esen and Yapici, Zuhal},\n\tmonth = feb,\n\tyear = {2022},\n\tpmid = {35188090},\n\tnote = {Publisher: Routledge\n\\_eprint: https://doi.org/10.1080/13554794.2021.2022702},\n\tkeywords = {C19orf12, Mitochondrial membrane protein-associated neurodegeneration (MPAN), Neurodegeneration with brain iron accumulation (NBIA), SOPHiA DDM, Whole exome sequencing (WES), rare disease},\n\tpages = {1--5},\n}\n\n

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\n \n\n \n \n \n \n \n \n New insights on familial colorectal cancer type X syndrome.\n \n \n \n \n\n\n \n Garcia, F. A. d. O.; de Andrade, E. S.; de Campos Reis Galvão, H.; da Silva Sábato, C.; Campacci, N.; de Paula, A. E.; Evangelista, A. F.; Santana, I. V. V.; Melendez, M. E.; Reis, R. M.; and Palmero, E. I.\n\n\n \n\n\n\n Scientific Reports, 12(1): 2846. February 2022.\n Number: 1 Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"New$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{garcia_new_2022,\n\ttitle = {New insights on familial colorectal cancer type {X} syndrome},\n\tvolume = {12},\n\tcopyright = {2022 The Author(s)},\n\tissn = {2045-2322},\n\turl = {https://www.nature.com/articles/s41598-022-06782-8},\n\tdoi = {10.1038/s41598-022-06782-8},\n\tabstract = {Familial colorectal cancer type X (FCCTX) is a heterogeneous colorectal cancer predisposition syndrome that, although displays a cancer pattern similar to Lynch syndrome, is mismatch repair proficient and does not exhibit microsatellite instability. Besides, its genetic etiology remains to be elucidated. In this study we performed germline exome sequencing of 39 cancer-affected patients from 34 families at risk for FCCTX. Variant classification followed the American College of Medical Genetics and Genomics (ACMG) guidelines. Pathogenic/likely pathogenic variants were identified in 17.65\\% of the families. Rare and potentially pathogenic alterations were identified in known hereditary cancer genes (CHEK2), in putative FCCTX candidate genes (OGG1 and FAN1) and in other cancer-related genes such as ATR, ASXL1, PARK2, SLX4 and TREX1. This study provides novel important clues that can contribute to the understanding of FCCTX genetic basis.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2022-02-22},\n\tjournal = {Scientific Reports},\n\tauthor = {Garcia, Felipe Antonio de Oliveira and de Andrade, Edilene Santos and de Campos Reis Galvão, Henrique and da Silva Sábato, Cristina and Campacci, Natália and de Paula, Andre Escremin and Evangelista, Adriane Feijó and Santana, Iara Viana Vidigal and Melendez, Matias Eliseo and Reis, Rui Manuel and Palmero, Edenir Inez},\n\tmonth = feb,\n\tyear = {2022},\n\tnote = {Number: 1\nPublisher: Nature Publishing Group},\n\tkeywords = {Cancer, Genetics, Molecular biology, Molecular medicine, Oncology, WES, whole exome sequencing},\n\tpages = {2846},\n}\n\n

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\n \n\n \n \n \n \n \n Inborn Errors of Synthesis and Sensitivity to Thyroid Hormone.\n \n \n \n\n\n \n Nicola, J. P.; Wassner, A. J.; and Citterio, C. E.\n\n\n \n\n\n\n Frontiers Media SA, February 2022.\n Google-Books-ID: e2teEAAAQBAJ\n\n\n\n
\n\n\n\n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@book{nicola_inborn_2022,\n\ttitle = {Inborn {Errors} of {Synthesis} and {Sensitivity} to {Thyroid} {Hormone}},\n\tisbn = {978-2-88974-371-1},\n\tlanguage = {en},\n\tpublisher = {Frontiers Media SA},\n\tauthor = {Nicola, Juan Pablo and Wassner, Ari J. and Citterio, Cintia E.},\n\tmonth = feb,\n\tyear = {2022},\n\tnote = {Google-Books-ID: e2teEAAAQBAJ},\n\tkeywords = {CES, Medical / General},\n}\n\n

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\n \n\n \n \n \n \n \n \n Flow Cytometry and Molecular Techniques Could Complement Morphological Detection of Leukemic Infiltration in Ascitic Fluids: A Case Report.\n \n \n \n \n\n\n \n Martínez-Alfonzo, I.; Láinez-González, D.; Solán-Blanco, L.; Franganillo-Suarez, A.; Cornejo, J. I.; Garcia-Lopez, A.; Martín-Herrero, S.; Castaño-Bonilla, T.; Salgado-Sánchez, R.; Arquero-Portero, T.; Cortti-Ferrari, M. J.; Llamas-Sillero, P.; and Alonso-Dominguez, J. M.\n\n\n \n\n\n\n Medicina, 58(2): 264. February 2022.\n Number: 2 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Flow$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{martinez-alfonzo_flow_2022,\n\ttitle = {Flow {Cytometry} and {Molecular} {Techniques} {Could} {Complement} {Morphological} {Detection} of {Leukemic} {Infiltration} in {Ascitic} {Fluids}: {A} {Case} {Report}},\n\tvolume = {58},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {1648-9144},\n\tshorttitle = {Flow {Cytometry} and {Molecular} {Techniques} {Could} {Complement} {Morphological} {Detection} of {Leukemic} {Infiltration} in {Ascitic} {Fluids}},\n\turl = {https://www.mdpi.com/1648-9144/58/2/264},\n\tdoi = {10.3390/medicina58020264},\n\tabstract = {Extramedullary involvement of acute myeloid leukemia (AML) is infrequent, and ascitic infiltration is even more unusual. We present a case of a 48-year-old woman diagnosed with NPM1-mutated AML that debuted with ascites, for which morphological studies of the ascitic fluid did not detect leukemic infiltration, maybe due to technical problems in the sample preparation. Multiparameter flow cytometry (MFC) detected a blast population compatible with AML, and allele-specific PCR detected NPM1-mutated transcripts. Body fluid infiltrations are an infrequent initial manifestation or sign of progression in AML. As far as we know, this is the first reported case of an NPM1-mutated AML that debuted with ascites, and also the first description of the utilization of molecular techniques to detect the leukemic origin of the ascites. This case highlights that, given that allele-specific PCR and MFC increase the sensitivity of morphological studies, these techniques should be routinely applied in the study of any kind of effusion detected in an AML patient.},\n\tlanguage = {en},\n\tnumber = {2},\n\turldate = {2022-02-22},\n\tjournal = {Medicina},\n\tauthor = {Martínez-Alfonzo, Inés and Láinez-González, Daniel and Solán-Blanco, Laura and Franganillo-Suarez, Aida and Cornejo, José I. and Garcia-Lopez, Amanda and Martín-Herrero, Sara and Castaño-Bonilla, Tamara and Salgado-Sánchez, Rocío and Arquero-Portero, Teresa and Cortti-Ferrari, María J. and Llamas-Sillero, Pilar and Alonso-Dominguez, Juan M.},\n\tmonth = feb,\n\tyear = {2022},\n\tnote = {Number: 2\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Acute myeloid leukemia, HCS, NPM1, ascites, nucleophosmin gene (NPM1) mutation},\n\tpages = {264},\n}\n\n

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\n \n\n \n \n \n \n \n \n Importance of multigene panel test in patients with consanguineous marriage and family history of breast cancer.\n \n \n \n \n\n\n \n Ozmen, V.; Caglayan, A. O.; Yararbas, K.; Ordu, C.; Aktepe, F.; Ozmen, T.; Ilgun, A. S.; Soybir, G.; Alco, G.; Tsaousis, G. N.; Papadopoulou, E.; Agiannitopoulos, K.; Pepe, G.; Kampouri, S.; Nasioulas, G.; Sezgin, E.; and Soran, A.\n\n\n \n\n\n\n Oncology Letters, 23(4): 1–9. April 2022.\n Publisher: Spandidos Publications\n\n\n\n
\n\n\n\n \n \n $\"Importance$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{ozmen_importance_2022,\n\ttitle = {Importance of multigene panel test in patients with consanguineous marriage and family history of breast cancer},\n\tvolume = {23},\n\tissn = {1792-1074},\n\turl = {https://www.spandidos-publications.com/10.3892/ol.2022.13238},\n\tdoi = {10.3892/ol.2022.13238},\n\tabstract = {Next‑generation sequencing (NGS) technology is used to evaluate hereditary cancer risks of patients worldwide; however, information concerning the germline multigene mutational spectrum among patients with breast cancer (BC) with consanguineous marriage (CM) is limited. Therefore, this prospective study aimed to determine the molecular characteristics of patients with BC who were tested with multigene hereditary cancer predisposition NGS panel and to show the effect of CM on cancer‑related genes. Patients with BC with or without CM and family history (FH) of BC treated in our breast center were selected according to The National Comprehensive Cancer Network (NCCN) criteria for hereditary BC. In these patients, the analysis of a panel of 33 genes involved in hereditary cancer predisposition was performed after genetic counseling by using NGS. The pathogenic variant (PV) and the variant of uncertain significance (VUS) were found to be 15.8 and 47.4\\%, respectively. PVs were identified in 10/33 genes in 34 patients; 38.2\\% in BRCA1/2 genes; 6, 24, and 14\\% in other high, moderate and low‑risk genes, respectively. The CM rate was 17.7\\% among the 215 patients with BC. The PV rate was 13.2\\% in patients with CM and 16.4\\% in patients without CM (P=0.80). When PV and VUS were evaluated together, the PV+VUS ratio was significantly higher in patients with CM and FH of BC than patients without CM and FH of BC (88.2 vs. 63.3\\%, P=0.045). Analysis of multigene panel provided 9.76\\% additional PVs in moderate/low‑risk genes. The PV rate was similar in patients with BC with or without CM. A high PV+VUS ratio in patients with CM and FH of BC suggests that genes whose importance are unknown are likely to be pathogenic genes later.},\n\tnumber = {4},\n\turldate = {2022-02-22},\n\tjournal = {Oncology Letters},\n\tauthor = {Ozmen, Vahit and Caglayan, Ahmet Okay and Yararbas, Kanay and Ordu, Cetin and Aktepe, Fatma and Ozmen, Tolga and Ilgun, Ahmet Serkan and Soybir, Gursel and Alco, Gul and Tsaousis, Georgios N. and Papadopoulou, Eirini and Agiannitopoulos, Konstantinos and Pepe, Georgia and Kampouri, Stavroula and Nasioulas, George and Sezgin, Efe and Soran, Atilla},\n\tmonth = apr,\n\tyear = {2022},\n\tnote = {Publisher: Spandidos Publications},\n\tkeywords = {HCS},\n\tpages = {1--9},\n}\n\n

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\n \n\n \n \n \n \n \n \n Germline variant testing in serrated polyposis syndrome.\n \n \n \n \n\n\n \n Murphy, A.; Solomons, J.; Risby, P.; Gabriel, J.; Bedenham, T.; Johnson, M.; Atkinson, N.; Bailey, A. A; Bird-Lieberman, E.; Leedham, S. J; East, J. E; and Biswas, S.\n\n\n \n\n\n\n Journal of Gastroenterology and Hepatology, n/a(n/a). February 2022.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/jgh.15791\n\n\n\n
\n\n\n\n \n \n $\"Germline$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{murphy_germline_2022,\n\ttitle = {Germline variant testing in serrated polyposis syndrome},\n\tvolume = {n/a},\n\tissn = {1440-1746},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1111/jgh.15791},\n\tdoi = {10.1111/jgh.15791},\n\tabstract = {Background and Aim Serrated polyposis syndrome (SPS) is now known to be the commonest polyposis syndrome. Previous analyses for germline variants have shown no consistent positive findings. To exclude other polyposis syndromes, 2019 British Society of Gastroenterology (BSG) guidelines advise gene panel testing if the patient is under 50 years, there are multiple affected individuals within a family, or there is dysplasia within any of the polyps. Methods A database of SPS patients was established at the Oxford University Hospitals NHS Foundation Trust. Patients were referred for genetic assessment based on personal and family history and patient preference. The majority were tested for a hereditary colorectal cancer panel including MUTYH, APC, PTEN, SMAD4, BMPR1A, STK11, NTLH1, POLD1, POLE, GREM1 (40-kb duplication), PMS2, and Lynch syndrome mismatch repair genes. Results One hundred and seventy-three patients were diagnosed with SPS based on World Health Organization 2019 criteria between February 2010 and December 2020. The mean age of diagnosis was 54.2 ± 16.8 years. Seventy-three patients underwent genetic testing and 15/73 (20.5\\%) were found to have germline variants, of which 7/73 (9.6\\%) had a pathogenic variant (MUTYH n = 2, SMAD4 n = 1, CHEK2 n = 2, POLD1 n = 1, and RNF43 n = 1). Only 60\\% (9/15) of these patients would have been recommended for gene panel testing according to current BSG guidelines. Conclusions A total of 20.5\\% of SPS patients tested were affected by heterozygous germline variants, including previously unreported associations with CHEK2 and POLD1. This led to a change in management in seven patients (9.6\\%). Current recommendations may miss SPS associated with germline variants, which is more common than previously anticipated.},\n\tlanguage = {en},\n\tnumber = {n/a},\n\turldate = {2022-02-22},\n\tjournal = {Journal of Gastroenterology and Hepatology},\n\tauthor = {Murphy, Aisling and Solomons, Joyce and Risby, Peter and Gabriel, Jessica and Bedenham, Tina and Johnson, Michael and Atkinson, Nathan and Bailey, Adam A and Bird-Lieberman, Elizabeth and Leedham, Simon J and East, James E and Biswas, Sujata},\n\tmonth = feb,\n\tyear = {2022},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/jgh.15791},\n\tkeywords = {HCS, colon, genetics, polyposis},\n}\n\n

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\n \n\n \n \n \n \n \n \n Consistency of variant interpretations among bioinformaticians and clinical geneticists in hereditary cancer panels.\n \n \n \n \n\n\n \n Agaoglu, N. B.; Unal, B.; Akgun Dogan, O.; Kanev, M. O.; Zolfagharian, P.; Ozemri Sag, S.; Temel, S. G.; and Doganay, L.\n\n\n \n\n\n\n European Journal of Human Genetics,1–6. February 2022.\n Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"Consistency$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 8 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{agaoglu_consistency_2022,\n\ttitle = {Consistency of variant interpretations among bioinformaticians and clinical geneticists in hereditary cancer panels},\n\tcopyright = {2022 The Author(s), under exclusive licence to European Society of Human Genetics},\n\tissn = {1476-5438},\n\turl = {https://www.nature.com/articles/s41431-022-01060-7},\n\tdoi = {10.1038/s41431-022-01060-7},\n\tabstract = {Next-generation sequencing (NGS) is used increasingly in hereditary cancer patients' (HCP) management. While enabling evaluation of multiple genes simultaneously, the technology brings to light the dilemma of variant interpretation. Here, we aimed to reveal the underlying reasons for the discrepancy in the evidence titles used during variant classification according to ACMG guidelines by two different bioinformatic specialists (BIs) and two different clinical geneticists (CGs). We evaluated final reports of 1920 cancer patients and 189 different variants from 285 HCP were enrolled to the study. A total of 173 of these variants were classified as pathogenic (n = 132) and likely pathogenic (n = 41) by the BI and an additional 16 variants, that were classified as VUS by at least one interpreter and their classification would change the clinical management, were compared for their evidence titles between different specialists. The attributed evidence titles and the final classification of the variants among BIs and CGs were compared. The discrepancy between P/LP final reports was 22.5\\%. The discordance between CGs was 30\\% whereas the discordance between two BIs was almost 75\\%. The use of PVS1, PS3, PP3, PP5, PM1, PM2, BP1, BP4 criteria markedly varied from one expert to another. This difference was particularly noticeable in PP3, PP5, and PM1 evidence and mostly in the variants affecting splice sites like BRCA1(NM\\_007294.4) c.4096 + 1 G {\\textgreater} A and CHEK2(NM\\_007194.4) c.592 + 3 A {\\textgreater} T. With recent advancements in precision medicine, the importance of variant interpretations is emerging. Our study shows that variant interpretation is subjective process that is in need of concrete definitions for accurate and standard interpretation.},\n\tlanguage = {en},\n\turldate = {2022-02-22},\n\tjournal = {European Journal of Human Genetics},\n\tauthor = {Agaoglu, Nihat Bugra and Unal, Busra and Akgun Dogan, Ozlem and Kanev, Martin Orlinov and Zolfagharian, Payam and Ozemri Sag, Sebnem and Temel, Sehime Gulsun and Doganay, Levent},\n\tmonth = feb,\n\tyear = {2022},\n\tnote = {Publisher: Nature Publishing Group},\n\tkeywords = {Cancer genetics, Genetics research, HCS, Sequence annotation},\n\tpages = {1--6},\n}\n\n

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\n \n\n \n \n \n \n \n \n Development of a non-viral delivery nanoplatform for genomic therapy based on iron oxide nanoparticles and recombinant Cas9 for potential use in genetic heterozygous orphan diseases.\n \n \n \n \n\n\n \n Ellis-Aguilar, L. D.\n\n\n \n\n\n\n . January 2022.\n Accepted: 2022-02-01T21:48:42Z Publisher: Universidad de los Andes\n\n\n\n
\n\n\n\n \n \n $\"Development$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{ellis-aguilar_development_2022,\n\ttitle = {Development of a non-viral delivery nanoplatform for genomic therapy based on iron oxide nanoparticles and recombinant {Cas9} for potential use in genetic heterozygous orphan diseases},\n\tcopyright = {Al consultar y hacer uso de este recurso, está aceptando las condiciones de uso establecidas por los autores.},\n\turl = {https://repositorio.uniandes.edu.co/handle/1992/54468},\n\tabstract = {Since it was first described, the CRISPR/Cas9 technology has opened new possibilities in the molecular biology fields. CRISPR/Cas9 has become one of the favorite tools for researchers from cell culture improvement to design of therapies for rare diseases. However, its clinical application has been hindered by the dearth of safe and efficient delivery systems. Here, we develop and characterized a magnetite-based nanoplatform to potentially deliver, both recombinant Cas9 and single guide RNA (sgRNA) targeting a pathogenic COL3A1 mutation in a cell culture model of hereditary Thoracic Aortic Aneurism. Specifically, we designed and synthesized several sgRNAs to test their activity through an allele specific DNA digestion assay. For this, we amplified the affected region using genomic DNA from a patient carrying the mutation and evaluated the cleavage efficiency of different Cas9-sgRNA ribonucleoproteins. Once the optimal conditions were obtained, we carried out DiGenome-Seq analysis to identify potential off-target effects. In parallel, we synthesized Magnetite Nanoparticles (MNPs), functionalized the particles by adding a polymer spacer (polyethylene glycol PEG) and conjugated the cell-penetrating peptide (CPP) Buforin II (BUFII) for membrane translocation alongside recombinant Cas9. We successfully characterized the MNP-PEG-BUFII-Cas9 conjugates by transmission electron microscopy (TEM) and dynamic light scattering (DLS), finding an average particle size of 15 nm and a hydrodynamic diameter from 120 to 250 nm. Fourier transform infrared spectroscopy (FTIR) lead us to corroborate correct functionalization in each step and find N-H stretch peaks at 3180 cm ¹ and 3500 cm ¹ which corresponded to the Cas9. And thermogravimetric analysis (TGA) displayed rising weight losses (6.97\\%, 7.77\\%, 10.41\\%) in each step of the synthesis. We also conducted a biocompatibility battery test that includes lactate dehydrogenase (LDH) cytotoxicity assay, platelet aggregation, hemolytic activity, and the Ames test for mutagenicity (Salmonella Tiphimurium TA98 strain). We demonstrated in vitro biocompatibility and highlight a platelet aggregation behavior (p {\\textgreater} 0.001) of MNP-PEG-BUFII-Cas9. Finally, we performed a proof-of-principle of our MNP-PEG-BUFII-Cas9 nanoplatform, evaluating cell (HDFa and HaCat) internalization and endosomal escape of the MNP-PEG-BUFII-Cas9 without the sgRNA by confocal microscope image analysis. Overall, here we demonstrate the efficacy of MNP-PEG-BUFII-Cas9 nanoplatform as safe and promising non-viral delivery vehicles for CRISPR/Cas9 localized gene editing attempting to treat heterozygous mutations.},\n\tlanguage = {eng},\n\turldate = {2022-02-11},\n\tauthor = {Ellis-Aguilar, Laura Daniela},\n\tmonth = jan,\n\tyear = {2022},\n\tnote = {Accepted: 2022-02-01T21:48:42Z\nPublisher: Universidad de los Andes},\n\tkeywords = {SOPHiA DDM},\n}\n\n

\n\n\n

\n Since it was first described, the CRISPR/Cas9 technology has opened new possibilities in the molecular biology fields. CRISPR/Cas9 has become one of the favorite tools for researchers from cell culture improvement to design of therapies for rare diseases. However, its clinical application has been hindered by the dearth of safe and efficient delivery systems. Here, we develop and characterized a magnetite-based nanoplatform to potentially deliver, both recombinant Cas9 and single guide RNA (sgRNA) targeting a pathogenic COL3A1 mutation in a cell culture model of hereditary Thoracic Aortic Aneurism. Specifically, we designed and synthesized several sgRNAs to test their activity through an allele specific DNA digestion assay. For this, we amplified the affected region using genomic DNA from a patient carrying the mutation and evaluated the cleavage efficiency of different Cas9-sgRNA ribonucleoproteins. Once the optimal conditions were obtained, we carried out DiGenome-Seq analysis to identify potential off-target effects. In parallel, we synthesized Magnetite Nanoparticles (MNPs), functionalized the particles by adding a polymer spacer (polyethylene glycol PEG) and conjugated the cell-penetrating peptide (CPP) Buforin II (BUFII) for membrane translocation alongside recombinant Cas9. We successfully characterized the MNP-PEG-BUFII-Cas9 conjugates by transmission electron microscopy (TEM) and dynamic light scattering (DLS), finding an average particle size of 15 nm and a hydrodynamic diameter from 120 to 250 nm. Fourier transform infrared spectroscopy (FTIR) lead us to corroborate correct functionalization in each step and find N-H stretch peaks at 3180 cm ¹ and 3500 cm ¹ which corresponded to the Cas9. And thermogravimetric analysis (TGA) displayed rising weight losses (6.97%, 7.77%, 10.41%) in each step of the synthesis. We also conducted a biocompatibility battery test that includes lactate dehydrogenase (LDH) cytotoxicity assay, platelet aggregation, hemolytic activity, and the Ames test for mutagenicity (Salmonella Tiphimurium TA98 strain). We demonstrated in vitro biocompatibility and highlight a platelet aggregation behavior (p \\textgreater 0.001) of MNP-PEG-BUFII-Cas9. Finally, we performed a proof-of-principle of our MNP-PEG-BUFII-Cas9 nanoplatform, evaluating cell (HDFa and HaCat) internalization and endosomal escape of the MNP-PEG-BUFII-Cas9 without the sgRNA by confocal microscope image analysis. Overall, here we demonstrate the efficacy of MNP-PEG-BUFII-Cas9 nanoplatform as safe and promising non-viral delivery vehicles for CRISPR/Cas9 localized gene editing attempting to treat heterozygous mutations.\n

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\n \n\n \n \n \n \n \n \n Adult-onset CblC deficiency: a challenging diagnosis involving different adult clinical specialists.\n \n \n \n \n\n\n \n Kalantari, S.; Brezzi, B.; Bracciamà, V.; Barreca, A.; Nozza, P.; Vaisitti, T.; Amoroso, A.; Deaglio, S.; Manganaro, M.; Porta, F.; and Spada, M.\n\n\n \n\n\n\n Orphanet Journal of Rare Diseases, 17(1): 33. February 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Adult-onset$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{kalantari_adult-onset_2022,\n\ttitle = {Adult-onset {CblC} deficiency: a challenging diagnosis involving different adult clinical specialists},\n\tvolume = {17},\n\tissn = {1750-1172},\n\tshorttitle = {Adult-onset {CblC} deficiency},\n\turl = {https://doi.org/10.1186/s13023-022-02179-y},\n\tdoi = {10.1186/s13023-022-02179-y},\n\tabstract = {Methylmalonic aciduria and homocystinuria, CblC type (OMIM \\#277400) is the most common disorder of cobalamin intracellular metabolism, an autosomal recessive disease, whose biochemical hallmarks are hyperhomocysteinemia, methylmalonic aciduria and low plasma methionine. Despite being a well-recognized disease for pediatricians, there is scarce awareness of its adult presentation. A thorough analysis and discussion of cobalamin C defect presentation in adult patients has never been extensively performed. This article reviews the published data and adds a new case of the latest onset of symptoms ever described for the disease.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2022-02-11},\n\tjournal = {Orphanet Journal of Rare Diseases},\n\tauthor = {Kalantari, Silvia and Brezzi, Brigida and Bracciamà, Valeria and Barreca, Antonella and Nozza, Paolo and Vaisitti, Tiziana and Amoroso, Antonio and Deaglio, Silvia and Manganaro, Marco and Porta, Francesco and Spada, Marco},\n\tmonth = feb,\n\tyear = {2022},\n\tkeywords = {Alamut},\n\tpages = {33},\n}\n\n

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\n \n\n \n \n \n \n \n \n An evaluation of pipelines for DNA variant detection can guide a reanalysis protocol to increase the diagnostic ratio of genetic diseases.\n \n \n \n \n\n\n \n Romero, R.; de la Fuente, L.; Del Pozo-Valero, M.; Riveiro-Álvarez, R.; Trujillo-Tiebas, M. J.; Martín-Mérida, I.; Ávila-Fernández, A.; Iancu, I.; Perea-Romero, I.; Núñez-Moreno, G.; Damián, A.; Rodilla, C.; Almoguera, B.; Cortón, M.; Ayuso, C.; and Mínguez, P.\n\n\n \n\n\n\n npj Genomic Medicine, 7(1): 1–10. January 2022.\n Number: 1 Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"An$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{romero_evaluation_2022,\n\ttitle = {An evaluation of pipelines for {DNA} variant detection can guide a reanalysis protocol to increase the diagnostic ratio of genetic diseases},\n\tvolume = {7},\n\tcopyright = {2022 The Author(s)},\n\tissn = {2056-7944},\n\turl = {https://www.nature.com/articles/s41525-021-00278-6},\n\tdoi = {10.1038/s41525-021-00278-6},\n\tabstract = {Clinical exome (CE) sequencing has become a first-tier diagnostic test for hereditary diseases; however, its diagnostic rate is around 30–50\\%. In this study, we aimed to increase the diagnostic yield of CE using a custom reanalysis algorithm. Sequencing data were available for three cohorts using two commercial protocols applied as part of the diagnostic process. Using these cohorts, we compared the performance of general and clinically relevant variant calling and the efficacy of an in-house bioinformatic protocol (FJD-pipeline) in detecting causal variants as compared to commercial protocols. On the whole, the FJD-pipeline detected 99.74\\% of the causal variants identified by the commercial protocol in previously solved cases. In the unsolved cases, FJD-pipeline detects more INDELs and non-exonic variants, and is able to increase the diagnostic yield in 2.5\\% and 3.2\\% in the re-analysis of 78 cancer and 62 cardiovascular cases. These results were considered to design a reanalysis, filtering and prioritization algorithm that was tested by reassessing 68 inconclusive cases of monoallelic autosomal recessive retinal dystrophies increasing the diagnosis by 4.4\\%. In conclusion, a guided NGS reanalysis of unsolved cases increases the diagnostic yield in genetic disorders, making it a useful diagnostic tool in medical genetics.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2022-02-11},\n\tjournal = {npj Genomic Medicine},\n\tauthor = {Romero, Raquel and de la Fuente, Lorena and Del Pozo-Valero, Marta and Riveiro-Álvarez, Rosa and Trujillo-Tiebas, María José and Martín-Mérida, Inmaculada and Ávila-Fernández, Almudena and Iancu, Ionut-Florin and Perea-Romero, Irene and Núñez-Moreno, Gonzalo and Damián, Alejandra and Rodilla, Cristina and Almoguera, Berta and Cortón, Marta and Ayuso, Carmen and Mínguez, Pablo},\n\tmonth = jan,\n\tyear = {2022},\n\tnote = {Number: 1\nPublisher: Nature Publishing Group},\n\tkeywords = {Genetics research, Genome informatics, HCS, TSC, TruSight},\n\tpages = {1--10},\n}\n\n

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\n \n\n \n \n \n \n \n \n Clonal evolution in patients developing therapy-related myeloid neoplasms following autologous stem cell transplantation.\n \n \n \n \n\n\n \n Soerensen, J. F.; Aggerholm, A.; Rosenberg, C. A.; Bill, M.; Kerndrup, G. B.; Ebbesen, L. H.; Hansen, M. H.; Roug, A. S.; and Ludvigsen, M.\n\n\n \n\n\n\n Bone Marrow Transplantation,1–6. January 2022.\n Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"Clonal$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{soerensen_clonal_2022,\n\ttitle = {Clonal evolution in patients developing therapy-related myeloid neoplasms following autologous stem cell transplantation},\n\tcopyright = {2022 The Author(s), under exclusive licence to Springer Nature Limited},\n\tissn = {1476-5365},\n\turl = {https://www.nature.com/articles/s41409-022-01567-z},\n\tdoi = {10.1038/s41409-022-01567-z},\n\tabstract = {Clonal hematopoiesis (CH) denotes somatic mutations in genes related to myeloid neoplasms present at any variant allele frequency (VAF). Clonal hematopoiesis is associated with increasing age and with a factor 6 increase in the risk of developing therapy-related myeloid neoplasms (tMNs) following autologous stem cell transplantation (ASCT). However, the impact of specific mutations on progression from CH to tMN has yet to be unraveled, and it remains unclear whether mutations directly impact or even drive the development of tMN. We performed deep sequencing in longitudinal samples from a cohort of 12 patients with either multiple myeloma or lymphoma who developed tMN following ASCT. Nine patients had one or more mutations that could be tracked longitudinally. Seven patients had clonal expansion from time of ASCT to diagnosis of tMN. Of these, six patients had CH at VAF {\\textless} 2\\% at baseline. The median VAF of non-DNMT3A clones increased from 1\\% (IQR 0.7\\%–10.0\\%) at time of ASCT to 37\\% (IQR 17\\%–47\\%) at tMN diagnosis (P = 0.002), while DNMT3A clones showed quiescent trajectories (P = 0.625). Our data provide evidence to support the hypothesis that the development of tMN following ASCT is likely instigated by CH present at VAFs as low as 0.5\\%, detectable years before tMN onset.},\n\tlanguage = {en},\n\turldate = {2022-02-11},\n\tjournal = {Bone Marrow Transplantation},\n\tauthor = {Soerensen, Johannes Frasez and Aggerholm, Anni and Rosenberg, Carina Agerbo and Bill, Marie and Kerndrup, Gitte Birk and Ebbesen, Lene Hyldahl and Hansen, Marcus Høy and Roug, Anne Stidsholt and Ludvigsen, Maja},\n\tmonth = jan,\n\tyear = {2022},\n\tnote = {Publisher: Nature Publishing Group},\n\tkeywords = {Genetics research, MYS, Oncogenesis, Risk factors, Translational research},\n\tpages = {1--6},\n}\n\n

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\n \n\n \n \n \n \n \n \n New Perspectives on the Recurrent BRCA Mutations and Clinical Variability.\n \n \n \n \n\n\n \n Sahin, I.; Saat, H.; and Aksoy, S.\n\n\n \n\n\n\n International Journal of Hematology and Oncology, 32(1): 044–049. January 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"New$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{sahin_new_2022,\n\ttitle = {New {Perspectives} on the {Recurrent} {BRCA} {Mutations} and {Clinical} {Variability}},\n\tvolume = {32},\n\tissn = {1306 - 133X},\n\turl = {http://uhod.org/summary.php3?id=899},\n\tabstract = {UHOD Impact factor 2.323, UHOD covers areas of interest relating to radiation oncology, medical ongology, surgical oncology, and hematology.},\n\tlanguage = {English},\n\tnumber = {1},\n\turldate = {2022-01-25},\n\tjournal = {International Journal of Hematology and Oncology},\n\tauthor = {Sahin, Ibrahim and Saat, Hanife and Aksoy, Sercan},\n\tmonth = jan,\n\tyear = {2022},\n\tkeywords = {HCS},\n\tpages = {044--049},\n}\n\n

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\n \n\n \n \n \n \n \n \n First identification of the new SARS-CoV-2 Omicron variant (B.1.1.529) in Italy.\n \n \n \n \n\n\n \n Micheli, V.; Bracchitta, F.; Rizzo, A.; Mancon, A.; Mileto, D.; Lombardi, A.; Stefanelli, P.; and Gismondo, M. R.\n\n\n \n\n\n\n Clinical Infectious Diseases,ciab1044. January 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"First$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{micheli_first_2022,\n\ttitle = {First identification of the new {SARS}-{CoV}-2 {Omicron} variant ({B}.1.1.529) in {Italy}},\n\tissn = {1058-4838},\n\turl = {https://doi.org/10.1093/cid/ciab1044},\n\tdoi = {10.1093/cid/ciab1044},\n\tabstract = {We identified the first case in Italy of SARS-CoV-2 B.1.1.529 variant by whole genome sequencing in an Italian subject travelling from Mozambique. Specific mutation profiles deserve further investigations to clarify potential effects on vaccination efficacy.This case highlights the crucial role of rapid and continuous surveillance of SARS-CoV-2 variant circulation.},\n\turldate = {2022-01-25},\n\tjournal = {Clinical Infectious Diseases},\n\tauthor = {Micheli, Valeria and Bracchitta, Fiorenza and Rizzo, Alberto and Mancon, Alessandro and Mileto, Davide and Lombardi, Alessandra and Stefanelli, Paola and Gismondo, Maria Rita},\n\tmonth = jan,\n\tyear = {2022},\n\tkeywords = {SOPHiA DDM},\n\tpages = {ciab1044},\n}\n\n

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\n \n\n \n \n \n \n \n \n Beyond BRCA1/2: Homologous Recombination Repair Genetic Profile in a Large Cohort of Apulian Ovarian Cancers.\n \n \n \n \n\n\n \n Turchiano, A.; Loconte, D. C.; De Nola, R.; Arezzo, F.; Chiarello, G.; Pantaleo, A.; Iacoviello, M.; Bagnulo, R.; De Luisi, A.; Perrelli, S.; Martino, S.; Ranieri, C.; Garganese, A.; Stella, A.; Forleo, C.; Loizzi, V.; Marinaccio, M.; Cicinelli, E.; Cormio, G.; and Resta, N.\n\n\n \n\n\n\n Cancers, 14(2): 365. January 2022.\n Number: 2 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Beyond$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{turchiano_beyond_2022,\n\ttitle = {Beyond {BRCA1}/2: {Homologous} {Recombination} {Repair} {Genetic} {Profile} in a {Large} {Cohort} of {Apulian} {Ovarian} {Cancers}},\n\tvolume = {14},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tshorttitle = {Beyond {BRCA1}/2},\n\turl = {https://www.mdpi.com/2072-6694/14/2/365},\n\tdoi = {10.3390/cancers14020365},\n\tabstract = {Background: Pathogenic variants in homologous recombination repair (HRR) genes other than BRCA1/2 have been associated with a high risk of ovarian cancer (OC). In current clinical practice, genetic testing is generally limited to BRCA1/2. Herein, we investigated the mutational status of both BRCA1/2 and 5 HRR genes in 69 unselected OC, evaluating the advantage of multigene panel testing in everyday clinical practice. Methods: We analyzed 69 epithelial OC samples using an NGS custom multigene panel of the 5 HRR pathways genes, beyond the genetic screening routine of BRCA1/2 testing. Results: Overall, 19 pathogenic variants (27.5\\%) were detected. The majority (21.7\\%) of patients displayed a deleterious mutation in BRCA1/2, whereas 5.8\\% harbored a pathogenic variant in one of the HRR genes. Additionally, there were 14 (20.3\\%) uncertain significant variants (VUS). The assessment of germline mutational status showed that a small number of variants (five) were not detected in the corresponding blood sample. Notably, we detected one BRIP1 and four BRCA1/2 deleterious variants in the low-grade serous and endometrioid histology OC, respectively. Conclusion: We demonstrate that using a multigene panel beyond BRCA1/2 improves the diagnostic yield in OC testing, and it could produce clinically relevant results.},\n\tlanguage = {en},\n\tnumber = {2},\n\turldate = {2022-01-20},\n\tjournal = {Cancers},\n\tauthor = {Turchiano, Antonella and Loconte, Daria Carmela and De Nola, Rosalba and Arezzo, Francesca and Chiarello, Giulia and Pantaleo, Antonino and Iacoviello, Matteo and Bagnulo, Rosanna and De Luisi, Annunziata and Perrelli, Sonia and Martino, Stefania and Ranieri, Carlotta and Garganese, Antonella and Stella, Alessandro and Forleo, Cinzia and Loizzi, Vera and Marinaccio, Marco and Cicinelli, Ettore and Cormio, Gennaro and Resta, Nicoletta},\n\tmonth = jan,\n\tyear = {2022},\n\tnote = {Number: 2\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Alamut, BRCA1/2, HHR genes, PARPi, ovarian cancer, target resequencing},\n\tpages = {365},\n}\n\n

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\n \n\n \n \n \n \n \n \n Steroid hormone profiles and molecular diagnostic tools in pediatric patients with non-CAH primary adrenal insufficiency.\n \n \n \n \n\n\n \n Seven Menevse, T.; Kendir Demirkol, Y.; Gurpinar Tosun, B.; Bayramoglu, E.; Yildiz, M.; Acar, S.; Erisen Karaca, S.; Orbak, Z.; Onder, A.; Sobu, E.; Anık, A.; Atay, Z.; Bugrul, F.; Bulus, A. D.; Demir, K.; Dogan, D.; Emeksiz, H. C.; Kirmizibekmez, H.; Ozcan Murat, N.; Yaman, A.; Turan, S.; Bereket, A.; and Guran, T.\n\n\n \n\n\n\n The Journal of Clinical Endocrinology & Metabolism,dgac016. January 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Steroid$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{seven_menevse_steroid_2022,\n\ttitle = {Steroid hormone profiles and molecular diagnostic tools in pediatric patients with non-{CAH} primary adrenal insufficiency},\n\tissn = {0021-972X},\n\turl = {https://doi.org/10.1210/clinem/dgac016},\n\tdoi = {10.1210/clinem/dgac016},\n\tabstract = {There is a significant challenge of attributing specific diagnoses to patients with primary adrenal insufficiency of unknown etiology other than congenital adrenal hyperplasia (non-CAH PAI). Specific diagnoses per se may guide personalized treatment or may illuminate pathophysiology.Investigation of the efficacy of steroid hormone profiles and high-throughput sequencing methods in establishing the etiology in non-CAH PAI of unknown origin.Paediatric patients with non-CAH PAI whose etiology could not be established by clinical and biochemical characteristics were enrolled. Genetic analysis was performed using targetedgene panel sequencing (TPS) and whole-exome sequencing (WES). Plasma adrenal steroids were quantified by liquid chromatography-mass spectrometry and compared to that of controls.Eighteen pediatric endocrinology clinics.Forty-one patients (17 females, median age: 3 months, range: 0-8 years) with non-CAH PAI of unknown etiology.A genetic diagnosis was obtained in 29 (70.7\\%) patients by TPS. Further molecular diagnosis could not be achieved by WES. Compared to healthy control group, patients showed lower steroid concentrations, most significantly in cortisone, cortisol, and corticosterone (p\\&lt;0.0001, area under the ROC curve: 0.96, 0.88, 0.87, respectively). Plasma cortisol\\&lt;4 ng/mL, cortisone\\&lt;11 ng/mL, and corticosterone\\&lt;0.11 ng/mL had \\&gt;95\\% specificity to ensure the diagnosis of non-CAH PAI of unknown etiology.Steroid hormone profiles are highly sensitive for the diagnosis of non-CAH PAI of unknown etiology, while they are unlikely to point out a specific molecular diagnosis. TPS is an optimal approach in the molecular diagnosis of these patients with high efficacy, while little additional benefit is expected from WES.},\n\turldate = {2022-01-20},\n\tjournal = {The Journal of Clinical Endocrinology \\& Metabolism},\n\tauthor = {Seven Menevse, Tuba and Kendir Demirkol, Yasemin and Gurpinar Tosun, Busra and Bayramoglu, Elvan and Yildiz, Melek and Acar, Sezer and Erisen Karaca, Seda and Orbak, Zerrin and Onder, Asan and Sobu, Elif and Anık, Ahmet and Atay, Zeynep and Bugrul, Fuat and Bulus, Ayse Derya and Demir, Korcan and Dogan, Durmus and Emeksiz, Hamdi Cihan and Kirmizibekmez, Heves and Ozcan Murat, Nurhan and Yaman, Akan and Turan, Serap and Bereket, Abdullah and Guran, Tulay},\n\tmonth = jan,\n\tyear = {2022},\n\tkeywords = {Clinical Exome},\n\tpages = {dgac016},\n}\n\n

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\n \n\n \n \n \n \n \n \n Identification and Characterization of an Exonic Duplication in PALB2 in a Man with Synchronous Breast and Prostate Cancer.\n \n \n \n \n\n\n \n Bouras, A.; Lafaye, C.; Leone, M.; Kherraf, Z.; Martin-Denavit, T.; Fert-Ferrer, S.; Calender, A.; and Boutry-Kryza, N.\n\n\n \n\n\n\n International Journal of Molecular Sciences, 23(2): 667. January 2022.\n Number: 2 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Identification$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{bouras_identification_2022,\n\ttitle = {Identification and {Characterization} of an {Exonic} {Duplication} in {PALB2} in a {Man} with {Synchronous} {Breast} and {Prostate} {Cancer}},\n\tvolume = {23},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\turl = {https://www.mdpi.com/1422-0067/23/2/667},\n\tdoi = {10.3390/ijms23020667},\n\tabstract = {PALB2 (partner and localizer of BRCA2), as indicated by its name, is a BRCA2-interacting protein that plays an important role in homologous recombination (HR) and DNA double-strand break (DSB) repair. While pathogenic variants of PALB2 have been well proven to confer an increased risk of breast cancer, data on its involvement in prostate cancer (PrC) have not been clearly demonstrated. We investigated, using targeted next generation sequencing (NGS), a 59-year-old Caucasian man who developed synchronous breast and prostate cancers. This genetic investigation allowed to identify an intragenic germline heterozygous duplication in PALB2, implicating intronic repetitive sequences spanning exon 11. This variant was confirmed by multiplex ligation probe amplification (MLPA), and genomic breakpoints have been identified and characterized at the nucleotide level (c.3114-811\\_3202-1756dup) using an approach based on walking PCR, long range PCR, and Sanger sequencing. RT-PCR using mRNA extracted from lymphocytes and followed by Sanger sequencing revealed a tandem duplication r.3114\\_3201dup; p.(Gly1068Glufs * 14). This duplication results in the synthesis of a truncated, and most-likely, non-functional protein. These findings expand the phenotypic spectrum of PALB2 variants and may improve the yield of genetic diagnoses in this field.},\n\tlanguage = {en},\n\tnumber = {2},\n\turldate = {2022-01-20},\n\tjournal = {International Journal of Molecular Sciences},\n\tauthor = {Bouras, Ahmed and Lafaye, Cyril and Leone, Melanie and Kherraf, Zine-Eddine and Martin-Denavit, Tanguy and Fert-Ferrer, Sandra and Calender, Alain and Boutry-Kryza, Nadia},\n\tmonth = jan,\n\tyear = {2022},\n\tnote = {Number: 2\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {CE-IVD, HCS, PALB2, breast cancer, exon duplication, prostate cancer},\n\tpages = {667},\n}\n\n

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\n \n\n \n \n \n \n \n \n SARS-CoV-2 detection in primary thyroid sarcoma: coincidence or interaction?.\n \n \n \n \n\n\n \n Tanda, M. L.; Ippolito, S.; Gallo, D.; Baj, A.; Novazzi, F.; Genoni, A.; Annoni, M.; Mancini, N.; Clementi, N.; Finzi, G.; Piantanida, E.; Premoli, P.; Lai, A.; Dalla Gasperina, D.; Maggi, F.; and Uccella, S.\n\n\n \n\n\n\n Journal of Endocrinological Investigation. January 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"SARS-CoV-2$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{tanda_sars-cov-2_2022,\n\ttitle = {{SARS}-{CoV}-2 detection in primary thyroid sarcoma: coincidence or interaction?},\n\tissn = {1720-8386},\n\tshorttitle = {{SARS}-{CoV}-2 detection in primary thyroid sarcoma},\n\turl = {https://doi.org/10.1007/s40618-021-01722-1},\n\tdoi = {10.1007/s40618-021-01722-1},\n\tabstract = {Thyroid dysfunctions associated with SARS-CoV-2 are emerging in scientific literature. During the second COVID-19 epidemic spread, we evaluated a patient with the suspect of subacute thyroiditis.},\n\tlanguage = {en},\n\turldate = {2022-01-20},\n\tjournal = {Journal of Endocrinological Investigation},\n\tauthor = {Tanda, M. L. and Ippolito, S. and Gallo, D. and Baj, A. and Novazzi, F. and Genoni, A. and Annoni, M. and Mancini, N. and Clementi, N. and Finzi, G. and Piantanida, E. and Premoli, P. and Lai, A. and Dalla Gasperina, D. and Maggi, F. and Uccella, S.},\n\tmonth = jan,\n\tyear = {2022},\n\tkeywords = {SOPHiA DDM},\n}\n\n

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\n \n 2021\n \n \n (134)\n \n \n

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\n \n\n \n \n \n \n \n \n Genome sequence diversity of SARS-CoV-2 obtained from clinical samples in Uzbekistan.\n \n \n \n \n\n\n \n Abdullaev, A.; Abdurakhimov, A.; Mirakbarova, Z.; Ibragimova, S.; Tsoy, V.; Nuriddinov, S.; Dalimova, D.; Turdikulova, S.; and Abdurakhmonov, I.\n\n\n \n\n\n\n PLOS ONE, 17(6): e0270314. June 2021.\n Publisher: Public Library of Science\n\n\n\n
\n\n\n\n \n \n $\"Genome$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{abdullaev_genome_2021,\n\ttitle = {Genome sequence diversity of {SARS}-{CoV}-2 obtained from clinical samples in {Uzbekistan}},\n\tvolume = {17},\n\tissn = {1932-6203},\n\turl = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0270314},\n\tdoi = {10.1371/journal.pone.0270314},\n\tabstract = {Tracking temporal and spatial genomic changes and evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are among the most urgent research topics worldwide, which help to elucidate the coronavirus disease 2019 (COVID-19) pathogenesis and the effect of deleterious variants. Our current study concentrates genetic diversity of SARS-CoV-2 variants in Uzbekistan and their associations with COVID-19 severity. Thirty-nine whole genome sequences (WGS) of SARS-CoV-2 isolated from PCR-positive patients from Tashkent, Uzbekistan for the period of July-August 2021, were generated and further subjected to further genomic analysis. Genome-wide annotations of clinical isolates from our study have revealed a total of 223 nucleotide-level variations including SNPs and 34 deletions at different positions throughout the entire genome of SARS-CoV-2. These changes included two novel mutations at the Nonstructural protein (Nsp) 13: A85P and Nsp12: Y479N, which were unreported previously. There were two groups of co-occurred substitution patterns: the missense mutations in the Spike (S): D614G, Open Reading Frame (ORF) 1b: P314L, Nsp3: F924, 5`UTR:C241T; Nsp3:P2046L and Nsp3:P2287S, and the synonymous mutations in the Nsp4:D2907 (C8986T), Nsp6:T3646A and Nsp14:A1918V regions, respectively. The “Nextstrain” clustered the largest number of SARS-CoV-2 strains into the Delta clade (n = 32; 82\\%), followed by two Alpha-originated (n = 4; 10,3\\%) and 20A (n = 3; 7,7\\%) clades. Geographically the Delta clade sample sequences were grouped into several clusters with the SARS-CoV genotypes from Russia, Denmark, USA, Egypt and Bangladesh. Phylogenetically, the Delta isolates in our study belong to the two main subclades 21A (56\\%) and 21J (44\\%). We found that females were more affected by 21A, whereas males by 21J variant (χ2 = 4.57; p ≤ 0.05, n = 32). The amino acid substitution ORF7a:P45L in the Delta isolates found to be significantly associated with disease severity. In conclusion, this study evidenced that Identified novel substitutions Nsp13: A85P and Nsp12: Y479N, have a destabilizing effect, while missense substitution ORF7a: P45L significantly associated with disease severity.},\n\tlanguage = {en},\n\tnumber = {6},\n\turldate = {2022-07-28},\n\tjournal = {PLOS ONE},\n\tauthor = {Abdullaev, Alisher and Abdurakhimov, Abrorjon and Mirakbarova, Zebinisa and Ibragimova, Shakhnoza and Tsoy, Vladimir and Nuriddinov, Sharofiddin and Dalimova, Dilbar and Turdikulova, Shahlo and Abdurakhmonov, Ibrokhim},\n\tmonth = jun,\n\tyear = {2021},\n\tnote = {Publisher: Public Library of Science},\n\tkeywords = {Amino acid substitution, COVID 19, Genomics, Nucleotides, Phylogenetic analysis, SARS-CoV-2, SNP-array, SOPHiA DDM, Substitution mutation, Uzbekistan},\n\tpages = {e0270314},\n}\n\n

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\n Tracking temporal and spatial genomic changes and evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are among the most urgent research topics worldwide, which help to elucidate the coronavirus disease 2019 (COVID-19) pathogenesis and the effect of deleterious variants. Our current study concentrates genetic diversity of SARS-CoV-2 variants in Uzbekistan and their associations with COVID-19 severity. Thirty-nine whole genome sequences (WGS) of SARS-CoV-2 isolated from PCR-positive patients from Tashkent, Uzbekistan for the period of July-August 2021, were generated and further subjected to further genomic analysis. Genome-wide annotations of clinical isolates from our study have revealed a total of 223 nucleotide-level variations including SNPs and 34 deletions at different positions throughout the entire genome of SARS-CoV-2. These changes included two novel mutations at the Nonstructural protein (Nsp) 13: A85P and Nsp12: Y479N, which were unreported previously. There were two groups of co-occurred substitution patterns: the missense mutations in the Spike (S): D614G, Open Reading Frame (ORF) 1b: P314L, Nsp3: F924, 5`UTR:C241T; Nsp3:P2046L and Nsp3:P2287S, and the synonymous mutations in the Nsp4:D2907 (C8986T), Nsp6:T3646A and Nsp14:A1918V regions, respectively. The “Nextstrain” clustered the largest number of SARS-CoV-2 strains into the Delta clade (n = 32; 82%), followed by two Alpha-originated (n = 4; 10,3%) and 20A (n = 3; 7,7%) clades. Geographically the Delta clade sample sequences were grouped into several clusters with the SARS-CoV genotypes from Russia, Denmark, USA, Egypt and Bangladesh. Phylogenetically, the Delta isolates in our study belong to the two main subclades 21A (56%) and 21J (44%). We found that females were more affected by 21A, whereas males by 21J variant (χ2 = 4.57; p ≤ 0.05, n = 32). The amino acid substitution ORF7a:P45L in the Delta isolates found to be significantly associated with disease severity. In conclusion, this study evidenced that Identified novel substitutions Nsp13: A85P and Nsp12: Y479N, have a destabilizing effect, while missense substitution ORF7a: P45L significantly associated with disease severity.\n

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\n \n\n \n \n \n \n \n \n SCN1A-related epilepsy with recessive inheritance: Ttwo further families.\n \n \n \n \n\n\n \n Moretti, R.; Arnaud, L.; Bouteiller, D.; Trouillard, O.; Moreau, P.; Buratti, J.; Rastetter, A.; Keren, B.; Des Portes, V.; Toulouse, J.; Gourfinkel-An, I.; Leguern, E.; Depienne, C.; Mignot, C.; and Nava, C.\n\n\n \n\n\n\n European Journal of Paediatric Neurology. June 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"SCN1A-related$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{moretti_scn1a-related_2021,\n\ttitle = {{SCN1A}-related epilepsy with recessive inheritance: {Ttwo} further families},\n\tissn = {1090-3798},\n\tshorttitle = {{SCN1A}-related epilepsy with recessive inheritance},\n\turl = {https://www.sciencedirect.com/science/article/pii/S1090379821001227},\n\tdoi = {10.1016/j.ejpn.2021.05.018},\n\tabstract = {Background\nVariants in SCN1A gene, encoding the voltage-gated sodium channel Nav1.1, are associated with distinct epilepsy syndromes ranging from the relatively benign genetic epilepsy with febrile seizures plus (GEFS+) to Dravet syndrome, a severe developmental and epileptic encephalopathy (DEE). Most SCN1A pathogenic variants are heterozygous changes inherited in a dominant or de novo inheritance and many cause a loss-of-function of one allele. To date, recessive inheritance has been suggested in only two families with affected children harboring homozygous SCN1A missense variants while their heterozygous parents were asymptomatic. The aim of this report is to describe two additional families in which affected individuals have biallelic SCN1A variants possibly explaining their phenotype.\nMethods and results\nWe report two novel homozygous SCN1A missense variants in two patients from related parents. Both patients had fever-sensitive epilepsy beginning in the first months of life, followed by afebrile seizures, without severe cognitive impairment. Parents were asymptomatic. Next generation sequencing excluded a pathogenic variant in other genes involved in DEE. Estimation of pathogenicity scores by in-silico tools suggests that the impact of these SCN1A variants is less damaging than that of dominant pathogenic variants.\nConclusion\nThis study provides additional evidence that homozygous variants in SCN1A can cause GEFS+. This recessive inheritance would imply that hypomorphic variants may not necessarily cause epilepsy at the heterozygous state but may decrease the seizure threshold when combined.},\n\tlanguage = {en},\n\turldate = {2021-06-21},\n\tjournal = {European Journal of Paediatric Neurology},\n\tauthor = {Moretti, Raffaella and Arnaud, Lionel and Bouteiller, Delphine and Trouillard, Oriane and Moreau, Patricia and Buratti, Julien and Rastetter, Agnès and Keren, Boris and Des Portes, Vincent and Toulouse, Joseph and Gourfinkel-An, Isabelle and Leguern, Eric and Depienne, Christel and Mignot, Cyril and Nava, Caroline},\n\tmonth = jun,\n\tyear = {2021},\n\tkeywords = {Alamut, Dravet syndrome, Ffebrile seizures, GEFS+, Rrecessive inheritance},\n}\n\n

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\n \n\n \n \n \n \n \n \n Schuurs–Hoeijmakers Syndrome (PACS1 Neurodevelopmental Disorder): Seven Novel Patients and a Review.\n \n \n \n \n\n\n \n Tenorio-Castaño, J.; Morte, B.; Nevado, J.; Martinez-Glez, V.; Santos-Simarro, F.; García-Miñaúr, S.; Palomares-Bralo, M.; Pacio-Míguez, M.; Gómez, B.; Arias, P.; Alcochea, A.; Carrión, J.; Arias, P.; Almoguera, B.; López-Grondona, F.; Lorda-Sanchez, I.; Galán-Gómez, E.; Valenzuela, I.; Méndez Perez, M. P.; Cuscó, I.; Barros, F.; Pié, J.; Ramos, S.; Ramos, F. J.; Kuechler, A.; Tizzano, E.; Ayuso, C.; Kaiser, F. J.; Pérez-Jurado, L. A.; Carracedo, Á.; Consortium, T. E.; Consortium, T. S.; and Lapunzina, P.\n\n\n \n\n\n\n Genes, 12(5): 738. May 2021.\n Number: 5 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Schuurs–Hoeijmakers$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{tenorio-castano_schuurshoeijmakers_2021,\n\ttitle = {Schuurs–{Hoeijmakers} {Syndrome} ({PACS1} {Neurodevelopmental} {Disorder}): {Seven} {Novel} {Patients} and a {Review}},\n\tvolume = {12},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tshorttitle = {Schuurs–{Hoeijmakers} {Syndrome} ({PACS1} {Neurodevelopmental} {Disorder})},\n\turl = {https://www.mdpi.com/2073-4425/12/5/738},\n\tdoi = {10.3390/genes12050738},\n\tabstract = {Schuurs–Hoeijmakers syndrome (SHMS) or PACS1 Neurodevelopmental disorder is a rare disorder characterized by intellectual disability, abnormal craniofacial features and congenital malformations. SHMS is an autosomal dominant hereditary disease caused by pathogenic variants in the PACS1 gene. PACS1 is a trans-Golgi-membrane traffic regulator that directs protein cargo and several viral envelope proteins. It is upregulated during human embryonic brain development and has low expression after birth. So far, only 54 patients with SHMS have been reported. In this work, we report on seven new identified SHMS individuals with the classical c.607C \\&gt; T: p.Arg206Trp PACS1 pathogenic variant and review clinical and molecular aspects of all the patients reported in the literature, providing a summary of clinical findings grouped as very frequent (≥75\\% of patients), frequent (50–74\\%), infrequent (26–49\\%) and rare (less than ≤25\\%).},\n\tlanguage = {en},\n\tnumber = {5},\n\turldate = {2021-05-20},\n\tjournal = {Genes},\n\tauthor = {Tenorio-Castaño, Jair and Morte, Beatriz and Nevado, Julián and Martinez-Glez, Víctor and Santos-Simarro, Fernando and García-Miñaúr, Sixto and Palomares-Bralo, María and Pacio-Míguez, Marta and Gómez, Beatriz and Arias, Pedro and Alcochea, Alba and Carrión, Juan and Arias, Patricia and Almoguera, Berta and López-Grondona, Fermina and Lorda-Sanchez, Isabel and Galán-Gómez, Enrique and Valenzuela, Irene and Méndez Perez, María Pilar and Cuscó, Ivón and Barros, Francisco and Pié, Juan and Ramos, Sergio and Ramos, Feliciano J. and Kuechler, Alma and Tizzano, Eduardo and Ayuso, Carmen and Kaiser, Frank J. and Pérez-Jurado, Luis A. and Carracedo, Ángel and The ENoD-CIBERER Consortium and The SIDE Consortium and Lapunzina, Pablo},\n\tmonth = may,\n\tyear = {2021},\n\tnote = {Number: 5\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {CES, PACS1, Schuurs–Hoeijmakers syndrome, WES, intellectual disability, pathogenic variant c.607C \\&gt, phosphofurin acidic cluster sorting protein 1, rare disorders},\n\tpages = {738},\n}\n\n

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\n \n\n \n \n \n \n \n \n Mutational spectrum of congenital long QT syndrome in Turkey; identification of 12 novel mutations across KCNQ1, KCNH2, SCN5A, KCNJ2, CACNA1C, and CALM1.\n \n \n \n \n\n\n \n Akgun-Dogan, O.; Ağaoğlu, N. B.; K. Demirkol, Y.; Doğanay, L.; Ergül, Y.; and Karacan, M.\n\n\n \n\n\n\n Journal of Cardiovascular Electrophysiology, n/a(n/a). December 2021.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/jce.15306\n\n\n\n
\n\n\n\n \n \n $\"Mutational$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{akgun-dogan_mutational_2021,\n\ttitle = {Mutational spectrum of congenital long {QT} syndrome in {Turkey}; identification of 12 novel mutations across {KCNQ1}, {KCNH2}, {SCN5A}, {KCNJ2}, {CACNA1C}, and {CALM1}},\n\tvolume = {n/a},\n\tissn = {1540-8167},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1111/jce.15306},\n\tdoi = {10.1111/jce.15306},\n\tabstract = {Introduction Long QT syndrome (LQTS) is of great importance as it is the most common cause of sudden cardiac death in childhood. The diagnosis is made by the prolongation of the QTc interval on the electrocardiography. However, clinical heterogeneity and nondiagnostic QTc intervals may cause a delay in the diagnosis. In such cases, genetic tests such as next-generation sequencing (NGS) panel analysis enable a definitive diagnosis. We present the first study that aimed to expand the LQTS's mutational spectrum by NGS panel analysis from Turkey. Methods Fifty-seven unrelated patients with clinically diagnosed LQTS were investigated using an NGS panel that includes six LQTS-related genes. Clinical aspects, outcome, and molecular analysis results were reviewed. Results Pathogenic (53\\%)/likely pathogenic (23\\%)/variant of unknown significance (4\\%) variants were detected in any of the genes examined in 79\\% of the patients. Among all detected variants, KCNQ1(71\\%) was the most common gene, followed by SCN5A (11\\%), KCNH2 (10\\%), CALM1 (5\\%), and CACNA1C (3\\%). Twelve novel variants were detected. Among the variants in KCNQ1, the c.1097G{\\textgreater}A variant was present in 42\\% of patients. This variant also composed 31\\% of the variants detected in all of the genes. Conclusion Our study expands the spectrum of the variations associated with LQTS with twelve novel variants in five genes. And also it draws attention to the frequency of the KCNQ1 c.1097G{\\textgreater}A variant and forms the basis for new studies to determine the possible founder effect in the Turkish population. Furthermore, identifying new variants and clinical findings has importance in elaborating the roles of related genes in pathophysiology and determining the variable expression and incomplete penetration rates in this syndrome.},\n\tlanguage = {en},\n\tnumber = {n/a},\n\turldate = {2022-01-27},\n\tjournal = {Journal of Cardiovascular Electrophysiology},\n\tauthor = {Akgun-Dogan, Ozlem and Ağaoğlu, Nihat B. and K. Demirkol, Yasemin and Doğanay, Levent and Ergül, Yakup and Karacan, Mehmet},\n\tmonth = dec,\n\tyear = {2021},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/jce.15306},\n\tkeywords = {Extended Cardio Solution, Turkey, children, genetic testing, long QT syndrome, next-generation sequencing},\n}\n\n

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\n \n\n \n \n \n \n \n \n Pregnancy onset congenital thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome) mimicking HELLP syndrome: a case report.\n \n \n \n \n\n\n \n Ergin, B.; Kobal, B. B.; Yazıcı, Z.; Kaya, A. H.; Canbek, S.; Muhcu, M.; and Özel, A.\n\n\n \n\n\n\n Perinatal Journal, 29(3). December 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Pregnancy$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{ergin_pregnancy_2021,\n\ttitle = {Pregnancy onset congenital thrombotic thrombocytopenic purpura ({Upshaw}-{Schulman} syndrome) mimicking {HELLP} syndrome: a case report},\n\tvolume = {29},\n\turl = {http://www.perinataljournal.com/Archive/Article/20210293013},\n\tabstract = {Objective:\nThrombotic thrombocytopenic purpura is a thrombotic microangiopathic condition characterized by hemolytic anemia, thrombocytopenia, neurologic abnormalities, fever and renal dysfunction. Thrombotic microangiopathies such as preeclampsia and HELLP syndrome are pregnancy-specific, whereas others such as thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome are not. In this report, we present a case at which we identified a novel mutation which led to a significant reduction of ADAMTS13 activity.\nCase(s):\nA nulliparous pregnant woman of 32-year-old presenting with epigastric pain, hypertension and low platelet count was first suspected of HELLP syndrome, but was diagnosed with congenital TTP after delivery.\nConclusion:\nHELLP syndrome co-existed with undiagnosed TTP in this case. We strive to have sufficient awareness in order to distinguish these two pathologies from each other on an antenatal basis, because the causes of the managements are entirely different.\nKeywords: ADAMTS13 activity, congenital thrombotic thrombocytopenic purpura, HELLP syndrome, outcome, plasmapheresis, pregnancy.},\n\tnumber = {3},\n\turldate = {2022-01-17},\n\tjournal = {Perinatal Journal},\n\tauthor = {Ergin, Başak and Kobal, Berna Buse and Yazıcı, Zeynep and Kaya, Ali Hakan and Canbek, Sezin and Muhcu, Murat and Özel, Ayşegül},\n\tmonth = dec,\n\tyear = {2021},\n\tkeywords = {Clinical Exome},\n}\n\n

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\n \n\n \n \n \n \n \n \n Genetic Variants Assessing Crohn’s Disease Pattern in Pediatric Inflammatory Bowel Disease Patients by a Clinical Exome Survey.\n \n \n \n \n\n\n \n Noel, D. D.; Marinella, P.; Mauro, G.; Tripodi, S. I.; Pin, A.; Serena, A.; Matteo, B.; Giuseppe, F. M.; Patrizia, A.; Stefano, C.; Tommasini, A.; and Raffaele, B.\n\n\n \n\n\n\n Bioinformatics and Biology Insights, 15: 11779322211055285. December 2021.\n Publisher: SAGE Publications Ltd STM\n\n\n\n
\n\n\n\n \n \n $\"Genetic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 7 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{noel_genetic_2021,\n\ttitle = {Genetic {Variants} {Assessing} {Crohn}’s {Disease} {Pattern} in {Pediatric} {Inflammatory} {Bowel} {Disease} {Patients} by a {Clinical} {Exome} {Survey}},\n\tvolume = {15},\n\tissn = {1177-9322},\n\turl = {https://doi.org/10.1177/11779322211055285},\n\tdoi = {10.1177/11779322211055285},\n\tabstract = {Background:Inflammatory bowel diseases (IBDs) are complex, multifactorial disorders that comprise Crohn?s disease (CD) and ulcerative colitis (UC). Recent discoveries have brought much attention to the genetic predisposition of patients with IBD. Here we evaluate the interaction between IBD genetic risk factors susceptibility and CD occurrence in an IBD pediatric patient population, performing a clinical exome survey.Methods:From February 2018 to April 2019, we collected blood samples from 7 pediatric patients with IBD concerns from several collaborating health centers and/or hospitals. Blood samples were processed by extracting and sequencing DNA for a clinical exome survey. Shophia-DDM-v3-4 platform allowed sequenced reads alignment on hg19 genome as well as genetic variant calling. Both IBD risk and pathogenic genetic variants covered by at least 20 reads were selected for subjacent analysis.Results:Normality and Bartlett tests of both risk and pathogenic genetic variants suggested random and heterogeneous distribution of these variants in this group of IBD pediatric patients. P value clustering analysis by processing 157 IBD risk factors revealed genetic heterogeneity in IBD population and suggested two pathways influencing IBD development. In particular, (1) genetic variants associated with autoimmune and (2) metabolic diseases and CD risk factors (rs2066844 and rs2241880 single nucleotide polymorphism variants, respectively, of genes NOD2 and ATG16L) were identified in distinct clusters of IBD patients (P?},\n\tlanguage = {en},\n\turldate = {2022-01-17},\n\tjournal = {Bioinformatics and Biology Insights},\n\tauthor = {Noel, Dago Dougba and Marinella, Pinelli and Mauro, Giacomelli and Tripodi, Serena Ilaria and Pin, Alessia and Serena, Arrigo and Matteo, Bramuzzo and Giuseppe, Fuoti Maurizio and Patrizia, Alvisi and Stefano, Calza and Tommasini, Alberto and Raffaele, Badolato},\n\tmonth = dec,\n\tyear = {2021},\n\tnote = {Publisher: SAGE Publications Ltd STM},\n\tkeywords = {Clinical Exome, Crohn’s disease, Inflammatory bowel disease, NGS-next generation sequencing, genetic variants, pediatric patients},\n\tpages = {11779322211055285},\n}\n\n

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\n \n\n \n \n \n \n \n \n Silent variant in F8:c.222G\\textgreaterT (p.Thr74Thr) causes a partial exon skipping in a patient with mild hemophilia A.\n \n \n \n \n\n\n \n Letelier, A.; Ljung, R.; Olsson, A.; and Andersson, N. G.\n\n\n \n\n\n\n Molecular Genetics & Genomic Medicine, n/a(n/a): e1856. December 2021.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/mgg3.1856\n\n\n\n
\n\n\n\n \n \n $\"Silent$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{letelier_silent_2021,\n\ttitle = {Silent variant in {F8}:c.{222G}{\\textgreater}{T} (p.{Thr74Thr}) causes a partial exon skipping in a patient with mild hemophilia {A}},\n\tvolume = {n/a},\n\tissn = {2324-9269},\n\tshorttitle = {Silent variant in {F8}},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/mgg3.1856},\n\tdoi = {10.1002/mgg3.1856},\n\tabstract = {One of the challenges of genetic testing in patients with hemophilia A is the interpretation of sequence variants. Here we report a silent variant found in exon 2 in the F8 gene in a 47-year-old patient with a previous von Willebrand disease (VWD) type 1 diagnosis. Clinically he had mild bleeding symptoms restricted to prolonged bleeding from minor wounds. Sanger sequencing of F8 gene using genomic DNA showed a hemizygous silent variant in exon 2: c.222G{\\textgreater}T, p.Thr74Thr. When applying ACMG criteria, the variant was predicted to be “likely benign” in the analyzing software or VUS after curating. Sanger sequencing of the patient's cDNA after nested polymerase chain reaction showed that the patient had both a normal transcript containing exons 1–4 and a defect transcript lacking exon 2. These findings explain the patient's low FVIII:C level and led to the diagnosis of mild hemophilia A instead of VWD type 1. This case illustrates that mRNA work-up may be needed to clarify a patient's phenotype–genotype.},\n\tlanguage = {en},\n\tnumber = {n/a},\n\turldate = {2022-01-17},\n\tjournal = {Molecular Genetics \\& Genomic Medicine},\n\tauthor = {Letelier, Anna and Ljung, Rolf and Olsson, Anna and Andersson, Nadine G.},\n\tmonth = dec,\n\tyear = {2021},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/mgg3.1856},\n\tkeywords = {Alamut, F8 gene, exon skipping, hemophilia A, silent mutation},\n\tpages = {e1856},\n}\n\n

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\n \n\n \n \n \n \n \n \n Mutation profile of SARS-CoV-2 genome in a sample from the first year of the pandemic in Colombia.\n \n \n \n \n\n\n \n Gálvez, J. M.; Chaparro-Solano, H. M.; Pinzón-Rondón, Á. M.; Albornoz, L. L.; Pardo-Oviedo, J. M.; Zapata-Gómez, F. A.; Patiño-Aldana, A. F.; Hernández-Rodríguez, A. d. P.; Díaz-Quiroz, M.; and Ruiz-Sternberg, Á. M.\n\n\n \n\n\n\n Infection, Genetics and Evolution, 97: 105192. December 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Mutation$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{galvez_mutation_2021,\n\ttitle = {Mutation profile of {SARS}-{CoV}-2 genome in a sample from the first year of the pandemic in {Colombia}},\n\tvolume = {97},\n\tissn = {1567-1348},\n\turl = {https://www.sciencedirect.com/science/article/pii/S1567134821004925},\n\tdoi = {10.1016/j.meegid.2021.105192},\n\tabstract = {The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is the etiopathogenic agent of COVID-19, a condition that has led to a formally recognized pandemic by March 2020 (World Health Organization –WHO). The SARS-CoV-2 genome is constituted of 29,903 base pairs, that code for four structural proteins (N, M, S, and E) and more than 20 non-structural proteins. Mutations in any of these regions, especially in those that encode for the structural proteins, have allowed the identification of diverse lineages around the world, some of them named as Variants of Concern (VOC) and Variants of Interest (VOI), according to the WHO and CDC. In this study, by using Next Generation Sequencing (NGS) technology, we sequenced the SARS-CoV-2 genome of 422 samples from Colombian residents, all of them collected between April 2020 and January 2021. We obtained genetic information from 386 samples, leading us to the identification of 14 new lineages circulating in Colombia, 13 of which were identified for the first time in South America. GH was the predominant GISAID clade in our sample. Most mutations were either missense (53.6\\%) or synonymous mutations (37.4\\%), and most genetic changes were located in the ORF1ab gene (63.9\\%), followed by the S gene (12.9\\%). In the latter, we identified mutations E484K, L18F, and D614G. Recent evidence suggests that these mutations concede important particularities to the virus, compromising host immunity, the diagnostic test performance, and the effectiveness of some vaccines. Some important lineages containing these mutations are the Alpha, Beta, and Gamma (WHO Label). Further genomic surveillance is important for the understanding of emerging genomic variants and their correlation with disease severity.},\n\tlanguage = {en},\n\turldate = {2022-01-06},\n\tjournal = {Infection, Genetics and Evolution},\n\tauthor = {Gálvez, Jubby Marcela and Chaparro-Solano, Henry Mauricio and Pinzón-Rondón, Ángela María and Albornoz, Ludwig L. and Pardo-Oviedo, Juan Mauricio and Zapata-Gómez, Fabio Andrés and Patiño-Aldana, Andrés Felipe and Hernández-Rodríguez, Andrea del Pila and Díaz-Quiroz, Mateo and Ruiz-Sternberg, Ángela María},\n\tmonth = dec,\n\tyear = {2021},\n\tkeywords = {Covid-19, Genetic variation, High-throughput nucleotide sequencing, SARS-CoV-2, SARS-CoV-2 genome, SARS-CoV-2 variants, Whole genome sequencing},\n\tpages = {105192},\n}\n\n

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\n \n\n \n \n \n \n \n \n Role of Q675H Mutation in Improving SARS-CoV-2 Spike Interaction with the Furin Binding Pocket.\n \n \n \n \n\n\n \n Bertelli, A.; D’Ursi, P.; Campisi, G.; Messali, S.; Milanesi, M.; Giovanetti, M.; Ciccozzi, M.; Caccuri, F.; and Caruso, A.\n\n\n \n\n\n\n Viruses, 13(12): 2511. December 2021.\n Number: 12 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Role$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{bertelli_role_2021,\n\ttitle = {Role of {Q675H} {Mutation} in {Improving} {SARS}-{CoV}-2 {Spike} {Interaction} with the {Furin} {Binding} {Pocket}},\n\tvolume = {13},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\turl = {https://www.mdpi.com/1999-4915/13/12/2511},\n\tdoi = {10.3390/v13122511},\n\tabstract = {Genotype screening was implemented in Italy and showed a significant prevalence of new SARS-CoV-2 mutants carrying Q675H mutation, near the furin cleavage site of spike protein. Currently, this mutation, which is expressed on different SARS-CoV-2 lineages circulating worldwide, has not been thoughtfully investigated. Therefore, we performed phylogenetic and biocomputational analysis to better understand SARS-CoV-2 Q675H mutants\\&rsquo; evolutionary relationships with other circulating lineages and Q675H function in its molecular context. Our studies reveal that Q675H spike mutation is the result of parallel evolution because it arose independently in separate evolutionary clades. In silico data show that the Q675H mutation gives rise to a hydrogen-bonds network in the spike polar region. This results in an optimized directionality of arginine residues involved in interaction of spike with the furin binding pocket, thus improving proteolytic exposure of the viral protein. Furin was predicted to have a greater affinity for Q675H than Q675 substrate conformations. As a consequence, Q675H mutation could confer a fitness advantage to SARS-CoV-2 by promoting a more efficient viral entry. Interestingly, here we have shown that Q675H spike mutation is documented in all the VOCs. This finding highlights that VOCs are still evolving to enhance viral fitness and to adapt to the human host. At the same time, it may suggest Q675H spike mutation involvement in SARS-CoV-2 evolution.},\n\tlanguage = {en},\n\tnumber = {12},\n\turldate = {2022-01-06},\n\tjournal = {Viruses},\n\tauthor = {Bertelli, Anna and D’Ursi, Pasqualina and Campisi, Giovanni and Messali, Serena and Milanesi, Maria and Giovanetti, Marta and Ciccozzi, Massimo and Caccuri, Francesca and Caruso, Arnaldo},\n\tmonth = dec,\n\tyear = {2021},\n\tnote = {Number: 12\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Q675H spike mutation, SARS-CoV-2, SARS-CoV2, VOC, furin cleavage, molecular dynamics, phylogenesis, sars},\n\tpages = {2511},\n}\n\n

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\n \n\n \n \n \n \n \n \n WNT11, a new gene associated with early-onset osteoporosis, is required for osteoblastogenesis.\n \n \n \n \n\n\n \n Silva, C. C.; Edouard, T.; Fradin, M.; Aubert-Mucca, M.; Ricquebourg, M.; Raman, R.; Salles, J. P.; Charon, V.; Guggenbuhl, P.; Muller, M.; Cohen-Solal, M.; and Collet, C.\n\n\n \n\n\n\n Human Molecular Genetics,ddab349. December 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"WNT11,$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{silva_wnt11_2021,\n\ttitle = {{WNT11}, a new gene associated with early-onset osteoporosis, is required for osteoblastogenesis},\n\tissn = {0964-6906},\n\turl = {https://doi.org/10.1093/hmg/ddab349},\n\tdoi = {10.1093/hmg/ddab349},\n\tabstract = {Monogenic early-onset osteoporosis (EOOP) is a rare disease defined by low bone mineral density (BMD) that results in increased risk of fracture in children and young adults. Although several causative genes have been identified, some of the EOOP causation remains unresolved. Whole-exome sequencing revealed a de novo heterozygous loss-of-function mutation in WNT11 (NM\\_004626.2:c.677\\_678dup p.Leu227Glyfs*22) in a 4-year-old boy with low BMD and fractures. We identified two heterozygous WNT11 missense variants (NM\\_004626.2:c.217G \\&gt; A p.Ala73Thr) and (NM\\_004626.2:c.865G \\&gt; A p.Val289Met) in a 51-year-old woman and in a 61-year-old woman respectively, both with bone fragility. U2OS cells with heterozygous WNT11 mutation (NM\\_004626.2:c.690\\_721delfs*40) generated by CRISPR-Cas9 showed reduced cell proliferation (30\\%) and osteoblast differentiation (80\\%) as compared with wild-type U2OS cells. The expression of genes in the Wnt canonical and non-canonical pathways was inhibited in these mutant cells, but recombinant WNT11 treatment rescued the expression of Wnt pathway target genes. Furthermore, the expression of RSPO2, a WNT11 target involved in bone cell differentiation, and its receptor LGR5, was decreased in WNT11 mutant cells. Treatment with WNT5A and WNT11 recombinant proteins reversed LGR5 expression, but WNT3A recombinant protein treatment had no effect on LGR5 expression in mutant cells. Moreover, treatment with recombinant RSPO2 but not WNT11 or WNT3A activated the canonical pathway in mutant cells. In conclusion, we have identified WNT11 as a new gene responsible for EOOP, with loss-of-function variant inhibiting bone formation via Wnt canonical and non-canonical pathways. WNT11 may activate Wnt signaling by inducing the RSPO2–LGR5 complex via the non-canonical Wnt pathway.},\n\turldate = {2021-12-14},\n\tjournal = {Human Molecular Genetics},\n\tauthor = {Silva, Caroline Caetano and Edouard, Thomas and Fradin, Melanie and Aubert-Mucca, Marion and Ricquebourg, Manon and Raman, Ratish and Salles, Jean Pierre and Charon, Valérie and Guggenbuhl, Pascal and Muller, Marc and Cohen-Solal, Martine and Collet, Corinne},\n\tmonth = dec,\n\tyear = {2021},\n\tkeywords = {Alamut},\n\tpages = {ddab349},\n}\n\n

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\n \n\n \n \n \n \n \n \n The ACMG SF v3.0 gene list increases returnable variant detection by 22% when compared with v2.0 in the ClinSeq cohort.\n \n \n \n \n\n\n \n Johnston, J. J.; Brennan, M.; Radenbaugh, B.; Yoo, S. J.; Hernandez, S. M.; Lewis, K. L.; Katz, A. E.; Manolio, T. A.; and Biesecker, L. G.\n\n\n \n\n\n\n Genetics in Medicine, 0(0). December 2021.\n Publisher: Elsevier\n\n\n\n
\n\n\n\n \n \n $\"The$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{johnston_acmg_2021,\n\ttitle = {The {ACMG} {SF} v3.0 gene list increases returnable variant detection by 22\\% when compared with v2.0 in the {ClinSeq} cohort},\n\tvolume = {0},\n\tissn = {1098-3600, 1530-0366},\n\turl = {https://www.gimjournal.org/article/S1098-3600(21)05390-9/fulltext},\n\tdoi = {10.1016/j.gim.2021.11.012},\n\tlanguage = {English},\n\tnumber = {0},\n\turldate = {2021-12-14},\n\tjournal = {Genetics in Medicine},\n\tauthor = {Johnston, Jennifer J. and Brennan, Marie-Luise and Radenbaugh, Bailey and Yoo, Seeley J. and Hernandez, Sophia M. and Lewis, Katie L. and Katz, Alexander E. and Manolio, Teri A. and Biesecker, Leslie G.},\n\tmonth = dec,\n\tyear = {2021},\n\tnote = {Publisher: Elsevier},\n\tkeywords = {ACMG SF v3.0, Alamut, ClinSeq, Reverse phenotyping, Secondary findings, Variant classification},\n}\n\n

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\n \n\n \n \n \n \n \n \n Galaxy Is a Suitable Bioinformatics Platform for the Molecular Diagnosis of Human Genetic Disorders Using High-Throughput Sequencing Data Analysis. Five Years of Experience in a Clinical Laboratory.\n \n \n \n \n\n\n \n Chappell, K.; Francou, B.; Habib, C.; Huby, T.; Leoni, M.; Cottin, A.; Nadal, F.; Adnet, E.; Paoli, E.; Oliveira, C.; Verstuyft, C.; Davit-Spraul, A.; Gaignard, P.; Lebigot, E.; Duclos-Vallee, J.; Young, J.; Kamenicky, P.; Adams, D.; Echaniz-Laguna, A.; Gonzales, E.; Bouvattier, C.; Linglart, A.; Picard, V.; Bergoin, E.; Jacquemin, E.; Guiochon-Mantel, A.; Proust, A.; and Bouligand, J.\n\n\n \n\n\n\n Clinical Chemistry,hvab220. June 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Galaxy$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{chappell_galaxy_2021,\n\ttitle = {Galaxy {Is} a {Suitable} {Bioinformatics} {Platform} for the {Molecular} {Diagnosis} of {Human} {Genetic} {Disorders} {Using} {High}-{Throughput} {Sequencing} {Data} {Analysis}. {Five} {Years} of {Experience} in a {Clinical} {Laboratory}},\n\tissn = {0009-9147},\n\turl = {https://doi.org/10.1093/clinchem/hvab220},\n\tdoi = {10.1093/clinchem/hvab220},\n\tabstract = {To date, the usage of Galaxy, an open-source bioinformatics platform, has been reported primarily in research. We report 5 years’ experience (2015 to 2020) with Galaxy in our hospital, as part of the “Assistance Publique–Hôpitaux de Paris” (AP-HP), to demonstrate its suitability for high-throughput sequencing (HTS) data analysis in a clinical laboratory setting.Our Galaxy instance has been running since July 2015 and is used daily to study inherited diseases, cancer, and microbiology. For the molecular diagnosis of hereditary diseases, 6970 patients were analyzed with Galaxy (corresponding to a total of 7029 analyses).Using Galaxy, the time to process a batch of 23 samples—equivalent to a targeted DNA sequencing MiSeq run—from raw data to an annotated variant call file was generally less than 2 h for panels between 1 and 500 kb. Over 5 years, we only restarted the server twice for hardware maintenance and did not experience any significant troubles, demonstrating the robustness of our Galaxy installation in conjunction with HTCondor as a job scheduler and a PostgreSQL database. The quality of our targeted exome sequencing method was externally evaluated annually by the European Molecular Genetics Quality Network (EMQN). Sensitivity was mean (SD)\\% 99 (2)\\% for single nucleotide variants and 93 (9)\\% for small insertion-deletions.Our experience with Galaxy demonstrates it to be a suitable platform for HTS data analysis with vast potential to benefit patient care in a clinical laboratory setting.},\n\turldate = {2021-12-14},\n\tjournal = {Clinical Chemistry},\n\tauthor = {Chappell, Kenneth and Francou, Bruno and Habib, Christophe and Huby, Thomas and Leoni, Marco and Cottin, Aurélien and Nadal, Florian and Adnet, Eric and Paoli, Eric and Oliveira, Christophe and Verstuyft, Céline and Davit-Spraul, Anne and Gaignard, Pauline and Lebigot, Elise and Duclos-Vallee, Jean-Charles and Young, Jacques and Kamenicky, Peter and Adams, David and Echaniz-Laguna, Andoni and Gonzales, Emmanuel and Bouvattier, Claire and Linglart, Agnes and Picard, Véronique and Bergoin, Emilie and Jacquemin, Emmanuel and Guiochon-Mantel, Anne and Proust, Alexis and Bouligand, Jérôme},\n\tmonth = jun,\n\tyear = {2021},\n\tkeywords = {Alamut},\n\tpages = {hvab220},\n}\n\n

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\n \n\n \n \n \n \n \n \n Mismatch repair deficiency in early-onset duodenal, ampullary, and pancreatic carcinomas is a strong indicator for a hereditary defect.\n \n \n \n \n\n\n \n Kryklyva, V.; Brosens, L. A.; Marijnissen-van Zanten, M. A.; Ligtenberg, M. J.; and Nagtegaal, I. D\n\n\n \n\n\n\n The Journal of Pathology: Clinical Research, n/a(n/a). December 2021.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/cjp2.252\n\n\n\n
\n\n\n\n \n \n $\"Mismatch$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{kryklyva_mismatch_2021,\n\ttitle = {Mismatch repair deficiency in early-onset duodenal, ampullary, and pancreatic carcinomas is a strong indicator for a hereditary defect},\n\tvolume = {n/a},\n\tissn = {2056-4538},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/cjp2.252},\n\tdoi = {10.1002/cjp2.252},\n\tabstract = {Mismatch repair deficiency (dMMR) is a hallmark of Lynch syndrome (LS), but its prevalence in early-onset (diagnosed under the age of 50 years) duodenal, ampullary, and pancreatic carcinomas (DC, AC, and PC, respectively) is largely unknown. We explored the prevalence of dMMR and the underlying molecular mechanisms in a retrospectively collected cohort of 90 early-onset carcinomas of duodenal, ampullary, and pancreatic origin. dMMR was most prevalent in early-onset DCs (47.8\\%); more than half of those were associated with hereditary cancer syndromes (LS or constitutional mismatch repair deficiency syndrome). All dMMR AC and PC were due to LS. Concordance of dMMR with underlying hereditary condition warrants ubiquitous dMMR testing in all early-onset DC, AC, and PC.},\n\tlanguage = {en},\n\tnumber = {n/a},\n\turldate = {2021-12-14},\n\tjournal = {The Journal of Pathology: Clinical Research},\n\tauthor = {Kryklyva, Valentyna and Brosens, Lodewijk AA and Marijnissen-van Zanten, Monica AJ and Ligtenberg, Marjolijn JL and Nagtegaal, Iris D},\n\tmonth = dec,\n\tyear = {2021},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/cjp2.252},\n\tkeywords = {Alamut, Lynch syndrome, constitutional mismatch repair deficiency syndrome, early-onset ampullary carcinoma, early-onset duodenal carcinoma, early-onset pancreatic carcinoma, germline variants, microsatellite instability, mismatch repair deficiency},\n}\n\n

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\n \n\n \n \n \n \n \n \n Genomic and clinical findings in myeloid neoplasms with PDGFRB rearrangement.\n \n \n \n \n\n\n \n Di Giacomo, D.; Quintini, M.; Pierini, V.; Pellanera, F.; La Starza, R.; Gorello, P.; Matteucci, C.; Crescenzi, B.; Fiumara, P. F.; Veltroni, M.; Borlenghi, E.; Albano, F.; Forghieri, F.; Maccaferri, M.; Bettelli, F.; Luppi, M.; Cuneo, A.; Rossi, G.; and Mecucci, C.\n\n\n \n\n\n\n Annals of Hematology. December 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Genomic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{di_giacomo_genomic_2021,\n\ttitle = {Genomic and clinical findings in myeloid neoplasms with {PDGFRB} rearrangement},\n\tissn = {1432-0584},\n\turl = {https://doi.org/10.1007/s00277-021-04712-8},\n\tdoi = {10.1007/s00277-021-04712-8},\n\tabstract = {Platelet-derived growth factor receptor B (PDGFRB) gene rearrangements define a unique subgroup of myeloid and lymphoid neoplasms frequently associated with eosinophilia and characterized by high sensitivity to tyrosine kinase inhibition. To date, various PDGFRB/5q32 rearrangements, involving at least 40 fusion partners, have been reported. However, information on genomic and clinical features accompanying rearrangements of PDGFRB is still scarce. Here, we characterized a series of 14 cases with a myeloid neoplasm using cytogenetic, single nucleotide polymorphism array, and next-generation sequencing. We identified nine PDGFRB translocation partners, including the KAZN gene at 1p36.21 as a novel partner in a previously undescribed t(1;5)(p36;q33) chromosome change. In all cases, the PDGFRB recombination was the sole cytogenetic abnormality underlying the phenotype. Acquired somatic variants were mainly found in clinically aggressive diseases and involved epigenetic genes (TET2, DNMT3A, ASXL1), transcription factors (RUNX1 and CEBPA), and signaling modulators (HRAS). By using both cytogenetic and nested PCR monitoring to evaluate response to imatinib, we found that, in non-AML cases, a low dosage (100–200 mg) is sufficient to induce and maintain longstanding hematological, cytogenetic, and molecular remissions.},\n\tlanguage = {en},\n\turldate = {2021-12-14},\n\tjournal = {Annals of Hematology},\n\tauthor = {Di Giacomo, Danika and Quintini, Martina and Pierini, Valentina and Pellanera, Fabrizia and La Starza, Roberta and Gorello, Paolo and Matteucci, Caterina and Crescenzi, Barbara and Fiumara, Paolo Fabio and Veltroni, Marinella and Borlenghi, Erika and Albano, Francesco and Forghieri, Fabio and Maccaferri, Monica and Bettelli, Francesca and Luppi, Mario and Cuneo, Antonio and Rossi, Giuseppe and Mecucci, Cristina},\n\tmonth = dec,\n\tyear = {2021},\n\tkeywords = {MYS, SOPHiA DDM},\n}\n\n

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\n \n\n \n \n \n \n \n \n Molecular detection of SARS-CoV-2 eta VOI in Northern Italy: a case report.\n \n \n \n \n\n\n \n Broccolo, F.; Giovanetti, M.; Colombo, A.; Perrelli, N.; Bussini, A.; Cavalli, S.; Ciccozzi, M.; and Zollo, M.\n\n\n \n\n\n\n Clinical Chemistry and Laboratory Medicine (CCLM). December 2021.\n Publisher: De Gruyter\n\n\n\n
\n\n\n\n \n \n $\"Molecular$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{broccolo_molecular_2021,\n\ttitle = {Molecular detection of {SARS}-{CoV}-2 eta {VOI} in {Northern} {Italy}: a case report},\n\tissn = {1437-4331},\n\tshorttitle = {Molecular detection of {SARS}-{CoV}-2 eta {VOI} in {Northern} {Italy}},\n\turl = {https://www.degruyter.com/document/doi/10.1515/cclm-2021-1230/html},\n\tdoi = {10.1515/cclm-2021-1230},\n\tabstract = {Article Molecular detection of SARS-CoV-2 eta VOI in Northern Italy: a case report was published on December 2, 2021 in the journal Clinical Chemistry and Laboratory Medicine (CCLM) (volume 0, issue 0).},\n\tlanguage = {en},\n\turldate = {2021-12-14},\n\tjournal = {Clinical Chemistry and Laboratory Medicine (CCLM)},\n\tauthor = {Broccolo, Francesco and Giovanetti, Marta and Colombo, Alessio and Perrelli, Nicola and Bussini, Adelaide and Cavalli, Silvia and Ciccozzi, Massimo and Zollo, Massimo},\n\tmonth = dec,\n\tyear = {2021},\n\tnote = {Publisher: De Gruyter},\n\tkeywords = {B.1.525, COVID-19, SARS-CoV-2, eta variant, genomic epidemiology, sars},\n}\n\n

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\n \n\n \n \n \n \n \n \n Male Breast Cancer Review. A Rare Case of Pure DCIS: Imaging Protocol, Radiomics and Management.\n \n \n \n \n\n\n \n Tari, D. U.; Morelli, L.; Guida, A.; and Pinto, F.\n\n\n \n\n\n\n Diagnostics, 11(12): 2199. November 2021.\n Number: 12 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Male$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{tari_male_2021,\n\ttitle = {Male {Breast} {Cancer} {Review}. {A} {Rare} {Case} of {Pure} {DCIS}: {Imaging} {Protocol}, {Radiomics} and {Management}},\n\tvolume = {11},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tshorttitle = {Male {Breast} {Cancer} {Review}. {A} {Rare} {Case} of {Pure} {DCIS}},\n\turl = {https://www.mdpi.com/2075-4418/11/12/2199},\n\tdoi = {10.3390/diagnostics11122199},\n\tabstract = {Ductal carcinoma in situ (DCIS) of male breast is a rare lesion, often associated with invasive carcinoma. When the in situ component is present in pure form, histological grade is usually low or intermediate. Imaging is difficult as gynaecomastia is often present and can mask underlying findings. We report a rare case of pure high-grade DCIS in a young male patient, with associated intraductal papilloma and atypical ductal hyperplasia. Digital breast tomosynthesis (DBT) showed an area of architectural distortion at the union of outer quadrants of the left breast without gynaecomastia. Triple assessment suggested performing a nipple-sparing mastectomy, which revealed the presence of a focal area of high-grade DCIS of 2 mm. DCIS, even of high grade, is difficult to detect with mammography and even more rare, especially when associated with other proliferative lesions. DBT with 2D synthetic reconstruction is useful as the imaging step of a triple assessment and it should be performed in both symptomatic and asymptomatic high-risk men to differentiate between malignant and benign lesions. We propose a diagnostic model to early detect breast cancer in men, optimizing resources according to efficiency, effectiveness and economy, and look forward to radiomics as a powerful tool to help radiologists.},\n\tlanguage = {en},\n\tnumber = {12},\n\turldate = {2021-12-06},\n\tjournal = {Diagnostics},\n\tauthor = {Tari, Daniele Ugo and Morelli, Luigi and Guida, Antonella and Pinto, Fabio},\n\tmonth = nov,\n\tyear = {2021},\n\tnote = {Number: 12\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {breast neoplasms, clinical practice patterns, digital breast tomosynthesis, ductal carcinoma in situ, guidelines, male breast cancer, proliferative disease of the breast, radiomics},\n\tpages = {2199},\n}\n\n

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\n \n\n \n \n \n \n \n \n Incorporation of next-generation sequencing in clinical practice using solid and liquid biopsy for patients with non-Hodgkin’s lymphoma.\n \n \n \n \n\n\n \n Bastos-Oreiro, M.; Suárez-González, J.; Andrés-Zayas, C.; Carrión, N. C.; Moreno, S.; Carbonell, D.; Chicano, M.; Muñiz, P.; Sanz, L.; Diaz-Crespo, F. J.; Menarguez, J.; Diez-Martín, J. L.; Buño, I.; and Martínez-Laperche, C.\n\n\n \n\n\n\n Scientific Reports, 11(1): 22815. November 2021.\n Bandiera_abtest: a Cc_license_type: cc_by Cg_type: Nature Research Journals Number: 1 Primary_atype: Research Publisher: Nature Publishing Group Subject_term: B-cell lymphoma;Cancer genetics Subject_term_id: b-cell-lymphoma;cancer-genetics\n\n\n\n
\n\n\n\n \n \n $\"Incorporation$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{bastos-oreiro_incorporation_2021,\n\ttitle = {Incorporation of next-generation sequencing in clinical practice using solid and liquid biopsy for patients with non-{Hodgkin}’s lymphoma},\n\tvolume = {11},\n\tcopyright = {2021 The Author(s)},\n\tissn = {2045-2322},\n\turl = {https://www.nature.com/articles/s41598-021-02362-4},\n\tdoi = {10.1038/s41598-021-02362-4},\n\tabstract = {Although next-generation sequencing (NGS) data on lymphomas require further validation before being implemented in daily practice, the clinical application of NGS can be considered right around the corner. The aim of our study was to validate an NGS lymphoid panel for tissue and liquid biopsy with the most common types of non-Hodgkin’s lymphoma [follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL)]. In this series, 372 somatic alterations were detected in 93.6\\% (44/47) of the patients through tissue biopsy. In FL, we identified 93 somatic alterations, with a median of 7.4 mutations per sample. In DLBCL, we detected 279 somatic variants with a median of 8.6 mutations (range 0–35). In 92\\% (24/26) of the cases, we were able to detect some variant in the circulating tumor DNA. We detected a total of 386 variants; 63.7\\% were detected in both types of samples, 13.2\\% were detected only in the circulating tumor DNA, and 23\\% were detected only in the tissue biopsy. We found a correlation between the number of circulating tumor DNA mutations, advanced stage, and bulky disease. The genetic alterations detected in this panel were consistent with those previously described at diagnosis. The liquid biopsy sample is therefore a complementary tool that can provide new genetic information, even in cases where a solid biopsy cannot be performed or an insufficient sample was obtained. In summary, we describe and analyze in this study the findings and difficulties encountered when incorporating liquid biopsy into clinical practice in non-Hodgkin’s lymphoma at diagnosis.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2021-12-02},\n\tjournal = {Scientific Reports},\n\tauthor = {Bastos-Oreiro, Mariana and Suárez-González, Julia and Andrés-Zayas, Cristina and Carrión, Natalia Carolina and Moreno, Solsiré and Carbonell, Diego and Chicano, María and Muñiz, Paula and Sanz, Laura and Diaz-Crespo, Francisco Javier and Menarguez, Javier and Diez-Martín, José Luis and Buño, Ismael and Martínez-Laperche, Carolina},\n\tmonth = nov,\n\tyear = {2021},\n\tnote = {Bandiera\\_abtest: a\nCc\\_license\\_type: cc\\_by\nCg\\_type: Nature Research Journals\nNumber: 1\nPrimary\\_atype: Research\nPublisher: Nature Publishing Group\nSubject\\_term: B-cell lymphoma;Cancer genetics\nSubject\\_term\\_id: b-cell-lymphoma;cancer-genetics},\n\tkeywords = {B-cell lymphoma, Cancer genetics, LYS, SOPHiA DDM},\n\tpages = {22815},\n}\n\n

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\n \n\n \n \n \n \n \n \n TBK1 haploinsufficiency results in changes in the K63-ubiquitination profiles in brain and fibroblasts from affected and presymptomatic mutation carriers.\n \n \n \n \n\n\n \n Khoshnood, B.; Ullgren, A.; Laffita-Mesa, J.; Öijerstedt, L.; Patra, K.; Nennesmo, I.; and Graff, C.\n\n\n \n\n\n\n Journal of Neurology. November 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"TBK1$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{khoshnood_tbk1_2021,\n\ttitle = {{TBK1} haploinsufficiency results in changes in the {K63}-ubiquitination profiles in brain and fibroblasts from affected and presymptomatic mutation carriers},\n\tissn = {1432-1459},\n\turl = {https://doi.org/10.1007/s00415-021-10887-x},\n\tdoi = {10.1007/s00415-021-10887-x},\n\tabstract = {Frontotemporal dementia (FTD) is a neurodegenerative disease, resulting in progressive problems in language and/or behaviour and is often diagnosed before 65 years of age. Ubiquitin positive protein aggregates in the brain are among the key pathologic hallmarks of frontotemporal lobar degeneration (FTLD) postmortem. The TANK-binding kinase 1 gene (TBK1) is on the list of genes that can contribute to the development of FTD as well as the related neurodegenerative disease amyotrophic lateral sclerosis (ALS).},\n\tlanguage = {en},\n\turldate = {2021-12-02},\n\tjournal = {Journal of Neurology},\n\tauthor = {Khoshnood, Behzad and Ullgren, Abbe and Laffita-Mesa, Jose and Öijerstedt, Linn and Patra, Kalicharan and Nennesmo, Inger and Graff, Caroline},\n\tmonth = nov,\n\tyear = {2021},\n\tkeywords = {Alamut},\n}\n\n

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\n \n\n \n \n \n \n \n \n Returning actionable genomic results in a research biobank: Analytic validity, clinical implementation, and resource utilization.\n \n \n \n \n\n\n \n Blout Zawatsky, C. L.; Shah, N.; Machini, K.; Perez, E.; Christensen, K. D.; Zouk, H.; Steeves, M.; Koch, C.; Uveges, M.; Shea, J.; Gold, N.; Krier, J.; Boutin, N.; Mahanta, L.; Rehm, H. L.; Weiss, S. T.; Karlson, E. W.; Smoller, J. W.; Lebo, M. S.; and Green, R. C.\n\n\n \n\n\n\n The American Journal of Human Genetics. November 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Returning$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{blout_zawatsky_returning_2021,\n\ttitle = {Returning actionable genomic results in a research biobank: {Analytic} validity, clinical implementation, and resource utilization},\n\tissn = {0002-9297},\n\tshorttitle = {Returning actionable genomic results in a research biobank},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0002929721003827},\n\tdoi = {10.1016/j.ajhg.2021.10.005},\n\tabstract = {Over 100 million research participants around the world have had research array-based genotyping (GT) or genome sequencing (GS), but only a small fraction of these have been offered return of actionable genomic findings (gRoR). Between 2017 and 2021, we analyzed genomic results from 36,417 participants in the Mass General Brigham Biobank and offered to confirm and return pathogenic and likely pathogenic variants (PLPVs) in 59 genes. Variant verification prior to participant recontact revealed that GT falsely identified PLPVs in 44.9\\% of samples, and GT failed to identify 72.0\\% of PLPVs detected in a subset of samples that were also sequenced. GT and GS detected verified PLPVs in 1\\% and 2.5\\% of the cohort, respectively. Of 256 participants who were alerted that they carried actionable PLPVs, 37.5\\% actively or passively declined further disclosure. 76.3\\% of those carrying PLPVs were unaware that they were carrying the variant, and over half of those met published professional criteria for genetic testing but had never been tested. This gRoR protocol cost approximately \\$129,000 USD per year in laboratory testing and research staff support, representing \\$14 per participant whose DNA was analyzed or \\$3,224 per participant in whom a PLPV was confirmed and disclosed. These data provide logistical details around gRoR that could help other investigators planning to return genomic results.},\n\tlanguage = {en},\n\turldate = {2021-12-02},\n\tjournal = {The American Journal of Human Genetics},\n\tauthor = {Blout Zawatsky, Carrie L. and Shah, Nidhi and Machini, Kalotina and Perez, Emma and Christensen, Kurt D. and Zouk, Hana and Steeves, Marcie and Koch, Christopher and Uveges, Melissa and Shea, Janelle and Gold, Nina and Krier, Joel and Boutin, Natalie and Mahanta, Lisa and Rehm, Heidi L. and Weiss, Scott T. and Karlson, Elizabeth W. and Smoller, Jordan W. and Lebo, Matthew S. and Green, Robert C.},\n\tmonth = nov,\n\tyear = {2021},\n\tkeywords = {Alamut, biobank, genetic, genomic, research},\n}\n\n

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\n \n\n \n \n \n \n \n \n Clinical evolution, genetic landscape and trajectories of clonal hematopoiesis in SAMD9/SAMD9L syndromes.\n \n \n \n \n\n\n \n Sahoo, S. S.; Pastor, V. B.; Goodings, C.; Voss, R. K.; Kozyra, E. J.; Szvetnik, A.; Noellke, P.; Dworzak, M.; Starý, J.; Locatelli, F.; Masetti, R.; Schmugge, M.; De Moerloose, B.; Catala, A.; Kállay, K.; Turkiewicz, D.; Hasle, H.; Buechner, J.; Jahnukainen, K.; Ussowicz, M.; Polychronopoulou, S.; Smith, O. P.; Fabri, O.; Barzilai, S.; de Haas, V.; Baumann, I.; Schwarz-Furlan, S.; Niewisch, M. R.; Sauer, M. G.; Burkhardt, B.; Lang, P.; Bader, P.; Beier, R.; Müller, I.; Albert, M. H.; Meisel, R.; Schulz, A.; Cario, G.; Panda, P. K.; Wehrle, J.; Hirabayashi, S.; Derecka, M.; Durruthy-Durruthy, R.; Göhring, G.; Yoshimi-Noellke, A.; Ku, M.; Lebrecht, D.; Erlacher, M.; Flotho, C.; Strahm, B.; Niemeyer, C. M.; and Wlodarski, M. W.\n\n\n \n\n\n\n Nature Medicine, 27(10): 1806–1817. October 2021.\n Bandiera_abtest: a Cg_type: Nature Research Journals Number: 10 Primary_atype: Research Publisher: Nature Publishing Group Subject_term: Genetics research;Genome evolution Subject_term_id: genetics-research;genome-evolution\n\n\n\n
\n\n\n\n \n \n $\"Clinical$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{sahoo_clinical_2021,\n\ttitle = {Clinical evolution, genetic landscape and trajectories of clonal hematopoiesis in {SAMD9}/{SAMD9L} syndromes},\n\tvolume = {27},\n\tcopyright = {2021 The Author(s), under exclusive licence to Springer Nature America, Inc.},\n\tissn = {1546-170X},\n\turl = {https://www.nature.com/articles/s41591-021-01511-6},\n\tdoi = {10.1038/s41591-021-01511-6},\n\tabstract = {Germline SAMD9 and SAMD9L mutations (SAMD9/9Lmut) predispose to myelodysplastic syndromes (MDS) with propensity for somatic rescue. In this study, we investigated a clinically annotated pediatric MDS cohort (n = 669) to define the prevalence, genetic landscape, phenotype, therapy outcome and clonal architecture of SAMD9/9L syndromes. In consecutively diagnosed MDS, germline SAMD9/9Lmut accounted for 8\\% and were mutually exclusive with GATA2 mutations present in 7\\% of the cohort. Among SAMD9/9Lmut cases, refractory cytopenia was the most prevalent MDS subtype (90\\%); acquired monosomy 7 was present in 38\\%; constitutional abnormalities were noted in 57\\%; and immune dysfunction was present in 28\\%. The clinical outcome was independent of germline mutations. In total, 67 patients had 58 distinct germline SAMD9/9Lmut clustering to protein middle regions. Despite inconclusive in silico prediction, 94\\% of SAMD9/9Lmut suppressed HEK293 cell growth, and mutations expressed in CD34+ cells induced overt cell death. Furthermore, we found that 61\\% of SAMD9/9Lmut patients underwent somatic genetic rescue (SGR) resulting in clonal hematopoiesis, of which 95\\% was maladaptive (monosomy 7 ± cancer mutations), and 51\\% had adaptive nature (revertant UPD7q, somatic SAMD9/9Lmut). Finally, bone marrow single-cell DNA sequencing revealed multiple competing SGR events in individual patients. Our findings demonstrate that SGR is common in SAMD9/9Lmut MDS and exemplify the exceptional plasticity of hematopoiesis in children.},\n\tlanguage = {en},\n\tnumber = {10},\n\turldate = {2021-11-30},\n\tjournal = {Nature Medicine},\n\tauthor = {Sahoo, Sushree S. and Pastor, Victor B. and Goodings, Charnise and Voss, Rebecca K. and Kozyra, Emilia J. and Szvetnik, Amina and Noellke, Peter and Dworzak, Michael and Starý, Jan and Locatelli, Franco and Masetti, Riccardo and Schmugge, Markus and De Moerloose, Barbara and Catala, Albert and Kállay, Krisztián and Turkiewicz, Dominik and Hasle, Henrik and Buechner, Jochen and Jahnukainen, Kirsi and Ussowicz, Marek and Polychronopoulou, Sophia and Smith, Owen P. and Fabri, Oksana and Barzilai, Shlomit and de Haas, Valerie and Baumann, Irith and Schwarz-Furlan, Stephan and Niewisch, Marena R. and Sauer, Martin G. and Burkhardt, Birgit and Lang, Peter and Bader, Peter and Beier, Rita and Müller, Ingo and Albert, Michael H. and Meisel, Roland and Schulz, Ansgar and Cario, Gunnar and Panda, Pritam K. and Wehrle, Julius and Hirabayashi, Shinsuke and Derecka, Marta and Durruthy-Durruthy, Robert and Göhring, Gudrun and Yoshimi-Noellke, Ayami and Ku, Manching and Lebrecht, Dirk and Erlacher, Miriam and Flotho, Christian and Strahm, Brigitte and Niemeyer, Charlotte M. and Wlodarski, Marcin W.},\n\tmonth = oct,\n\tyear = {2021},\n\tnote = {Bandiera\\_abtest: a\nCg\\_type: Nature Research Journals\nNumber: 10\nPrimary\\_atype: Research\nPublisher: Nature Publishing Group\nSubject\\_term: Genetics research;Genome evolution\nSubject\\_term\\_id: genetics-research;genome-evolution},\n\tkeywords = {Alamut, Custom Panel, Genetics research, Genome evolution},\n\tpages = {1806--1817},\n}\n\n

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\n \n\n \n \n \n \n \n \n Whole exome sequencing identifies monogenic forms of nephritis in a previously unsolved cohort of children with steroid-resistant nephrotic syndrome and hematuria.\n \n \n \n \n\n\n \n Xiao, H.; and Hildebrandt, F.\n\n\n \n\n\n\n Pediatric Nephrology. November 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Whole$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 8 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{xiao_whole_2021,\n\ttitle = {Whole exome sequencing identifies monogenic forms of nephritis in a previously unsolved cohort of children with steroid-resistant nephrotic syndrome and hematuria},\n\tissn = {1432-198X},\n\turl = {https://doi.org/10.1007/s00467-021-05312-4},\n\tdoi = {10.1007/s00467-021-05312-4},\n\tabstract = {Alport syndrome (AS), atypical hemolytic-uremic syndrome (aHUS), and fibronectin-glomerulopathy (FG) are rare forms of glomerular diseases that manifest in a combination of proteinuria, hematuria, and hypertension, referred to as nephritic syndrome. Due to phenotypic overlays, steroid-resistant nephrotic syndrome (SRNS) and nephritic syndrome have been difficult to discern diagnostically. SRNS is more common than nephritic syndrome and is the second leading cause of childhood-onset CKD. Fourteen monogenic causes of AS, aHUS, and FG and 60 monogenic causes of SRNS have been identified. As whole exome sequencing (WES) allows for unequivocal molecular genetic diagnostics, we hypothesize to be able to identify causative mutations in genes known to cause nephritic syndrome in patient cohorts with a clinical diagnosis of SRNS.},\n\tlanguage = {en},\n\turldate = {2021-11-19},\n\tjournal = {Pediatric Nephrology},\n\tauthor = {Xiao, Hongbo and Hildebrandt, Friedhelm},\n\tmonth = nov,\n\tyear = {2021},\n\tkeywords = {Alamut},\n}\n\n

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\n \n\n \n \n \n \n \n \n Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis Due to CLDN16 Gene Mutations: Novel Findings in Two Cases with Diverse Clinical Features.\n \n \n \n \n\n\n \n Eltan, M.; Yavas Abali, Z.; Turkyilmaz, A.; Gokce, I.; Abali, S.; Alavanda, C.; Arman, A.; Kirkgoz, T.; Guran, T.; Hatun, S.; Bereket, A.; and Turan, S.\n\n\n \n\n\n\n Calcified Tissue International. November 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Familial$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{eltan_familial_2021,\n\ttitle = {Familial {Hypomagnesemia} with {Hypercalciuria} and {Nephrocalcinosis} {Due} to {CLDN16} {Gene} {Mutations}: {Novel} {Findings} in {Two} {Cases} with {Diverse} {Clinical} {Features}},\n\tissn = {1432-0827},\n\tshorttitle = {Familial {Hypomagnesemia} with {Hypercalciuria} and {Nephrocalcinosis} {Due} to {CLDN16} {Gene} {Mutations}},\n\turl = {https://doi.org/10.1007/s00223-021-00928-y},\n\tdoi = {10.1007/s00223-021-00928-y},\n\tabstract = {Biallelic loss of function mutations in the CLDN16 gene cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), and chronic kidney disease. Here we report two cases of FHHNC with diverse clinical presentations and hypercalcemia in one as a novel finding. Pt\\#1 initially presented with urinary tract infection and failure to thrive at 5.5 months of age to another center. Bilateral nephrocalcinosis, hypercalcemia (Ca: 12.2 mg/dl), elevated parathyroid hormone (PTH) level, and hypercalciuria were detected. Persistently elevated PTH with high/normal Ca levels led to subtotal-parathyroidectomy at the age of 2.5. However, PTH levels remained elevated with progressive deterioration in renal function. At 9-year-old, she was referred to us for evaluation of hyperparathyroidism and, hypomagnesemia together with hypercalciuria, elevated PTH with normal Ca levels, and medullary nephrocalcinosis were detected. Compound heterozygosity of CLDN16 variants (c.715G{\\textgreater}A, p.G239R; and novel c.360C{\\textgreater}A, p.C120*) confirmed the diagnosis. Pt\\#2 was a 10-month-old boy, admitted with irritability and urinary crystals. Hypocalcemia, hypophosphatemia, elevated PTH and ALP, low 25(OH)D levels, and radiographic findings of rickets were detected. However, additional findings of hypercalciuria and bilateral nephrocalcinosis were inconsistent with the nutritional rickets. Low/normal serum Mg levels suggested the diagnosis of FHHNC which was confirmed genetically as a homozygous missense (c.602G {\\textgreater} A; p.G201E) variant in CLDN16. Yet, hypocalcemia and hypomagnesemia persisted in spite of treatment. In conclusion, FHHNC may present with diverse clinical features with mild hypomagnesemia leading to secondary hyperparathyroidism with changing Ca levels from low to high. Early and accurate clinical and molecular genetic diagnosis is important for proper management.},\n\tlanguage = {en},\n\turldate = {2021-11-19},\n\tjournal = {Calcified Tissue International},\n\tauthor = {Eltan, Mehmet and Yavas Abali, Zehra and Turkyilmaz, Ayberk and Gokce, Ibrahim and Abali, Saygın and Alavanda, Ceren and Arman, Ahmet and Kirkgoz, Tarik and Guran, Tulay and Hatun, Sukru and Bereket, Abdullah and Turan, Serap},\n\tmonth = nov,\n\tyear = {2021},\n}\n\n

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\n \n\n \n \n \n \n \n \n BRCA Variations Risk Assessment in Breast Cancers Using Different Artificial Intelligence Models.\n \n \n \n \n\n\n \n Senturk, N.; Tuncel, G.; Dogan, B.; Aliyeva, L.; Dundar, M. S.; Ozemri Sag, S.; Mocan, G.; Temel, S. G.; Dundar, M.; and Ergoren, M. C.\n\n\n \n\n\n\n Genes, 12(11): 1774. November 2021.\n Number: 11 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"BRCA$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{senturk_brca_2021,\n\ttitle = {{BRCA} {Variations} {Risk} {Assessment} in {Breast} {Cancers} {Using} {Different} {Artificial} {Intelligence} {Models}},\n\tvolume = {12},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\turl = {https://www.mdpi.com/2073-4425/12/11/1774},\n\tdoi = {10.3390/genes12111774},\n\tabstract = {Artificial intelligence provides modelling on machines by simulating the human brain using learning and decision-making abilities. Early diagnosis is highly effective in reducing mortality in cancer. This study aimed to combine cancer-associated risk factors including genetic variations and design an artificial intelligence system for risk assessment. Data from a total of 268 breast cancer patients have been analysed for 16 different risk factors including genetic variant classifications. In total, 61 BRCA1, 128 BRCA2 and 11 both BRCA1 and BRCA2 genes associated breast cancer patients’ data were used to train the system using Mamdani’s Fuzzy Inference Method and Feed-Forward Neural Network Method as the model softwares on MATLAB. Sixteen different tests were performed on twelve different subjects who had not been introduced to the system before. The rates for neural network were 99.9\\% for training success, 99.6\\% for validation success and 99.7\\% for test success. Despite neural network’s overall success was slightly higher than fuzzy logic accuracy, the results from developed systems were similar (99.9\\% and 95.5\\%, respectively). The developed models make predictions from a wider perspective using more risk factors including genetic variation data compared with similar studies in the literature. Overall, this artificial intelligence models present promising results for BRCA variations’ risk assessment in breast cancers as well as a unique tool for personalized medicine software.},\n\tlanguage = {en},\n\tnumber = {11},\n\turldate = {2021-11-19},\n\tjournal = {Genes},\n\tauthor = {Senturk, Niyazi and Tuncel, Gulten and Dogan, Berkcan and Aliyeva, Lamiya and Dundar, Mehmet Sait and Ozemri Sag, Sebnem and Mocan, Gamze and Temel, Sehime Gulsun and Dundar, Munis and Ergoren, Mahmut Cerkez},\n\tmonth = nov,\n\tyear = {2021},\n\tnote = {Number: 11\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {BRCA1, BRCA2, SOPHiA DDM, artificial intelligence, breast cancer, translational fuzzy logic, variation},\n\tpages = {1774},\n}\n\n

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\n \n\n \n \n \n \n \n \n A Novel Homozygous Mutation in the MYO5B Gene Associated With Normal-Gamma-Glutamyl Transferase Progressive Familial Intrahepatic Cholestasis.\n \n \n \n \n\n\n \n Aksu, N. U.; Görükmez, O.; Görükmez, Ö.; and Uncuoğlu, A.\n\n\n \n\n\n\n Cureus, 13(11). November 2021.\n Publisher: Cureus\n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{aksu_novel_2021,\n\ttitle = {A {Novel} {Homozygous} {Mutation} in the {MYO5B} {Gene} {Associated} {With} {Normal}-{Gamma}-{Glutamyl} {Transferase} {Progressive} {Familial} {Intrahepatic} {Cholestasis}},\n\tvolume = {13},\n\tissn = {2168-8184},\n\turl = {https://www.cureus.com/articles/72832-a-novel-homozygous-mutation-in-the-myo5b-gene-associated-with-normal-gamma-glutamyl-transferase-progressive-familial-intrahepatic-cholestasis},\n\tdoi = {10.7759/cureus.19326},\n\tabstract = {The genetic defect of MYO5B is usually associated with microvillus inclusion disease (MVID). MYO5B mutations are one of the rare causes of progressive familial intrahepatic cholestasis (PFIC) with normal/low gamma-glutamyl transferase (GGT). In this report, we discuss the case of a nine-month-old girl with low-GGT cholestasis whose next-generation sequencing (NGS) showed a homozygous splicing variation (c.3045+3A\\&gt;T) on the MYO5B (NM\\_001080467) gene, which was a novel mutation. We identified that this mutation had a disease-causing effect in silico analysis.},\n\tlanguage = {en},\n\tnumber = {11},\n\turldate = {2021-11-12},\n\tjournal = {Cureus},\n\tauthor = {Aksu, Nihal Uyar and Görükmez, Orhan and Görükmez, Özlem and Uncuoğlu, Ayşen},\n\tmonth = nov,\n\tyear = {2021},\n\tnote = {Publisher: Cureus},\n\tkeywords = {CES},\n}\n\n

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\n \n\n \n \n \n \n \n \n Liquid biopsy: Novel perspectives on the importance and spectrum of \\textlessem\\textgreaterPIK3CA, PTEN\\textless/em\\textgreater and \\textlessem\\textgreaterRET\\textless/em\\textgreater mutations in solid tumors.\n \n \n \n \n\n\n \n Sahin, I.; Saat, H.; Aksoy, S.; Dizdar, O.; Erdem, H. B.; and Bahsi, T.\n\n\n \n\n\n\n Molecular and Clinical Oncology, 16(1): 1–7. November 2021.\n Publisher: Spandidos Publications\n\n\n\n
\n\n\n\n \n \n $\"Liquid$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{sahin_liquid_2021,\n\ttitle = {Liquid biopsy: {Novel} perspectives on the importance and spectrum of {\\textless}em{\\textgreater}{PIK3CA}, {PTEN}{\\textless}/em{\\textgreater} and {\\textless}em{\\textgreater}{RET}{\\textless}/em{\\textgreater} mutations in solid tumors},\n\tvolume = {16},\n\tissn = {2049-9450},\n\tshorttitle = {Liquid biopsy},\n\turl = {https://www.spandidos-publications.com/10.3892/mco.2021.2434},\n\tdoi = {10.3892/mco.2021.2434},\n\tabstract = {Many people die from lung and breast cancer. Consequently, both physicians and researchers strive to provide reliable monitoring for disease, diagnosis and prognosis as well as resistance prediction. In the present study, a comprehensive liquid biopsy panel was performed on 474 patients to examine the importance and spectrum of recurrent somatic cancer mutations. Most patients visited the clinic with a diagnosis of advanced resistant cancer. The patients underwent a comprehensive liquid biopsy panel. Patients were divided into four groups based on cancer type as follows: Lung (n=379, 79.9\\%), breast (n=72, 15.2\\%), gastrointestinal (n=11, 2.3\\%) and other (n=12, 2.5\\%). Tier I‑II‑III classified variants were included in the study. The mean age was 60 years, with a range of 20‑86 years. There were notably more male (n=272, 57.4\\%) than female patients (n=202, 42.6\\%). The most commonly mutated genes were {\\textless}em{\\textgreater}TP53, EGFR, PIK3CA, RET, PTEN, MET, ATM {\\textless}/em{\\textgreater}and{\\textless}em{\\textgreater} KRAS{\\textless}/em{\\textgreater}. The most common mutations were ‘{\\textless}em{\\textgreater}PIK3CA{\\textless}/em{\\textgreater}, c.3140A\\&gt;G, p.His1047Arg’, ‘{\\textless}em{\\textgreater}RET{\\textless}/em{\\textgreater}, c.2324delinsGAC, p.Glu775Glyfs*6’, ‘{\\textless}em{\\textgreater}TP53{\\textless}/em{\\textgreater}, c.217G\\&gt;C, p.Val73Leu’, ‘{\\textless}em{\\textgreater}EGFR{\\textless}/em{\\textgreater}, c.2155G\\&gt;A, p.Gly719Ser’, ‘{\\textless}em{\\textgreater}PIK3CA{\\textless}/em{\\textgreater}, c.1624G\\&gt;A, p.Glu542Lys’, ‘{\\textless}em{\\textgreater}PTEN{\\textless}/em{\\textgreater}, c.397G\\&gt;A, p.Val133Ile’ and ‘{\\textless}em{\\textgreater}EGFR{\\textless}/em{\\textgreater}, c.2235\\_2249del, p.Glu746\\_Ala750del’. The {\\textless}em{\\textgreater}PIK3CA{\\textless}/em{\\textgreater}, {\\textless}em{\\textgreater}PTEN{\\textless}/em{\\textgreater} and {\\textless}em{\\textgreater}RET{\\textless}/em{\\textgreater} variants showed a higher incidence in the breast and lung groups compared with other groups. To the best of our knowledge, the present study is the first to concentrate on {\\textless}em{\\textgreater}PIK3CA{\\textless}/em{\\textgreater}, {\\textless}em{\\textgreater}PTEN{\\textless}/em{\\textgreater} and {\\textless}em{\\textgreater}RET{\\textless}/em{\\textgreater} mutations in the context of breast and lung adenocarcinoma and to evaluate both genetic variability and the effect of treatment. The present results showed that patients with solid tumors, particularly lung and breast cancer, may benefit from {\\textless}em{\\textgreater}PIK3CA{\\textless}/em{\\textgreater}, {\\textless}em{\\textgreater}PTEN{\\textless}/em{\\textgreater} and {\\textless}em{\\textgreater}RET{\\textless}/em{\\textgreater} sequencing to assess clinical characteristics and prognosis. Discoveries regarding the gene structure and mechanisms of {\\textless}em{\\textgreater}PIK3CA{\\textless}/em{\\textgreater}, {\\textless}em{\\textgreater}PTEN{\\textless}/em{\\textgreater} and {\\textless}em{\\textgreater}RET{\\textless}/em{\\textgreater} may inform more clinically meaningful therapeutic approaches for patients with cancer and serve an essential role in improving individual risk prediction, therapy and prognosis.},\n\tnumber = {1},\n\turldate = {2021-11-12},\n\tjournal = {Molecular and Clinical Oncology},\n\tauthor = {Sahin, Ibrahim and Saat, Hanife and Aksoy, Sercan and Dizdar, Omer and Erdem, Haktan Bagis and Bahsi, Taha},\n\tmonth = nov,\n\tyear = {2021},\n\tnote = {Publisher: Spandidos Publications},\n\tkeywords = {oncology solution},\n\tpages = {1--7},\n}\n\n

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\n Many people die from lung and breast cancer. Consequently, both physicians and researchers strive to provide reliable monitoring for disease, diagnosis and prognosis as well as resistance prediction. In the present study, a comprehensive liquid biopsy panel was performed on 474 patients to examine the importance and spectrum of recurrent somatic cancer mutations. Most patients visited the clinic with a diagnosis of advanced resistant cancer. The patients underwent a comprehensive liquid biopsy panel. Patients were divided into four groups based on cancer type as follows: Lung (n=379, 79.9%), breast (n=72, 15.2%), gastrointestinal (n=11, 2.3%) and other (n=12, 2.5%). Tier I‑II‑III classified variants were included in the study. The mean age was 60 years, with a range of 20‑86 years. There were notably more male (n=272, 57.4%) than female patients (n=202, 42.6%). The most commonly mutated genes were \\textlessem\\textgreaterTP53, EGFR, PIK3CA, RET, PTEN, MET, ATM \\textless/em\\textgreaterand\\textlessem\\textgreater KRAS\\textless/em\\textgreater. The most common mutations were ‘\\textlessem\\textgreaterPIK3CA\\textless/em\\textgreater, c.3140A>G, p.His1047Arg’, ‘\\textlessem\\textgreaterRET\\textless/em\\textgreater, c.2324delinsGAC, p.Glu775Glyfs*6’, ‘\\textlessem\\textgreaterTP53\\textless/em\\textgreater, c.217G>C, p.Val73Leu’, ‘\\textlessem\\textgreaterEGFR\\textless/em\\textgreater, c.2155G>A, p.Gly719Ser’, ‘\\textlessem\\textgreaterPIK3CA\\textless/em\\textgreater, c.1624G>A, p.Glu542Lys’, ‘\\textlessem\\textgreaterPTEN\\textless/em\\textgreater, c.397G>A, p.Val133Ile’ and ‘\\textlessem\\textgreaterEGFR\\textless/em\\textgreater, c.2235_2249del, p.Glu746_Ala750del’. The \\textlessem\\textgreaterPIK3CA\\textless/em\\textgreater, \\textlessem\\textgreaterPTEN\\textless/em\\textgreater and \\textlessem\\textgreaterRET\\textless/em\\textgreater variants showed a higher incidence in the breast and lung groups compared with other groups. To the best of our knowledge, the present study is the first to concentrate on \\textlessem\\textgreaterPIK3CA\\textless/em\\textgreater, \\textlessem\\textgreaterPTEN\\textless/em\\textgreater and \\textlessem\\textgreaterRET\\textless/em\\textgreater mutations in the context of breast and lung adenocarcinoma and to evaluate both genetic variability and the effect of treatment. The present results showed that patients with solid tumors, particularly lung and breast cancer, may benefit from \\textlessem\\textgreaterPIK3CA\\textless/em\\textgreater, \\textlessem\\textgreaterPTEN\\textless/em\\textgreater and \\textlessem\\textgreaterRET\\textless/em\\textgreater sequencing to assess clinical characteristics and prognosis. Discoveries regarding the gene structure and mechanisms of \\textlessem\\textgreaterPIK3CA\\textless/em\\textgreater, \\textlessem\\textgreaterPTEN\\textless/em\\textgreater and \\textlessem\\textgreaterRET\\textless/em\\textgreater may inform more clinically meaningful therapeutic approaches for patients with cancer and serve an essential role in improving individual risk prediction, therapy and prognosis.\n

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\n \n\n \n \n \n \n \n \n Mutational Hotspot in the SARS-CoV-2 Spike Protein N-Terminal Domain Conferring Immune Escape Potential.\n \n \n \n \n\n\n \n Kubik, S.; Arrigo, N.; Bonet, J.; and Xu, Z.\n\n\n \n\n\n\n Viruses, 13(11): 2114. October 2021.\n Number: 11 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Mutational$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 10 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{kubik_mutational_2021,\n\ttitle = {Mutational {Hotspot} in the {SARS}-{CoV}-2 {Spike} {Protein} {N}-{Terminal} {Domain} {Conferring} {Immune} {Escape} {Potential}},\n\tvolume = {13},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\turl = {https://www.mdpi.com/1999-4915/13/11/2114},\n\tdoi = {10.3390/v13112114},\n\tabstract = {Global efforts are being made to monitor the evolution of SARS-CoV-2, aiming for early identification of genotypes providing increased infectivity or virulence. However, viral lineage-focused tracking might fail in early detection of advantageous mutations emerging independently across phylogenies. Here, the emergence patterns of Spike mutations were investigated in sequences deposited in local and global databases to identify mutational hotspots across phylogenies and we evaluated their impact on SARS-CoV-2 evolution. We found a striking increase in the frequency of recruitment of diverse substitutions at a critical residue (W152), positioned in the N-terminal domain (NTD) of the Spike protein, observed repeatedly across independent phylogenetic and geographical contexts. These mutations might have an impact on the evasion of neutralizing antibodies. Finally, we found that NTD is a region exhibiting particularly high frequency of mutation recruitments, suggesting an evolutionary path in which the virus maintains optimal efficiency of ACE2 binding combined with the flexibility facilitating the immune escape. We conclude that adaptive mutations, frequently present outside of the receptor-binding domain, can emerge in virtually any SARS-CoV-2 lineage and at any geographical location. Therefore, surveillance should not be restricted to monitoring defined lineages alone.},\n\tlanguage = {en},\n\tnumber = {11},\n\turldate = {2021-11-12},\n\tjournal = {Viruses},\n\tauthor = {Kubik, Slawomir and Arrigo, Nils and Bonet, Jaume and Xu, Zhenyu},\n\tmonth = oct,\n\tyear = {2021},\n\tnote = {Number: 11\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {SARS-CoV-2 genome, W152, coronavirus, immune escape, neutralizing antibody, spike NTD, viral evolution},\n\tpages = {2114},\n}\n\n

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\n \n\n \n \n \n \n \n \n Secondary basophilic leukemia in Ph-negative myeloid neoplasms: A distinct subset with poor prognosis.\n \n \n \n \n\n\n \n Berger, D.; Bauer, K.; Kornauth, C.; Gamperl, S.; Stefanzl, G.; Smiljkovic, D.; Sillaber, C.; Bettelheim, P.; Knöbl, P.; Schiefer, A.; Greiner, G.; Thalhammer, R.; Hoermann, G.; Schwarzinger, I.; Staber, P. B.; Sperr, W. R.; and Valent, P.\n\n\n \n\n\n\n Neoplasia, 23(12): 1183–1191. October 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Secondary$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{berger_secondary_2021,\n\ttitle = {Secondary basophilic leukemia in {Ph}-negative myeloid neoplasms: {A} distinct subset with poor prognosis},\n\tvolume = {23},\n\tissn = {1476-5586},\n\tshorttitle = {Secondary basophilic leukemia in {Ph}-negative myeloid neoplasms},\n\turl = {https://www.sciencedirect.com/science/article/pii/S1476558621000853},\n\tdoi = {10.1016/j.neo.2021.09.010},\n\tabstract = {During progression of myeloid neoplasms, the basophil compartment may expand substantially and in some of these patients, a basophilic leukemia is diagnosed. In patients with Ph-chromosome+ chronic myeloid leukemia, acceleration of disease is typically accompanied by marked basophilia. In other myeloid neoplasms, secondary leukemic expansion of basophils is rarely seen. We report on 5 patients who suffered from a myelodysplastic syndrome, myeloproliferative neoplasm, or acute leukemia and developed a massive expansion of basophils during disease progression. In 4 of 5 patients, peripheral blood basophil counts reached 40\\%, and the diagnosis “secondary basophilic leukemia” was established. As assessed by flow cytometry, neoplastic basophils expressed CD9, CD18, CD25, CD33, CD63, PD-L1, CD123, and CLL-1. In addition, basophils were found to display BB1 (basogranulin), 2D7, tryptase and KIT. In 4 of 5 patients the disease progressed quickly and treatment with azacitidine was started. However, azacitidine did not induce major clinical responses, and all patients died from progressive disease within 3 Y. In in vitro experiments, the patients´ cells and the basophilic leukemia cell line KU812 showed variable responses to targeted drugs, including azacitidine, venetoclax, hydroxyurea, and cytarabine. A combination of venetoclax and azacitidine induced cooperative antineoplastic effects in these cells. Together, secondary basophilic leukemia has a poor prognosis and monotherapy with azacitidine is not sufficient to keep the disease under control for longer time-periods. Whether drug combination, such as venetoclax+azacitidine, can induce better outcomes in these patients remains to be determined in future clinical studies.},\n\tlanguage = {en},\n\tnumber = {12},\n\turldate = {2021-11-11},\n\tjournal = {Neoplasia},\n\tauthor = {Berger, Daniela and Bauer, Karin and Kornauth, Christoph and Gamperl, Susanne and Stefanzl, Gabriele and Smiljkovic, Dubravka and Sillaber, Christian and Bettelheim, Peter and Knöbl, Paul and Schiefer, Ana-Iris and Greiner, Georg and Thalhammer, Renate and Hoermann, Gregor and Schwarzinger, Ilse and Staber, Philipp B. and Sperr, Wolfgang R. and Valent, Peter},\n\tmonth = oct,\n\tyear = {2021},\n\tkeywords = {Azacitidine, Basophilic leukemia, Basophils, IgE receptor, MYS, Venetoclax},\n\tpages = {1183--1191},\n}\n\n

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\n \n\n \n \n \n \n \n \n Divergent leukaemia subclones as cellular models for testing vulnerabilities associated with gains in chromosomes 7, 8 or 18.\n \n \n \n \n\n\n \n Maher, M.; Diesch, J.; Le Pannérer, M.; Cabezón, M.; Mallo, M.; Vergara, S.; Méndez López, A.; Mesa Tudel, A.; Solé, F.; Sorigue, M.; Zamora, L.; Granada, I.; and Buschbeck, M.\n\n\n \n\n\n\n Scientific Reports, 11(1): 21145. October 2021.\n Bandiera_abtest: a Cc_license_type: cc_by Cg_type: Nature Research Journals Number: 1 Primary_atype: Research Publisher: Nature Publishing Group Subject_term: Acute myeloid leukaemia;Biomarkers;Cancer genetics;Haematological cancer;Translational research Subject_term_id: acute-myeloid-leukaemia;biomarkers;cancer-genetics;haematological-cancer;translational-research\n\n\n\n
\n\n\n\n \n \n $\"Divergent$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{maher_divergent_2021,\n\ttitle = {Divergent leukaemia subclones as cellular models for testing vulnerabilities associated with gains in chromosomes 7, 8 or 18},\n\tvolume = {11},\n\tcopyright = {2021 The Author(s)},\n\tissn = {2045-2322},\n\turl = {https://www.nature.com/articles/s41598-021-00623-w},\n\tdoi = {10.1038/s41598-021-00623-w},\n\tabstract = {Haematopoietic malignancies are frequently characterized by karyotypic abnormalities. The development of targeted drugs has been pioneered with compounds against gene products of fusion genes caused by chromosomal translocations. While polysomies are equally frequent as translocations, for many of them we are lacking therapeutic approaches aimed at synthetic lethality. Here, we report two new cell lines, named MBU-7 and MBU-8, that differ in complete trisomy of chromosome18, a partial trisomy of chromosome 7 and a tetrasomy of the p-arm of chromosome 8, but otherwise share the same mutational pattern and complex karyotype. Both cell lines are divergent clones of U-937 cells and have the morphology and immunoprofile of monocytic cells. The distinct karyotypic differences between MBU-7 and MBU-8 are associated with a difference in the specific response to nucleoside analogues. Taken together, we propose the MBU-7 and MBU-8 cell lines described here as suitable in vitro models for screening and testing vulnerabilities that are associated with the disease-relevant polysomies of chromosome 7, 8 and 18.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2021-11-11},\n\tjournal = {Scientific Reports},\n\tauthor = {Maher, Michael and Diesch, Jeannine and Le Pannérer, Marguerite-Marie and Cabezón, Marta and Mallo, Mar and Vergara, Sara and Méndez López, Aleix and Mesa Tudel, Alba and Solé, Francesc and Sorigue, Marc and Zamora, Lurdes and Granada, Isabel and Buschbeck, Marcus},\n\tmonth = oct,\n\tyear = {2021},\n\tnote = {Bandiera\\_abtest: a\nCc\\_license\\_type: cc\\_by\nCg\\_type: Nature Research Journals\nNumber: 1\nPrimary\\_atype: Research\nPublisher: Nature Publishing Group\nSubject\\_term: Acute myeloid leukaemia;Biomarkers;Cancer genetics;Haematological cancer;Translational research\nSubject\\_term\\_id: acute-myeloid-leukaemia;biomarkers;cancer-genetics;haematological-cancer;translational-research},\n\tkeywords = {Acute myeloid leukaemia, Biomarkers, Cancer genetics, Haematological cancer, MYS, SOPHiA DDM, Translational research},\n\tpages = {21145},\n}\n\n

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\n \n\n \n \n \n \n \n \n Validation of amplicon-based next generation sequencing panel for second-tier test in newborn screening for inborn errors of metabolism.\n \n \n \n \n\n\n \n Tsang, K. Y.; Chan, T. C. H.; Yeung, M. C. W.; Wong, T. K.; Lau, W. T.; and Mak, C. M.\n\n\n \n\n\n\n Journal of Laboratory Medicine. October 2021.\n Publisher: De Gruyter\n\n\n\n
\n\n\n\n \n \n $\"Validation$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{tsang_validation_2021,\n\ttitle = {Validation of amplicon-based next generation sequencing panel for second-tier test in newborn screening for inborn errors of metabolism},\n\tissn = {2567-9449},\n\turl = {https://www.degruyter.com/document/doi/10.1515/labmed-2021-0115/html},\n\tdoi = {10.1515/labmed-2021-0115},\n\tabstract = {Objectives Next generation sequencing (NGS) technology has allowed cost-effective massive parallel DNA sequencing. To evaluate the utility of NGS for newborn screening (NBS) of inborn errors of metabolism (IEM), a custom panel was designed to target 87 disease-related genes. The pilot study was primarily proposed for second-tier testing under the NBSIEM program in Hong Kong. Methods The validation of the panel was performed with two reference genomes and an external quality assurance (EQA) sample. Sequencing libraries were synthesized with amplicon-based approach. The libraries were pooled, spiked-in with 2\\% PhiX DNA as technical control, for 16-plex sequencing runs. Sequenced reads were analyzed using a commercially available pipeline. Results The average target region coverage was 208× and the fraction of region with target depth ≥20× was 95.7\\%, with a sensitivity of 91.2\\%. There were 85 out of 87 genes with acceptable coverage, and EQA result was satisfactory. The turnaround time from DNA extraction to completion of variant calling and quality control (QC) procedures was 2.5 days. Conclusions The NGS approach with the amplicon-based panel has been validated for analytical performance and is suitable for second-tier NBSIEM test.},\n\tlanguage = {en},\n\turldate = {2021-11-01},\n\tjournal = {Journal of Laboratory Medicine},\n\tauthor = {Tsang, Kwok Yeung and Chan, Toby Chun Hei and Yeung, Matthew Chun Wing and Wong, Tsz Ki and Lau, Wan Ting and Mak, Chloe Miu},\n\tmonth = oct,\n\tyear = {2021},\n\tnote = {Publisher: De Gruyter},\n\tkeywords = {Alamut, dried blood spot (DBS), inborn errors of metabolism (IEM), newborn screening (NBS), next generation sequencing (NGS), second-tier test},\n}\n\n

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\n \n\n \n \n \n \n \n \n Last nucleotide substitutions of COL4A5 exons cause aberrant splicing.\n \n \n \n \n\n\n \n Aoto, Y.; Horinouchi, T.; Yamamura, T.; Kondo, A.; Nagai, S.; Ishiko, S.; Okada, E.; Rossanti, R.; Sakakibara, N.; Nagano, C.; Awano, H.; Nagase, H.; Shima, Y.; Nakanishi, K.; Matsuo, M.; Iijima, K.; and Nozu, K.\n\n\n \n\n\n\n Kidney International Reports. October 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Last$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{aoto_last_2021,\n\ttitle = {Last nucleotide substitutions of {COL4A5} exons cause aberrant splicing},\n\tissn = {2468-0249},\n\turl = {https://www.sciencedirect.com/science/article/pii/S2468024921014716},\n\tdoi = {10.1016/j.ekir.2021.10.012},\n\tabstract = {Background\nCOL4A5 is a causative gene of X-linked Alport syndrome (XLAS). Male XLAS patients with nonsense variants show the most severe phenotypes of early-onset end-stage kidney disease; splicing variants show middle phenotypes; and missense variants show the mildest phenotypes. Therefore, genotyping for male XLAS patients can be used to predict kidney prognosis. Single-base substitutions at the last nucleotide position in each exon are known to affect splicing patterns, and could be splicing variants. However, in XLAS, these variants are generally considered to be missense variants, without conducting a transcript analysis, which underestimates some patients as mild phenotypes. This study aimed to investigate whether single-base substitutions at the last nucleotide position of COL4A5 exons cause aberrant splicing.\nMethods\nIn total, 20 variants were found in the Human Gene Mutation Database (n = 14) and our cohort (n = 6). We performed functional splicing assays using a hybrid minigene analysis and in vivo transcript analyses of patients’ samples when available. Then, we investigated genotype–phenotype correlations for patients with splicing variants detected in this study by comparing data from our previous studies.\nResults\nAmong 20 variants, 17 (85\\%) caused aberrant splicing. Male patients with splicing variants showed more severe phenotypes when compared to missense variants. Findings from the in vivo analyses for three variants were identical to those from the minigene assay.\nConclusion\nOur study revealed that most single-base substitutions at the last nucleotide position of COL4A5 exons result in splicing variants, rather than missense variants, thereby leading to more severe phenotypes.},\n\tlanguage = {en},\n\turldate = {2021-11-01},\n\tjournal = {Kidney International Reports},\n\tauthor = {Aoto, Yuya and Horinouchi, Tomoko and Yamamura, Tomohiko and Kondo, Atsushi and Nagai, Sadayuki and Ishiko, Shinya and Okada, Eri and Rossanti, Rini and Sakakibara, Nana and Nagano, China and Awano, Hiroyuki and Nagase, Hiroaki and Shima, Yuko and Nakanishi, Koichi and Matsuo, Masafumi and Iijima, Kazumoto and Nozu, Kandai},\n\tmonth = oct,\n\tyear = {2021},\n\tkeywords = {Alamut, genotype–phenotype correlation, last nucleotide position, missense variants, single-base substitutions, splicing},\n}\n\n

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\n \n\n \n \n \n \n \n \n An Updated PAH Mutational Spectrum of Phenylketonuria in Mexican Patients Attending a Single Center: Biochemical, Clinical-Genotyping Correlations.\n \n \n \n \n\n\n \n Vela-Amieva, M.; Alcántara-Ortigoza, M. A.; Ibarra-González, I.; González-del Angel, A.; Fernández-Hernández, L.; Guillén-López, S.; López-Mejía, L.; Carrillo-Nieto, R. I.; Belmont-Martínez, L.; and Fernández-Lainez, C.\n\n\n \n\n\n\n Genes, 12(11): 1676. October 2021.\n Number: 11 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"An$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{vela-amieva_updated_2021,\n\ttitle = {An {Updated} {PAH} {Mutational} {Spectrum} of {Phenylketonuria} in {Mexican} {Patients} {Attending} a {Single} {Center}: {Biochemical}, {Clinical}-{Genotyping} {Correlations}},\n\tvolume = {12},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tshorttitle = {An {Updated} {PAH} {Mutational} {Spectrum} of {Phenylketonuria} in {Mexican} {Patients} {Attending} a {Single} {Center}},\n\turl = {https://www.mdpi.com/2073-4425/12/11/1676},\n\tdoi = {10.3390/genes12111676},\n\tabstract = {Establishing the genotypes of patients with hyperphenylalaninemia (HPA)/phenylketonuria (PKU, MIM\\#261600) has been considered a cornerstone for rational medical management. However, knowledge of the phenylalanine hydroxylase gene (PAH) mutational spectrum in Latin American populations is still limited. Herein, we aim to update the mutational PAH spectrum in the largest cohort of HPA/PKU Mexican patients (N = 124) reported to date. The biallelic PAH genotype was investigated by Sanger automated sequencing, and genotypes were correlated with documented biochemical phenotypes and theoretical tetrahydrobiopterin (BH4) responsiveness. Patients were biochemically classified as having classic PKU (50\\%, 62/124), mild PKU (20.2\\%, 25/124) and mild HPA (29.8\\%, 37/124). Furthermore, 78.2\\% of the included patients (97/124) were identified by newborn screening. A total of 60 different pathogenic variants were identified, including three novel ones (c. 23del, c. 625\\_626insC and c. 1315 + 5\\_1315 + 6insGTGTAACAG), the main categories being missense changes (58\\%, 35/60) and those affecting the catalytic domain (56.6\\%, 34/60), and c. 60 + 5G \\&gt; T was the most frequent variant (14.5\\%, 36/248) mainly restricted (69.2\\%) to patients from the central and western parts of Mexico. These 60 types of variants constituted 100 different biallelic PAH genotypes, with the predominance of compound-heterozygous ones (96/124, 77\\%). The expected BH4 responsiveness based on the PAH genotype was estimated in 52\\% of patients (65/124), mainly due to the p. (Val388Met) (rs62516101) allele. Instead, our study identified 27 null variants with an allelic phenotype value of zero, with a predominance of c. 60 + 5G \\&gt; T, which predicts the absence of BH4 responsiveness. An identical genotype reported in BIOPKUdb was found in 92/124 (74\\%) of our patients, leading to a genotype–phenotype concordance in 80/92 (86.9\\%) of them. The high number of variants found confirms the heterogeneous and complex mutational landscape of HPA/PKU in Mexico.},\n\tlanguage = {en},\n\tnumber = {11},\n\turldate = {2021-11-01},\n\tjournal = {Genes},\n\tauthor = {Vela-Amieva, Marcela and Alcántara-Ortigoza, Miguel Angel and Ibarra-González, Isabel and González-del Angel, Ariadna and Fernández-Hernández, Liliana and Guillén-López, Sara and López-Mejía, Lizbeth and Carrillo-Nieto, Rosa Itzel and Belmont-Martínez, Leticia and Fernández-Lainez, Cynthia},\n\tmonth = oct,\n\tyear = {2021},\n\tnote = {Number: 11\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Alamut, Latin America, PAH molecular spectrum, newborn screening, phenylalanine, phenylketonuria, rare diseases, tetrahydrobiopterin},\n\tpages = {1676},\n}\n\n

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\n Establishing the genotypes of patients with hyperphenylalaninemia (HPA)/phenylketonuria (PKU, MIM#261600) has been considered a cornerstone for rational medical management. However, knowledge of the phenylalanine hydroxylase gene (PAH) mutational spectrum in Latin American populations is still limited. Herein, we aim to update the mutational PAH spectrum in the largest cohort of HPA/PKU Mexican patients (N = 124) reported to date. The biallelic PAH genotype was investigated by Sanger automated sequencing, and genotypes were correlated with documented biochemical phenotypes and theoretical tetrahydrobiopterin (BH4) responsiveness. Patients were biochemically classified as having classic PKU (50%, 62/124), mild PKU (20.2%, 25/124) and mild HPA (29.8%, 37/124). Furthermore, 78.2% of the included patients (97/124) were identified by newborn screening. A total of 60 different pathogenic variants were identified, including three novel ones (c. 23del, c. 625_626insC and c. 1315 + 5_1315 + 6insGTGTAACAG), the main categories being missense changes (58%, 35/60) and those affecting the catalytic domain (56.6%, 34/60), and c. 60 + 5G > T was the most frequent variant (14.5%, 36/248) mainly restricted (69.2%) to patients from the central and western parts of Mexico. These 60 types of variants constituted 100 different biallelic PAH genotypes, with the predominance of compound-heterozygous ones (96/124, 77%). The expected BH4 responsiveness based on the PAH genotype was estimated in 52% of patients (65/124), mainly due to the p. (Val388Met) (rs62516101) allele. Instead, our study identified 27 null variants with an allelic phenotype value of zero, with a predominance of c. 60 + 5G > T, which predicts the absence of BH4 responsiveness. An identical genotype reported in BIOPKUdb was found in 92/124 (74%) of our patients, leading to a genotype–phenotype concordance in 80/92 (86.9%) of them. The high number of variants found confirms the heterogeneous and complex mutational landscape of HPA/PKU in Mexico.\n

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\n \n\n \n \n \n \n \n \n Genetic predisposition in pediatric acute myocarditis: a pilot study.\n \n \n \n \n\n\n \n Gourzi, P; Pantou, M P; Vagenakis, G; Tsoutsinos, A; Vatsellas, G; Makrythanasis, P; Rammos, S; and Degiannis, D\n\n\n \n\n\n\n European Heart Journal, 42(Supplement_1). October 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Genetic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{gourzi_genetic_2021,\n\ttitle = {Genetic predisposition in pediatric acute myocarditis: a pilot study},\n\tvolume = {42},\n\tissn = {0195-668X},\n\tshorttitle = {Genetic predisposition in pediatric acute myocarditis},\n\turl = {https://doi.org/10.1093/eurheartj/ehab724.3197},\n\tdoi = {10.1093/eurheartj/ehab724.3197},\n\tabstract = {Myocarditis is an inflammatory disease of the heart muscle with a wide range of clinical presentations, from asymptomatic to cardiogenic shock and death. Although acute myocarditis is rare in pediatric population, it is caused by common viral infections, like parvovirus B19 or enteroviruses. Limited scientific evidence supports the existence of a genetic background that could underlay the susceptibility to virus-induced myocarditis.The aim of the present study was to identify mutations in genes associated with cardiomyopathies, that could possibly underly acute myocarditis in pediatric patients with biopsy-proven parvovirus B19 infection, verified by real time PCR.Nine pediatric patients presented in our center with acute myocarditis were genotyped with next generation sequencing using Clinical Exome Solution kit (Sophia Genetics) covering 4493 disease-related genes. Variant pathogenicity was accessed according to guidelines by American College of Medical Genetics (2015).Genetic analysis revealed that three of the nine patients were found positive for pathogenic/likely pathogenic mutations in TTR, ABCC6 and SLC22A5 genes. The patient that carried the SLC22A5 variant initially received telbivudine and her ejection fraction was improved from 20\\% to 45\\%. Genetic test results suggested that the patient may suffer from mild L-carnitine deficiency. Oral supplementation with high dose of L-carnitine during one month period improved dramatically her EF to normal (65\\%). The patient that carried the ABCC6 mutation, also carried a variant of unknown significance in MYH7 gene. Four patients carried variants of unknown significance. The variants of unknown significance detected in MYBPC3, SCN5A, and MYH7 genes are of particular interest since they accumulate evidence of pathogenicity. Two patients did not harbor any mutations.A significant proportion of rare variants in genes associated with cardiomyopathies has been identified in a small cohort of pediatric patients with parvovirus-induced acute myocarditis. The findings of our study, although limited, support the existence of a genetic background that could function as a predisposing factor influencing the clinical course of the disease.Type of funding sources: Foundation. Main funding source(s): Onassis Foundation},\n\tnumber = {Supplement\\_1},\n\turldate = {2021-11-01},\n\tjournal = {European Heart Journal},\n\tauthor = {Gourzi, P and Pantou, M P and Vagenakis, G and Tsoutsinos, A and Vatsellas, G and Makrythanasis, P and Rammos, S and Degiannis, D},\n\tmonth = oct,\n\tyear = {2021},\n}\n\n

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\n Myocarditis is an inflammatory disease of the heart muscle with a wide range of clinical presentations, from asymptomatic to cardiogenic shock and death. Although acute myocarditis is rare in pediatric population, it is caused by common viral infections, like parvovirus B19 or enteroviruses. Limited scientific evidence supports the existence of a genetic background that could underlay the susceptibility to virus-induced myocarditis.The aim of the present study was to identify mutations in genes associated with cardiomyopathies, that could possibly underly acute myocarditis in pediatric patients with biopsy-proven parvovirus B19 infection, verified by real time PCR.Nine pediatric patients presented in our center with acute myocarditis were genotyped with next generation sequencing using Clinical Exome Solution kit (Sophia Genetics) covering 4493 disease-related genes. Variant pathogenicity was accessed according to guidelines by American College of Medical Genetics (2015).Genetic analysis revealed that three of the nine patients were found positive for pathogenic/likely pathogenic mutations in TTR, ABCC6 and SLC22A5 genes. The patient that carried the SLC22A5 variant initially received telbivudine and her ejection fraction was improved from 20% to 45%. Genetic test results suggested that the patient may suffer from mild L-carnitine deficiency. Oral supplementation with high dose of L-carnitine during one month period improved dramatically her EF to normal (65%). The patient that carried the ABCC6 mutation, also carried a variant of unknown significance in MYH7 gene. Four patients carried variants of unknown significance. The variants of unknown significance detected in MYBPC3, SCN5A, and MYH7 genes are of particular interest since they accumulate evidence of pathogenicity. Two patients did not harbor any mutations.A significant proportion of rare variants in genes associated with cardiomyopathies has been identified in a small cohort of pediatric patients with parvovirus-induced acute myocarditis. The findings of our study, although limited, support the existence of a genetic background that could function as a predisposing factor influencing the clinical course of the disease.Type of funding sources: Foundation. Main funding source(s): Onassis Foundation\n

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\n \n\n \n \n \n \n \n \n Newly defined peroxisomal disease with novel ACBD5 mutation.\n \n \n \n \n\n\n \n Gorukmez, O.; Havalı, C.; Gorukmez, O.; and Dorum, S.\n\n\n \n\n\n\n Journal of Pediatric Endocrinology and Metabolism. October 2021.\n Publisher: De Gruyter\n\n\n\n
\n\n\n\n \n \n $\"Newly$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{gorukmez_newly_2021,\n\ttitle = {Newly defined peroxisomal disease with novel {ACBD5} mutation},\n\tissn = {2191-0251},\n\turl = {https://www.degruyter.com/document/doi/10.1515/jpem-2020-0352/html},\n\tdoi = {10.1515/jpem-2020-0352},\n\tabstract = {Peroxisomal disorders are a heterogeneous group of diseases caused by mutations in a large number of genes. One of the genetic disorders known to cause this situation is ACBD5 (Acyl-CoA binding-domain-containing-5) gene mutations that have been described in recent years. Here, we report two siblings with a novel homozygous nonsense variation (c.1297C\\&gt;T, p.Arg433*) in ACBD5 (NM\\_145698.4) gene using Clinical Exome Sequencing (Sophia Genetics).},\n\tlanguage = {en},\n\turldate = {2021-11-01},\n\tjournal = {Journal of Pediatric Endocrinology and Metabolism},\n\tauthor = {Gorukmez, Ozlem and Havalı, Cengiz and Gorukmez, Orhan and Dorum, Sevil},\n\tmonth = oct,\n\tyear = {2021},\n\tnote = {Publisher: De Gruyter},\n\tkeywords = {ACBD5, CES, clinical exome sequencing, novel mutation, peroxisomal disease},\n}\n\n

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\n \n\n \n \n \n \n \n \n Comprehensive Molecular Analysis of DMD Gene Increases the Diagnostic Value of Dystrophinopathies: A Pilot Study in a Southern Italy Cohort of Patients.\n \n \n \n \n\n\n \n De Palma, F. D. E.; Nunziato, M.; D’Argenio, V.; Savarese, M.; Esposito, G.; and Salvatore, F.\n\n\n \n\n\n\n Diagnostics, 11(10): 1910. October 2021.\n Number: 10 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Comprehensive$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{de_palma_comprehensive_2021,\n\ttitle = {Comprehensive {Molecular} {Analysis} of {DMD} {Gene} {Increases} the {Diagnostic} {Value} of {Dystrophinopathies}: {A} {Pilot} {Study} in a {Southern} {Italy} {Cohort} of {Patients}},\n\tvolume = {11},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tshorttitle = {Comprehensive {Molecular} {Analysis} of {DMD} {Gene} {Increases} the {Diagnostic} {Value} of {Dystrophinopathies}},\n\turl = {https://www.mdpi.com/2075-4418/11/10/1910},\n\tdoi = {10.3390/diagnostics11101910},\n\tabstract = {Duchenne/Becker muscular dystrophy (DMD/BMD) is an X-linked neuromuscular disease due to pathogenic sequence variations in the dystrophin (DMD) gene, one of the largest human genes. More than 70\\% of DMD gene defects result from genomic rearrangements principally leading to large deletions, while the remaining are small nucleotide variants, including nonsense and missense variants, small insertions/deletions or splicing alterations. Considering the large size of the gene and the wide mutational spectrum, the comprehensive molecular diagnosis of DMD/BMD is complex and may require several laboratory methods, thus increasing the time and costs of the analysis. In an attempt to simplify DMD/BMD molecular diagnosis workflow, we tested an NGS method suitable for the detection of all the different types of genomic variations that may affect the DMD gene. Forty previously analyzed patients were enrolled in this study and re-analyzed using the next generation sequencing (NGS)-based single-step procedure. The NGS results were compared with those from multiplex ligation-dependent probe amplification (MLPA)/multiplex PCR and/or Sanger sequencing. Most of the previously identified deleted/duplicated exons and point mutations were confirmed by NGS and 1 more pathogenic point mutation (a nonsense variant) was identified. Our results show that this NGS-based strategy overcomes limitations of traditionally used methods and is easily transferable to routine diagnostic procedures, thereby increasing the diagnostic power of DMD molecular analysis.},\n\tlanguage = {en},\n\tnumber = {10},\n\turldate = {2021-11-01},\n\tjournal = {Diagnostics},\n\tauthor = {De Palma, Fatima Domenica Elisa and Nunziato, Marcella and D’Argenio, Valeria and Savarese, Maria and Esposito, Gabriella and Salvatore, Francesco},\n\tmonth = oct,\n\tyear = {2021},\n\tnote = {Number: 10\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {DMD/BMD, Duchenne/Becker muscular dystrophy, MLPA, SOPHiA DDM, Sanger sequencing, dystrophin, molecular diagnostics, multiplex PCR, next-generation sequencing},\n\tpages = {1910},\n}\n\n

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\n \n\n \n \n \n \n \n \n Whole-genome amplification/preimplantation genetic testing for propionic acidemia of successful pregnancy in an obligate carrier Mexican couple: A case report.\n \n \n \n \n\n\n \n Adina Neumann, M. A. A.\n\n\n \n\n\n\n World Journal of Clinical Cases, 9(29): 8797–8803. October 2021.\n Publisher: Baishideng Publishing Group Inc.\n\n\n\n
\n\n\n\n \n \n $\"Whole-genome$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{adina_neumann_whole-genome_2021,\n\ttitle = {Whole-genome amplification/preimplantation genetic testing for propionic acidemia of successful pregnancy in an obligate carrier {Mexican} couple: {A} case report},\n\tvolume = {9},\n\tshorttitle = {Whole-genome amplification/preimplantation genetic testing for propionic acidemia of successful pregnancy in an obligate carrier {Mexican} couple},\n\turl = {https://www.wjgnet.com/2307-8960/full/v9/i29/8797.htm},\n\tdoi = {10.12998/wjcc.v9.i29.8797},\n\tabstract = {Whole-genome amplification/preimplantation genetic testing for propionic acidemia of successful pregnancy in an obligate carrier Mexican couple: A case report},\n\tlanguage = {en},\n\tnumber = {29},\n\turldate = {2021-10-19},\n\tjournal = {World Journal of Clinical Cases},\n\tauthor = {Adina Neumann, Miguel Angel Alcantara-Ortigoza},\n\tmonth = oct,\n\tyear = {2021},\n\tnote = {Publisher: Baishideng Publishing Group Inc.},\n\tkeywords = {Alamut},\n\tpages = {8797--8803},\n}\n\n

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\n \n\n \n \n \n \n \n \n SPIKE PROTEIN EVOLUTION IN THE SARS-CoV-2 DELTA VARIANT OF CONCERN: A CASE SERIES FROM NORTHERN LOMBARDY.\n \n \n \n \n\n\n \n Baj, A.; Novazzi, F.; Ferrante, F. D.; Genoni, A.; Tettamanzi, E.; Catanoso, G.; Gasperina, D. D.; Dentali, F.; Focosi, D.; and Maggi, F.\n\n\n \n\n\n\n Emerging Microbes & Infections, 0(ja): 1–10. October 2021.\n Publisher: Taylor & Francis _eprint: https://doi.org/10.1080/22221751.2021.1994356\n\n\n\n
\n\n\n\n \n \n $\"SPIKE$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{baj_spike_2021,\n\ttitle = {{SPIKE} {PROTEIN} {EVOLUTION} {IN} {THE} {SARS}-{CoV}-2 {DELTA} {VARIANT} {OF} {CONCERN}: {A} {CASE} {SERIES} {FROM} {NORTHERN} {LOMBARDY}},\n\tvolume = {0},\n\tissn = {null},\n\tshorttitle = {{SPIKE} {PROTEIN} {EVOLUTION} {IN} {THE} {SARS}-{CoV}-2 {DELTA} {VARIANT} {OF} {CONCERN}},\n\turl = {https://doi.org/10.1080/22221751.2021.1994356},\n\tdoi = {10.1080/22221751.2021.1994356},\n\tabstract = {The SARS-CoV-2 variant of concern (VOC) “Delta” is currently defined by PANGOLIN as a cluster of 33 different AY sublineages. Delta (in particular B.1.617.2) is largely and rapidly replacing the Alpha VOC as the dominant clade in most countries. To date, variations in the Spike protein of the Delta VOC have largely been limited. We report here the results of a genomic surveillance program from Northern Italy. We identified several Delta sublineages harboring mutations previously reported in GISAID at extremely low frequencies and in different combinations. Two patients (one of them vaccinated) tested positive for a Delta sublineage harboring S71F, T250I, T572I and K854N. More patients tested positive for G769 V plus C1248F, A352S, and R158G and C1248F, respectively. Genomic surveillance of Delta variants should be encouraged to anticipate immune escape and deploy countermeasures.},\n\tnumber = {ja},\n\turldate = {2021-10-19},\n\tjournal = {Emerging Microbes \\& Infections},\n\tauthor = {Baj, Andreina and Novazzi, Federica and Ferrante, Francesca Drago and Genoni, Angelo and Tettamanzi, Elena and Catanoso, Giuseppe and Gasperina, Daniela Dalla and Dentali, Francesco and Focosi, Daniele and Maggi, Fabrizio},\n\tmonth = oct,\n\tyear = {2021},\n\tpmid = {34651569},\n\tnote = {Publisher: Taylor \\& Francis\n\\_eprint: https://doi.org/10.1080/22221751.2021.1994356},\n\tkeywords = {A222 V, B.1.617.2, C1238F, COVID-19, Delta, G769 V, K854N, S71F, SARS-CoV-2, SOPHiA DDM, T250I, T572I, variant of concern},\n\tpages = {1--10},\n}\n\n

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\n \n\n \n \n \n \n \n \n Tumor BRCA testing in ovarian cancer and EQA scheme: our experience of a critical evaluation.\n \n \n \n \n\n\n \n De Paolis, E.; Concolino, P.; Onori, M. E.; Santonocito, C.; Marchetti, C.; Fagotti, A.; Scambia, G.; Urbani, A.; and Minucci, A.\n\n\n \n\n\n\n Molecular Biology Reports. October 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Tumor$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{de_paolis_tumor_2021,\n\ttitle = {Tumor {BRCA} testing in ovarian cancer and {EQA} scheme: our experience of a critical evaluation},\n\tissn = {1573-4978},\n\tshorttitle = {Tumor {BRCA} testing in ovarian cancer and {EQA} scheme},\n\turl = {https://doi.org/10.1007/s11033-021-06812-0},\n\tdoi = {10.1007/s11033-021-06812-0},\n\tabstract = {Next generation sequencing (NGS) is a widespread molecular biology method integrated into clinical practice to detect genetic variants, for diagnostic and prognostic purposes. The scheduled external quality assessments (EQA) is integral part of clinical molecular laboratory quality assurance. The EQA provides an efficient system to compare analytic test performances among different laboratories, which is essential to evaluate consistency of molecular test. EQA failures demands targeted corrective action plans. In this context, the complexity of the NGS techniques requires careful and continuous quality control procedures. We report a tumor BRCA1/2 (tBRCA) testing benchmark discrepancy provided by the European Molecular Genetics Quality Network in our laboratory during a round of EQA for somatic mutation testing of BRCA genes in relation to ovarian cancer. The critical analysis emerging from the tBRCA EQA is presented. We underline that harmonization processes are still required for the EQA in the molecular biology field, especially if applied to the evaluation of methods characterized by high complexity.},\n\tlanguage = {en},\n\turldate = {2021-10-19},\n\tjournal = {Molecular Biology Reports},\n\tauthor = {De Paolis, Elisa and Concolino, Paola and Onori, Maria Elisabetta and Santonocito, Concetta and Marchetti, Claudia and Fagotti, Anna and Scambia, Giovanni and Urbani, Andrea and Minucci, Angelo},\n\tmonth = oct,\n\tyear = {2021},\n\tkeywords = {CE-IVD, HCS},\n}\n\n

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\n \n\n \n \n \n \n \n \n Concurrent pathogenic variations in patients with hereditary cancer syndromes.\n \n \n \n \n\n\n \n Agaoglu, N. B.; and Doganay, L.\n\n\n \n\n\n\n European Journal of Medical Genetics, 64(12): 104366. October 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Concurrent$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{agaoglu_concurrent_2021,\n\ttitle = {Concurrent pathogenic variations in patients with hereditary cancer syndromes},\n\tvolume = {64},\n\tissn = {1769-7212},\n\turl = {https://www.sciencedirect.com/science/article/pii/S1769721221002329},\n\tdoi = {10.1016/j.ejmg.2021.104366},\n\tabstract = {Cancer is a multifactorial disorder; however, 5–10\\% of all cancers show hereditary background. In recent years many targeted next generation sequencing panels comprising cancer predisposition genes have been developed and used for diagnostic purposes in patients with increased cancer risk. Screening multiple genes at a time allows multiple variants in different genes to be detected as well. This study aims to determine the cases with concurrent mutations in different hereditary cancer predisposition genes and how they are clinically affected. Here, we screened 1090 index cases by next generation sequencing based hereditary cancer panels and evaluated the reflection of multiple variations on the phenotype. We detected 11 (1\\%) cases with pathogenic variants in more than one gene. These concurrent variations occurred mostly in BRCA1/2 (7/11) accompanied with MUTYH, ATM, CHECK2, NBN, and RAD50. In addition, MUTYH\\&ATM, NBN\\&MSH6, MUTYH\\&CHEK2 double heterozygous cases were detected. Moreover, we identified a case with three heterozygous variations in CDH1, MUTYH, and CHEK2. These patients presented malignancies that were mostly related to pathogenic variations they carried. Although they are rare, defining double heterozygous cases is important for managing appropriate therapy and accurate genetic consulting for the patients and family members.},\n\tlanguage = {en},\n\tnumber = {12},\n\turldate = {2021-10-19},\n\tjournal = {European Journal of Medical Genetics},\n\tauthor = {Agaoglu, Nihat Bugra and Doganay, Levent},\n\tmonth = oct,\n\tyear = {2021},\n\tkeywords = {Concurrent variations, Double heterozygous, Hereditary cancer, Next generation sequencing, SOPHiA DDM},\n\tpages = {104366},\n}\n\n

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\n \n\n \n \n \n \n \n \n Secondary Acute Myeloid Leukemia (sAML): Similarly Dismal Outcomes of AML after an antecedent hematologic disorder and therapy related AML.\n \n \n \n \n\n\n \n Lalayanni, C.; Gavriilaki, E.; Athanasiadou, A.; Iskas, M.; Papathanasiou, M.; Marvaki, A.; Mpesikli, S.; Papaioannou, G.; Mallouri, D.; Batsis, I.; Papalexandri, A.; Sakellari, I.; and Anagnostopoulos, A.\n\n\n \n\n\n\n Clinical Lymphoma Myeloma and Leukemia. October 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Secondary$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{lalayanni_secondary_2021,\n\ttitle = {Secondary {Acute} {Myeloid} {Leukemia} ({sAML}): {Similarly} {Dismal} {Outcomes} of {AML} after an antecedent hematologic disorder and therapy related {AML}},\n\tissn = {2152-2650},\n\tshorttitle = {Secondary {Acute} {Myeloid} {Leukemia} ({sAML})},\n\turl = {https://www.sciencedirect.com/science/article/pii/S2152265021020723},\n\tdoi = {10.1016/j.clml.2021.09.019},\n\tabstract = {Therapy related acute myeloid leukemia (tAML) and secondary AML after an antecedent hematologic disorder (sAML-AHD) are often addressed together, blurring any clinical and prognostic differences. Among 516 AML patients, we compared characteristics and outcomes of 149 patients with “sAML” (sAML-AHD: 104, tAML: 45), uniformly and intensively treated during the last 2 decades at one center. Clinical outcomes of the whole “sAML” cohort were significantly inferior compared to de novo AML and in both intermediate and poor cytogenetic risk groups. Adverse karyotype had no effect on survival in tAML, while it was a negative predictor in sAML-AHD. Both groups showed similarly dismal outcome, with low complete remission rates (CR 44\\% vs 41\\%) and median overall survival (OS 7 vs 10.5 months). Allogeneic hematopoietic cell transplantation (alloHCT) recipients in CR1 had superior median OS (24 vs 8 months). By multivariate analysis, alloHCT was an independent predictor of outcome, while karyotype was for sAML-AHD only. In conclusion, both “sAML” groups have inferior outcomes after chemotherapy, with adverse karyotype affecting primarily sAML-AHD. Until new treatment approaches are available, only alloHCT offers a survival advantage.\nMicro-abstract\n: Therapy related acute myeloid leukemia (tAML) and secondary AML after an antecedent hematologic disorder (sAML-AHD) are often addressed together, blurring any clinical and prognostic differences. Among 516 AML patients, we compared characteristics and outcomes of 149 patients with sAML. Both sAML groups have inferior outcomes after chemotherapy. By multivariate analysis, alloHCT was an independent predictor of outcome in both groups, while karyotype was for sAML-AHD only.},\n\tlanguage = {en},\n\turldate = {2021-10-05},\n\tjournal = {Clinical Lymphoma Myeloma and Leukemia},\n\tauthor = {Lalayanni, Chrysavgi and Gavriilaki, Eleni and Athanasiadou, Anastasia and Iskas, Michael and Papathanasiou, Maria and Marvaki, Anastasia and Mpesikli, Sotiria and Papaioannou, Giorgos and Mallouri, Despina and Batsis, Ioannis and Papalexandri, Apostolia and Sakellari, Ioanna and Anagnostopoulos, Achilles},\n\tmonth = oct,\n\tyear = {2021},\n\tkeywords = {MYS, allogeneic hematopoietic cell transplantation, secondary AML after an antecedent hematologic disorder, secondary acute myeloid leukemia, therapy related acute myeloid leukemia},\n}\n\n

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\n \n\n \n \n \n \n \n \n Two Decades after Mandibuloacral Dysplasia Discovery: Additional Cases and Comprehensive View of Disease Characteristics.\n \n \n \n \n\n\n \n Jéru, I.; Nabil, A.; El-Makkawy, G.; Lascols, O.; Vigouroux, C.; and Abdalla, E.\n\n\n \n\n\n\n Genes, 12(10): 1508. October 2021.\n Number: 10 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Two$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{jeru_two_2021,\n\ttitle = {Two {Decades} after {Mandibuloacral} {Dysplasia} {Discovery}: {Additional} {Cases} and {Comprehensive} {View} of {Disease} {Characteristics}},\n\tvolume = {12},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tshorttitle = {Two {Decades} after {Mandibuloacral} {Dysplasia} {Discovery}},\n\turl = {https://www.mdpi.com/2073-4425/12/10/1508},\n\tdoi = {10.3390/genes12101508},\n\tabstract = {Pathogenic variants in the LMNA gene cause a group of heterogeneous genetic disorders, called laminopathies. In particular, homozygous or compound heterozygous variants in LMNA have been associated with “mandibuloacral dysplasia type A” (MADA), an autosomal recessive disorder, characterized by mandibular hypoplasia, growth retardation mainly postnatal, pigmentary skin changes, progressive osteolysis of the distal phalanges and/or clavicles, and partial lipodystrophy. The detailed characteristics of this multisystemic disease have yet to be specified due to its rarity and the limited number of cases described. Here, we report three unrelated Egyptian patients with variable severity of MAD features. Next-generation sequencing using a gene panel revealed a homozygous c.1580G\\&gt;A-p.Arg527His missense variant in LMNA exon 9 in an affected individual with a typical MADA phenotype. Another homozygous c.1580G\\&gt;T-p.Arg527Leu variant affecting the same amino acid was identified in two additional patients, who both presented with severe manifestations very early in life. We combined our observations together with data from all MADA cases reported in the literature to get a clearer picture of the phenotypic variability in this disease. This work raises the number of reported MADA families, argues for the presence of the founder effect in Egypt, and strengthens genotype–phenotype correlations.},\n\tlanguage = {en},\n\tnumber = {10},\n\turldate = {2021-10-05},\n\tjournal = {Genes},\n\tauthor = {Jéru, Isabelle and Nabil, Amira and El-Makkawy, Gehad and Lascols, Olivier and Vigouroux, Corinne and Abdalla, Ebtesam},\n\tmonth = oct,\n\tyear = {2021},\n\tnote = {Number: 10\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Alamut, LMNA, SOPHiA DDM, acro-osteolysis, genotype–phenotype correlation, lipodystrophy, mandibuloacral dysplasia},\n\tpages = {1508},\n}\n\n

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\n \n\n \n \n \n \n \n \n Bilineal evolution of a U2AF1-mutated clone associated with acquisition of distinct secondary mutations.\n \n \n \n \n\n\n \n Montgomery, N. D; Galeotti, J.; Johnson, S. M.; Commander, L.; Weimer, E. T.; Chandra, P. K.; Nazir, T.; Alexander, T. B.; Zeidner, J. F.; and Foster, M. C\n\n\n \n\n\n\n Blood Advances, (bloodadvances.2021005308). October 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Bilineal$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{montgomery_bilineal_2021,\n\ttitle = {Bilineal evolution of a {U2AF1}-mutated clone associated with acquisition of distinct secondary mutations},\n\tissn = {2473-9529},\n\turl = {https://doi.org/10.1182/bloodadvances.2021005308},\n\tdoi = {10.1182/bloodadvances.2021005308},\n\tabstract = {Rare hematologic malignancies display evidence of both myeloid and lymphoid differentiation. Here, we describe such a novel bilineal event discovered in an adult woman with B-lymphoblastic leukemia (BLL). At the time of BLL diagnosis, the patient had a normal karyotype and a bulk sequencing panel identified pathogenic variants in BCOR, EZH2, RUNX1, and U2AF1, a genotype more typical of myeloid neoplasia. Additionally, the patient was noted to have 3-year history of cytopenias, and morphologic dyspoiesis was noted on post-treatment samples, raising the possibility of an antecedent hematologic disorder. To investigate the clonal architecture of her disease, we performed targeted sequencing on fractionated samples enriched for either B-lymphoblasts or circulating granulocytes. These studies revealed a truncal founder mutation in the spliceosome gene U2AF1 in both fractions, while distinct secondary mutations were present only in B-lymphoblasts (BCOR, NRAS) or myeloid cells (ASXL1, EZH2, RUNX1). These results indicate that both processes evolved from a common U2AF1-mutated precursor, which then acquired additional mutations during a process of divergent evolution and bilineal differentiation. Our findings highlight novel mechanisms in BLL leukemogenesis and expand the spectrum of observed bilineal neoplasms.},\n\tnumber = {bloodadvances.2021005308},\n\turldate = {2021-10-05},\n\tjournal = {Blood Advances},\n\tauthor = {Montgomery, Nathan D and Galeotti, Jonathan and Johnson, Steven M. and Commander, Leah and Weimer, Eric T. and Chandra, Pranil K. and Nazir, Tariq and Alexander, Thomas B. and Zeidner, Joshua F. and Foster, Matthew C},\n\tmonth = oct,\n\tyear = {2021},\n\tkeywords = {Custom, Custom Panel},\n}\n\n

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\n \n\n \n \n \n \n \n Approaches for diagnosis and treatment in neurotransmitter disorders of childhood.\n \n \n \n\n\n \n Havalı, C.; Dorum, S.; Ekici, A.; and Görükmez, Ö.\n\n\n \n\n\n\n Metabolic Brain Disease. September 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{havali_approaches_2021,\n\ttitle = {Approaches for diagnosis and treatment in neurotransmitter disorders of childhood},\n\tissn = {1573-7365},\n\tdoi = {10.1007/s11011-021-00838-w},\n\tabstract = {Neurotransmitter disorders are a group of neurometabolic syndromes caused by disturbances of neurotransmitter metabolism. The primary aim of this retrospective study is to present patients with disturbances of monoamine neurotransmitter metabolism. Cerebrospinal fluid (CSF) neurotransmitter measurements and genetic analysis were performed on five patients. Five patients who had various movement disorders and motor and cognitive disabilities were included. Four patients were diagnosed with sepiapterin reductase (SR) deficiency, and one was diagnosed with aromatic L-amino acid decarboxylase (AADC) deficiency. Different treatment responses appeared in patients with SR and AADC deficiency. The responses to drug treatment ranged from good to weak in our patients. The diagnosis process is challenging in patients with SR and AADC deficiency, which present similar clinical features to other neurological and metabolic diseases. Investigations of neurotransmitters in CSF and analysis of related genes are essential to differentiate disturbances of monoamine neurotransmitter metabolism from other neurometabolic diseases. For patients with monoamine neurotransmitter disorders, drugs that target these disturbances should be combined as necessary to produce the appropriate response.},\n\tlanguage = {eng},\n\tjournal = {Metabolic Brain Disease},\n\tauthor = {Havalı, Cengiz and Dorum, Sevil and Ekici, Arzu and Görükmez, Özlem},\n\tmonth = sep,\n\tyear = {2021},\n\tpmid = {34550503},\n\tkeywords = {AADC deficiency movement disorders, CES, Clinical Exome, Inherited neurotransmitter disorders, Monoamine metabolism, Sepiapterin reductase},\n}\n\n

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\n \n\n \n \n \n \n \n \n A Deletion in the N Gene May Cause Diagnostic Escape in SARS-COV-2 Samples.\n \n \n \n \n\n\n \n Zannoli, S.; Dirani, G.; Taddei, F.; Gatti, G.; Poggianti, I.; Denicolò, A.; Arfilli, V.; Manera, M.; Mancini, A.; Battisti, A.; and Sambri, V.\n\n\n \n\n\n\n Diagnostic Microbiology and Infectious Disease,115540. September 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{zannoli_deletion_2021,\n\ttitle = {A {Deletion} in the {N} {Gene} {May} {Cause} {Diagnostic} {Escape} in {SARS}-{COV}-2 {Samples}},\n\tissn = {0732-8893},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0732889321002327},\n\tdoi = {10.1016/j.diagmicrobio.2021.115540},\n\tabstract = {Five SARS-CoV-2-positive samples showed N-gene drop-out with a RT-PCR multiplex test. WGS found all samples to harbor a deletion in the same region of the N gene, which is likely to impair the efficiency of amplification. This highlights the need for a continued surveillance of viral evolution and diagnostic test performance.},\n\tlanguage = {en},\n\turldate = {2021-09-21},\n\tjournal = {Diagnostic Microbiology and Infectious Disease},\n\tauthor = {Zannoli, Silvia and Dirani, Giorgio and Taddei, Francesca and Gatti, Giulia and Poggianti, Ilaria and Denicolò, Agnese and Arfilli, Valentina and Manera, Martina and Mancini, Andrea and Battisti, Arianna and Sambri, Vittorio},\n\tmonth = sep,\n\tyear = {2021},\n\tkeywords = {B.1.1.7, RT-PCR, SARS-CoV-2 variants, SOPHiA DDM, diagnostic escape, whole genome sequencing},\n\tpages = {115540},\n}\n\n

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\n \n\n \n \n \n \n \n \n Left Ventricular Myocardial Noncompaction with Advanced Atrioventricular Conduction Disorder and Ventricular Arrhythmias in a Young Patient: Role of MIB1 Gene.\n \n \n \n \n\n\n \n Balla, C.; De Raffele, M.; Deserio, M. A.; Sanchini, M.; Farnè, M.; Trabanelli, C.; Ragni, L.; Biffi, M.; Ferlini, A.; Rapezzi, C.; Gualandi, F.; and Bertini, M.\n\n\n \n\n\n\n Journal of Cardiovascular Development and Disease, 8(9): 109. September 2021.\n Number: 9 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Left$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{balla_left_2021,\n\ttitle = {Left {Ventricular} {Myocardial} {Noncompaction} with {Advanced} {Atrioventricular} {Conduction} {Disorder} and {Ventricular} {Arrhythmias} in a {Young} {Patient}: {Role} of {MIB1} {Gene}},\n\tvolume = {8},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tshorttitle = {Left {Ventricular} {Myocardial} {Noncompaction} with {Advanced} {Atrioventricular} {Conduction} {Disorder} and {Ventricular} {Arrhythmias} in a {Young} {Patient}},\n\turl = {https://www.mdpi.com/2308-3425/8/9/109},\n\tdoi = {10.3390/jcdd8090109},\n\tabstract = {Left ventricular noncompaction (LVNC) is a structural abnormality of the left ventricle, usually described as an isolated condition, or sometimes associated with other structural cardiac diseases. LVNC is generally asymptomatic, although it may present conduction disorders, arrhythmias, and heart failure. Here, we present the case of a patient who came to our attention with a severe LVNC phenotype associated with advanced AV conduction disorder, and supraventricular and ventricular arrhythmias at young age, in which a novel MIB1, likely pathogenic, variation has been identified.},\n\tlanguage = {en},\n\tnumber = {9},\n\turldate = {2021-09-16},\n\tjournal = {Journal of Cardiovascular Development and Disease},\n\tauthor = {Balla, Cristina and De Raffele, Martina and Deserio, Maria Angela and Sanchini, Mariabeatrice and Farnè, Marianna and Trabanelli, Cecilia and Ragni, Luca and Biffi, Mauro and Ferlini, Alessandra and Rapezzi, Claudio and Gualandi, Francesca and Bertini, Matteo},\n\tmonth = sep,\n\tyear = {2021},\n\tnote = {Number: 9\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {MIB1, SOPHiA DDM, advanced atrioventricular block, left ventricular noncompaction},\n\tpages = {109},\n}\n\n

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\n \n\n \n \n \n \n \n \n Advances in Computational Biosciences Protocols.\n \n \n \n \n\n\n \n Sarkar, A. A.\n\n\n \n\n\n\n Genetic Engineering & Biotechnology News, 41(P1): P43–P45. September 2021.\n Publisher: Mary Ann Liebert, Inc., publishers\n\n\n\n
\n\n\n\n \n \n $\"Advances$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{sarkar_advances_2021,\n\ttitle = {Advances in {Computational} {Biosciences} {Protocols}},\n\tvolume = {41},\n\tissn = {1935-472X},\n\turl = {https://www.liebertpub.com/doi/full/10.1089/gen.41.P1.15},\n\tdoi = {10.1089/gen.41.P1.15},\n\tnumber = {P1},\n\turldate = {2021-09-16},\n\tjournal = {Genetic Engineering \\& Biotechnology News},\n\tauthor = {Sarkar, Anjali A.},\n\tmonth = sep,\n\tyear = {2021},\n\tnote = {Publisher: Mary Ann Liebert, Inc., publishers},\n\tkeywords = {Artificial intelligence, SOPHiA DDM},\n\tpages = {P43--P45},\n}\n\n

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\n \n\n \n \n \n \n \n \n Mutations in MYBPC3 and MYH7 in Association with Brugada Type 1 ECG Pattern: Overlap between Brugada Syndrome and Hypertrophic Cardiomyopathy?.\n \n \n \n \n\n\n \n Farnè, M.; Balla, C.; Margutti, A.; Selvatici, R.; De Raffele, M.; Di Domenico, A.; Imbrici, P.; De Maria, E.; Biffi, M.; Bertini, M.; Rapezzi, C.; Ferlini, A.; and Gualandi, F.\n\n\n \n\n\n\n Cardiogenetics, 11(3): 139–147. September 2021.\n Number: 3 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Mutations$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{farne_mutations_2021,\n\ttitle = {Mutations in {MYBPC3} and {MYH7} in {Association} with {Brugada} {Type} 1 {ECG} {Pattern}: {Overlap} between {Brugada} {Syndrome} and {Hypertrophic} {Cardiomyopathy}?},\n\tvolume = {11},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tshorttitle = {Mutations in {MYBPC3} and {MYH7} in {Association} with {Brugada} {Type} 1 {ECG} {Pattern}},\n\turl = {https://www.mdpi.com/2035-8148/11/3/16},\n\tdoi = {10.3390/cardiogenetics11030016},\n\tabstract = {Brugada syndrome (BrS) is an inherited disorder with high allelic and genetic heterogeneity clinically characterized by typical coved-type ST segment elevation at the electrocardiogram (ECG), which may occur either spontaneously or after provocative drug testing. BrS is classically described as an arrhythmic condition occurring in a structurally normal heart and is associated with the risk of ventricular fibrillation and sudden cardiac death (SCD). We studied five patients with spontaneous or drug-induced type 1 ECG pattern, variably associated with symptoms and a positive family history through a Next Generation Sequencing panels approach, which includes genes of both channelopathies and cardiomyopathies. We identified variants in MYBPC3 and in MYH7, hypertrophic cardiomyopathy (HCM) genes (MYBPC3: p.Lys1065Glnfs*12 and c.1458-1G \\&gt; A, MYH7: p.Arg783His, p.Val1213Met, p.Lys744Thr). Our data propose that Brugada type 1 ECG may be an early electrocardiographic marker of a concealed structural heart disease, possibly enlarging the genotypic overlap between Brugada syndrome and cardiomyopathies.},\n\tlanguage = {en},\n\tnumber = {3},\n\turldate = {2021-09-15},\n\tjournal = {Cardiogenetics},\n\tauthor = {Farnè, Marianna and Balla, Cristina and Margutti, Alice and Selvatici, Rita and De Raffele, Martina and Di Domenico, Assunta and Imbrici, Paola and De Maria, Elia and Biffi, Mauro and Bertini, Matteo and Rapezzi, Claudio and Ferlini, Alessandra and Gualandi, Francesca},\n\tmonth = sep,\n\tyear = {2021},\n\tnote = {Number: 3\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Brugada syndrome, MYBPC3, MYH7, SOPHiA DDM, hypertrophic cardiomyopathy, overlapping phenotypes, sarcomeric genes},\n\tpages = {139--147},\n}\n\n

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\n \n\n \n \n \n \n \n \n International initiative for a curated SDHB variant database improving the diagnosis of hereditary paraganglioma and pheochromocytoma.\n \n \n \n \n\n\n \n Aim, L. B.; Maher, E. R.; Cascon, A.; Barlier, A.; Giraud, S.; Ercolino, T.; Pigny, P.; Clifton-Bligh, R. J.; Mirebeau-Prunier, D.; Mohamed, A.; Favier, J.; Gimenez-Roqueplo, A.; Schiavi, F.; Toledo, R. A.; Dahia, P. L.; Robledo, M.; Bayley, J. P.; and Burnichon, N.\n\n\n \n\n\n\n Journal of Medical Genetics. August 2021.\n Publisher: BMJ Publishing Group Ltd Section: Cancer genetics\n\n\n\n
\n\n\n\n \n \n $\"International$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 7 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{aim_international_2021,\n\ttitle = {International initiative for a curated {SDHB} variant database improving the diagnosis of hereditary paraganglioma and pheochromocytoma},\n\tcopyright = {© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.},\n\tissn = {0022-2593, 1468-6244},\n\turl = {https://jmg.bmj.com/content/early/2021/08/26/jmedgenet-2020-107652},\n\tdoi = {10.1136/jmedgenet-2020-107652},\n\tabstract = {Background SDHB is one of the major genes predisposing to paraganglioma/pheochromocytoma (PPGL). Identifying pathogenic SDHB variants in patients with PPGL is essential to the management of patients and relatives due to the increased risk of recurrences, metastases and the emergence of non-PPGL tumours. In this context, the ‘NGS and PPGL (NGSnPPGL) Study Group’ initiated an international effort to collect, annotate and classify SDHB variants and to provide an accurate, expert-curated and freely available SDHB variant database.\nMethods A total of 223 distinct SDHB variants from 737 patients were collected worldwide. Using multiple criteria, each variant was first classified according to a 5-tier grouping based on American College of Medical Genetics and NGSnPPGL standardised recommendations and was then manually reviewed by a panel of experts in the field.\nResults This multistep process resulted in 23 benign/likely benign, 149 pathogenic/likely pathogenic variants and 51 variants of unknown significance (VUS). Expert curation reduced by half the number of variants initially classified as VUS. Variant classifications are publicly accessible via the Leiden Open Variation Database system (https://databases.lovd.nl/shared/genes/SDHB).\nConclusion This international initiative by a panel of experts allowed us to establish a consensus classification for 223 SDHB variants that should be used as a routine tool by geneticists in charge of PPGL laboratory diagnosis. This accurate classification of SDHB genetic variants will help to clarify the diagnosis of hereditary PPGL and to improve the clinical care of patients and relatives with PPGL.},\n\tlanguage = {en},\n\turldate = {2021-09-09},\n\tjournal = {Journal of Medical Genetics},\n\tauthor = {Aim, Laurene Ben and Maher, Eamonn R. and Cascon, Alberto and Barlier, Anne and Giraud, Sophie and Ercolino, Tonino and Pigny, Pascal and Clifton-Bligh, Roderick J. and Mirebeau-Prunier, Delphine and Mohamed, Amira and Favier, Judith and Gimenez-Roqueplo, Anne-Paule and Schiavi, Francesca and Toledo, Rodrigo A. and Dahia, Patricia L. and Robledo, Mercedes and Bayley, Jean Pierre and Burnichon, Nelly},\n\tmonth = aug,\n\tyear = {2021},\n\tpmid = {34452955},\n\tnote = {Publisher: BMJ Publishing Group Ltd\nSection: Cancer genetics},\n\tkeywords = {Alamut, adrenal gland diseases, databases, genetic, genetic testing, genetic variation, human genetics},\n}\n\n

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\n \n\n \n \n \n \n \n \n Performance Evaluation of SpliceAI for the Prediction of Splicing of NF1 Variants.\n \n \n \n \n\n\n \n Ha, C.; Kim, J.; and Jang, J.\n\n\n \n\n\n\n Genes, 12(9): 1308. August 2021.\n Number: 9 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Performance$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{ha_performance_2021,\n\ttitle = {Performance {Evaluation} of {SpliceAI} for the {Prediction} of {Splicing} of {NF1} {Variants}},\n\tvolume = {12},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\turl = {https://www.mdpi.com/2073-4425/12/9/1308},\n\tdoi = {10.3390/genes12091308},\n\tabstract = {Neurofibromatosis type 1, characterized by neurofibromas and café-au-lait macules, is one of the most common genetic disorders caused by pathogenic NF1 variants. Because of the high proportion of splicing mutations in NF1, identifying variants that alter splicing may be an essential issue for laboratories. Here, we investigated the sensitivity and specificity of SpliceAI, a recently introduced in silico splicing prediction algorithm in conjunction with other in silico tools. We evaluated 285 NF1 variants identified from 653 patients. The effect on variants on splicing alteration was confirmed by complementary DNA sequencing followed by genomic DNA sequencing. For in silico prediction of splicing effects, we used SpliceAI, MaxEntScan (MES), and Splice Site Finder-like (SSF). The sensitivity and specificity of SpliceAI were 94.5\\% and 94.3\\%, respectively, with a cut-off value of Δ Score \\&gt; 0.22. The area under the curve of SpliceAI was 0.975 (p \\&lt; 0.0001). Combined analysis of MES/SSF showed a sensitivity of 83.6\\% and specificity of 82.5\\%. The concordance rate between SpliceAI and MES/SSF was 84.2\\%. SpliceAI showed better performance for the prediction of splicing alteration for NF1 variants compared with MES/SSF. As a convenient web-based tool, SpliceAI may be helpful in clinical laboratories conducting DNA-based NF1 sequencing.},\n\tlanguage = {en},\n\tnumber = {9},\n\turldate = {2021-09-09},\n\tjournal = {Genes},\n\tauthor = {Ha, Changhee and Kim, Jong-Won and Jang, Ja-Hyun},\n\tmonth = aug,\n\tyear = {2021},\n\tnote = {Number: 9\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Alamut, NF1, SpliceAI, in silico predictions, neurofibromatosis type 1, splice variants},\n\tpages = {1308},\n}\n\n

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\n \n\n \n \n \n \n \n \n NGS and phenotypic ontology-based approaches increase the diagnostic yield in syndromic retinal diseases.\n \n \n \n \n\n\n \n Perea-Romero, I.; Blanco-Kelly, F.; Sanchez-Navarro, I.; Lorda-Sanchez, I.; Tahsin-Swafiri, S.; Avila-Fernandez, A.; Martin-Merida, I.; Trujillo-Tiebas, M. J.; Lopez-Rodriguez, R.; Rodriguez de Alba, M.; Iancu, I. F.; Romero, R.; Quinodoz, M.; Hakonarson, H.; Garcia-Sandova, B.; Minguez, P.; Corton, M.; Rivolta, C.; and Ayuso, C.\n\n\n \n\n\n\n Human Genetics. August 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"NGS$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{perea-romero_ngs_2021,\n\ttitle = {{NGS} and phenotypic ontology-based approaches increase the diagnostic yield in syndromic retinal diseases},\n\tissn = {1432-1203},\n\turl = {https://doi.org/10.1007/s00439-021-02343-7},\n\tdoi = {10.1007/s00439-021-02343-7},\n\tabstract = {Syndromic retinal diseases (SRDs) are a group of complex inherited systemic disorders, with challenging molecular underpinnings and clinical management. Our main goal is to improve clinical and molecular SRDs diagnosis, by applying a structured phenotypic ontology and next-generation sequencing (NGS)-based pipelines. A prospective and retrospective cohort study was performed on 100 probands with an a priori diagnosis of non-Usher SRDs, using available clinical data, including Human Phenotype Ontology annotation, and further classification into seven clinical categories (ciliopathies, specific syndromes and five others). Retrospective molecular diagnosis was assessed using different molecular and bioinformatic methods depending on availability. Subsequently, uncharacterized probands were prospectively screened using other NGS approaches to extend the number of analyzed genes. After phenotypic classification, ciliopathies were the most common SRD (35\\%). A global characterization rate of 52\\% was obtained, with six cases incompletely characterized for a gene that partially explained the phenotype. An improved characterization rate was achieved addressing prospective cases (83\\%) and well-recognizable syndrome (62\\%) subgroups. The 27\\% of the fully characterized cases were reclassified into a different clinical category after identification of the disease-causing gene. Clinical-exome sequencing is the most appropriate first-tier approach for prospective cases, whereas whole-exome sequencing and bioinformatic reanalysis increases the diagnosis of uncharacterized retrospective cases to 45\\%, mostly those with unspecific symptoms. Our study describes a comprehensive approach to SRDs in daily clinical practice and the importance of thorough clinical assessment and selection of the most appropriate molecular test to be used to solve these complex cases and elucidate novel associations.},\n\tlanguage = {en},\n\turldate = {2021-09-09},\n\tjournal = {Human Genetics},\n\tauthor = {Perea-Romero, I. and Blanco-Kelly, F. and Sanchez-Navarro, I. and Lorda-Sanchez, I. and Tahsin-Swafiri, S. and Avila-Fernandez, A. and Martin-Merida, I. and Trujillo-Tiebas, M. J. and Lopez-Rodriguez, R. and Rodriguez de Alba, M. and Iancu, I. F. and Romero, R. and Quinodoz, M. and Hakonarson, H. and Garcia-Sandova, Blanca and Minguez, P. and Corton, M. and Rivolta, C. and Ayuso, C.},\n\tmonth = aug,\n\tyear = {2021},\n\tkeywords = {CES, SOPHiA DDM},\n}\n\n

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\n \n\n \n \n \n \n \n \n Isolated juvenile macular dystrophy without posterior column ataxia associated with FLVCR1 mutation.\n \n \n \n \n\n\n \n Lachmann, E. S.; Mautone, L.; and Dulz, S.\n\n\n \n\n\n\n Ophthalmic Genetics, 0(0): 1–3. August 2021.\n Publisher: Taylor & Francis _eprint: https://doi.org/10.1080/13816810.2021.1970196\n\n\n\n
\n\n\n\n \n \n $\"Isolated$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{lachmann_isolated_2021,\n\ttitle = {Isolated juvenile macular dystrophy without posterior column ataxia associated with {FLVCR1} mutation},\n\tvolume = {0},\n\tissn = {1381-6810},\n\turl = {https://doi.org/10.1080/13816810.2021.1970196},\n\tdoi = {10.1080/13816810.2021.1970196},\n\tnumber = {0},\n\turldate = {2021-09-09},\n\tjournal = {Ophthalmic Genetics},\n\tauthor = {Lachmann, Eva S. and Mautone, Luca and Dulz, Simon},\n\tmonth = aug,\n\tyear = {2021},\n\tpmid = {34433355},\n\tnote = {Publisher: Taylor \\& Francis\n\\_eprint: https://doi.org/10.1080/13816810.2021.1970196},\n\tkeywords = {CES, Retinal Dystrophies},\n\tpages = {1--3},\n}\n\n

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\n \n\n \n \n \n \n \n \n Methodology, clinical applications, and future directions of body composition analysis of computed tomography (CT) images: A review.\n \n \n \n \n\n\n \n Tolonen, A.; Pakarinen, T.; Sassi, A.; Kyttä, J.; Cancino, W.; Rinta-Kiikka, I.; Pertuz, S.; and Arponen, O.\n\n\n \n\n\n\n European Journal of Radiology,109943. August 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Methodology,$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{tolonen_methodology_2021,\n\ttitle = {Methodology, clinical applications, and future directions of body composition analysis of computed tomography ({CT}) images: {A} review},\n\tissn = {0720-048X},\n\tshorttitle = {Methodology, clinical applications, and future directions of body composition analysis of computed tomography ({CT}) images},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0720048X21004241},\n\tdoi = {10.1016/j.ejrad.2021.109943},\n\tabstract = {Purpose\nof the review We aim to review the methods, current research evidence, and future directions of body composition analysis (BCA) with CT imaging.\nRecent findings\nCT images can be used to evaluate muscle, visceral, and subcutaneous adipose tissue (VAT and SAT, respectively) compartments. Manual and semiautomatic segmentations of the tissue compartments are still the gold standards. The segmentation of skeletal muscle tissue, VAT and SAT compartments is most often performed at the level of the 3rd lumbar vertebra. A decreased amount of the CT-determined skeletal muscle mass is a marker of impaired survival in many patient populations, including patients with cancer and those undergoing several types of surgery or admitted to the intensive care unit (ICU). Patients with increased VAT are more susceptible to impaired survival / worse outcomes; those patients who are critically ill / admitted ICU or who will undergo surgery appear to be an exception. The independent significance of SAT is less well established. Recently, the roles of the CT-determined decrease of muscle mass and increased VAT and epicardial adipose tissue (EAT) areas have been shown to predict a more debilitating course of illness in patients suffering from severe acute respiratory syndrome after coronavirus 2 (COVID-19) infection.\nSummary\nThe field of CT-based body composition analysis is rapidly evolving and shows great potential for clinical implementation.},\n\tlanguage = {en},\n\turldate = {2021-09-07},\n\tjournal = {European Journal of Radiology},\n\tauthor = {Tolonen, Antti and Pakarinen, Tomppa and Sassi, Antti and Kyttä, Jere and Cancino, William and Rinta-Kiikka, Irina and Pertuz, Said and Arponen, Otso},\n\tmonth = aug,\n\tyear = {2021},\n\tkeywords = {Body Composition, Body Composition Analysis, Computed Tomography, Radiomics, Sarcopenia},\n\tpages = {109943},\n}\n\n

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\n \n\n \n \n \n \n \n \n Pathogenicity Reclassification of Genetic Variants Related to Early-Onset Breast Cancer among Buryat Women.\n \n \n \n \n\n\n \n Gervas, P.; Molokov, A.; Kiselev, A.; Zarubin, A.; Yumov, E.; Pisareva, L.; Choynzonov, E. C. E.; and Cherdyntseva, N.\n\n\n \n\n\n\n Technical Report September 2021.\n ISSN: 2693-5015 Type: article\n\n\n\n
\n\n\n\n \n \n $\"Pathogenicity$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@techreport{gervas_pathogenicity_2021,\n\ttitle = {Pathogenicity {Reclassification} of {Genetic} {Variants} {Related} to {Early}-{Onset} {Breast} {Cancer} among {Buryat} {Women}},\n\turl = {https://www.researchsquare.com/article/rs-783155/v1},\n\tabstract = {Background: Germline alterations in ATM, BRCA1, BRCA2, and other genes are responsible for early-onset breast cancer. However, up to 20\\% of\\&amp;nbsp;molecular tests report genetic variant of unknown significance (VUS) or novel variants that have never been previously described and their clinical significance are unknown. An existing open access databases (ClinVar, BIC, and ENIGMA and other) play an important role in the interpretation of VUS, but in Asian populations the interpretation of VUS is still difficult due to restricted data. This study aimed to reclassify the genetic variants by using the ActiveDriveDB database that annotates variants through the lens of sites of post-translational modifications.Methods: Our study included young Buryat BC patients, anthropologically belonging to the Central Asia. Genomic DNA was used to prepare libraries. NGS sequencing was performed on a NextSeq 500 System. Results: We re-examined 135 rare variants (41 VUS, 25 conflicting, 64 benign and 5 new variants). We identified 10 out of 135 (7.4\\%) mutations that affected the sites of post-translational modification in proteins. Of 135 rare mutations, 1 benign variant was reclassified as network-rewiring - motif loss mutation, 3 VUS and 1 new variant were reclassified as distal PTM- mutations, 2 new and 1 benign variant were classified as proximal PTM- mutations and 1 benign and 1 conflicting variant were classified as direct PTM- mutations.Conclusions: For the first time, 7.4\\% (10 out of 135) of mutations that affected the sites of post-translational modification in proteins were identified among Buryat women with early-onset breast cancer.},\n\turldate = {2021-09-07},\n\tauthor = {Gervas, Polina and Molokov, Aleksey and Kiselev, Artem and Zarubin, Aleksei and Yumov, Evgeny and Pisareva, Lubov and Choynzonov, Evgeny Choynzonov Evgeny and Cherdyntseva, Nadezda},\n\tmonth = sep,\n\tyear = {2021},\n\tdoi = {10.21203/rs.3.rs-783155/v1},\n\tnote = {ISSN: 2693-5015\nType: article},\n}\n\n

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\n \n\n \n \n \n \n \n \n Engraftment characterization of risk-stratified AML patients in NSGS mice.\n \n \n \n \n\n\n \n Diaz de la Guardia, R.; Velasco-Hernandez, T.; Gutierrez-Agüera, F.; Roca-Ho, H.; Molina, O.; Nombela-Arrieta, C.; Bataller, A.; Fuster, J. L.; Anguita, E.; Vives, S.; Zamora, L.; Nomdedeu, J. F; Gomez-Casares, M. T.; Ramírez-Orellana, M.; Lapillonne, H.; Ramos-Mejia, V.; Rodríguez-Manzaneque, J. C.; Bueno, C.; Lopez-Millan, B.; and Menendez, P.\n\n\n \n\n\n\n Blood Advances, (bloodadvances.2020003958). September 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Engraftment$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{diaz_de_la_guardia_engraftment_2021,\n\ttitle = {Engraftment characterization of risk-stratified {AML} patients in {NSGS} mice},\n\tissn = {2473-9529},\n\turl = {https://doi.org/10.1182/bloodadvances.2020003958},\n\tdoi = {10.1182/bloodadvances.2020003958},\n\tabstract = {Acute myeloid leukemia (AML) is the commonest acute leukemia in adults. Disease heterogeneity is well-documented and patient stratification determines treatment decisions. Patient-derived xenografts (PDXs) of risk-stratified AMLs are crucial for studying AML biology and testing novel therapeutics. Despite recent advances in PDX modeling of AML, reproducible engraftment of human AML is mainly limited to high-risk (HR) cases, with inconsistent or very protracted engraftment observed for favorable-risk (FR) and intermediate-risk (IR) patients. We have characterized the engraftment robustness/kinetics in NSGS mice of 28 AML patients grouped according to molecular/cytogenetic classification, and have assessed whether the orthotopic co-administration of patient-matched bone marrow mesenchymal stromal cells (BM-MSCs) improves AML engraftment. PDX event-free survival correlated well with the predictable prognosis of risk-stratified AML patients. The majority (85\\%-94\\%) of the mice were engrafted in BM independently of the risk group, although HR-AML patients showed engraftment levels significantly superior to those of FR- and IR-AML patients. Importantly, the engraftment levels observed in NSGS mice by week 6 remained stable overtime. Serial transplantation and long-term culture-initiating cell (LTC-IC) assays revealed long-term engraftment limited to HR-AML patients, fitter leukemia-initiating cells (LICs) in HR- than in FR- or IR-AML samples, and the presence of AML-LICs in the CD34- leukemic fraction, regardless the risk group. Finally, orthotopic co-administration of patient-matched BM-MSCs with AML cells resulted dispensable for BM engraftment levels but favored peripheralization of engrafted AML cells. This comprehensive characterization of human AML engraftment in NSGS mice offers a valuable platform for in vivo testing of targeted therapies in risk-stratified AML patient samples.},\n\tnumber = {bloodadvances.2020003958},\n\turldate = {2021-09-07},\n\tjournal = {Blood Advances},\n\tauthor = {Diaz de la Guardia, Rafael and Velasco-Hernandez, Talia and Gutierrez-Agüera, Francisco and Roca-Ho, Heleia and Molina, Oscar and Nombela-Arrieta, Cesar and Bataller, Alex and Fuster, Jose Luis and Anguita, Eduardo and Vives, Susana and Zamora, Lurdes and Nomdedeu, Josep F and Gomez-Casares, M. Teresa and Ramírez-Orellana, Manuel and Lapillonne, Helene and Ramos-Mejia, Veronica and Rodríguez-Manzaneque, Juan Carlos and Bueno, Clara and Lopez-Millan, Belen and Menendez, Pablo},\n\tmonth = sep,\n\tyear = {2021},\n}\n\n

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\n \n\n \n \n \n \n \n \n Attention Deficit Hyperactivity and Autism Spectrum Disorders as the Core Symptoms of AUTS2 Syndrome: Description of Five New Patients and Update of the Frequency of Manifestations and Genotype-Phenotype Correlation.\n \n \n \n \n\n\n \n Sanchez-Jimeno, C.; Blanco-Kelly, F.; López-Grondona, F.; Losada-Del Pozo, R.; Moreno, B.; Rodrigo-Moreno, M.; Martinez-Cayuelas, E.; Riveiro-Alvarez, R.; Fenollar-Cortés, M.; Ayuso, C.; Rodríguez de Alba, M.; Lorda-Sanchez, I.; and Almoguera, B.\n\n\n \n\n\n\n Genes, 12(9): 1360. August 2021.\n Number: 9 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Attention$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{sanchez-jimeno_attention_2021,\n\ttitle = {Attention {Deficit} {Hyperactivity} and {Autism} {Spectrum} {Disorders} as the {Core} {Symptoms} of {AUTS2} {Syndrome}: {Description} of {Five} {New} {Patients} and {Update} of the {Frequency} of {Manifestations} and {Genotype}-{Phenotype} {Correlation}},\n\tvolume = {12},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tshorttitle = {Attention {Deficit} {Hyperactivity} and {Autism} {Spectrum} {Disorders} as the {Core} {Symptoms} of {AUTS2} {Syndrome}},\n\turl = {https://www.mdpi.com/2073-4425/12/9/1360},\n\tdoi = {10.3390/genes12091360},\n\tabstract = {Haploinsufficiency of AUTS2 has been associated with a syndromic form of neurodevelopmental delay characterized by intellectual disability, autistic features, and microcephaly, also known as AUTS2 syndrome. While the phenotype associated with large deletions and duplications of AUTS2 is well established, clinical features of patients harboring AUTS2 sequence variants have not been extensively described. In this study, we describe the phenotype of five new patients with AUTS2 pathogenic variants, three of them harboring loss-of-function sequence variants. The phenotype of the patients was characterized by attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) or autistic features and mild global developmental delay (GDD) or intellectual disability (ID), all in 4/5 patients (80\\%), a frequency higher than previously reported for ADHD and autistic features. Microcephaly and short stature were found in 60\\% of the patients; and feeding difficulties, generalized hypotonia, and ptosis, were each found in 40\\%. We also provide the aggregated frequency of the 32 items included in the AUTS2 syndrome severity score (ASSS) in patients currently reported in the literature. The main characteristics of the syndrome are GDD/ID in 98\\% of patients, microcephaly in 65\\%, feeding difficulties in 62\\%, ADHD or hyperactivity in 54\\%, and autistic traits in 52\\%. Finally, using the location of 31 variants from the literature together with variants from the five patients, we found significantly higher ASSS values in patients with pathogenic variants affecting the 3′ end of the gene, confirming the genotype-phenotype correlation initially described.},\n\tlanguage = {en},\n\tnumber = {9},\n\turldate = {2021-09-07},\n\tjournal = {Genes},\n\tauthor = {Sanchez-Jimeno, Carolina and Blanco-Kelly, Fiona and López-Grondona, Fermina and Losada-Del Pozo, Rebeca and Moreno, Beatriz and Rodrigo-Moreno, María and Martinez-Cayuelas, Elena and Riveiro-Alvarez, Rosa and Fenollar-Cortés, María and Ayuso, Carmen and Rodríguez de Alba, Marta and Lorda-Sanchez, Isabel and Almoguera, Berta},\n\tmonth = aug,\n\tyear = {2021},\n\tnote = {Number: 9\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {ADHD, AUTS2, AUTS2 syndrome, autism, neurodevelopmental disorder},\n\tpages = {1360},\n}\n\n

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\n \n\n \n \n \n \n \n \n A novel homozygous mutation in the human ALG12 gene results in an aberrant profile of oligomannose N-glycans in patient's serum.\n \n \n \n \n\n\n \n Ziburová, J.; Nemčovič, M.; Šesták, S.; Bellová, J.; Pakanová, Z.; Siváková, B.; Šalingová, A.; Šebová, C.; Ostrožlíková, M.; Lekka, D.; Brucknerová, J.; Brucknerová, I.; Skokňová, M.; Cullough, A. M.; Hrčková, G.; Hlavatá, A.; Bzdúch, V.; Mucha, J.; and Baráth, P.\n\n\n \n\n\n\n American Journal of Medical Genetics Part A, n/a(n/a). September 2021.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajmg.a.62474\n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{ziburova_novel_2021,\n\ttitle = {A novel homozygous mutation in the human {ALG12} gene results in an aberrant profile of oligomannose {N}-glycans in patient's serum},\n\tvolume = {n/a},\n\tissn = {1552-4833},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.62474},\n\tdoi = {10.1002/ajmg.a.62474},\n\tabstract = {Congenital disorder of glycosylation type Ig (ALG12-CDG) is a rare inherited metabolic disease caused by a defect in alpha-mannosyltransferase 8, encoded by the ALG12 gene (22q13.33). To date, only 15 patients have been diagnosed with ALG12-CDG globally. Due to a newborn Slovak patient's clinical and biochemical abnormalities, the isoelectric focusing of transferrin was performed with observed significant hypoglycosylation typical of CDG I. Furthermore, analysis of neutral serum N-glycans by mass spectrometry revealed the accumulation of GlcNAc2Man5–7 and decreased levels of GlcNAc2Man8–9, which indicated impaired ALG12 enzymatic activity. Genetic analysis of the coding regions of the ALG12 gene of the patient revealed a novel homozygous substitution mutation c.1439T{\\textgreater}C p.(Leu480Pro) within Exon 10. Furthermore, both of the patient's parents and his twin sister were asymptomatic heterozygous carriers of the variant. This comprehensive genomic and glycomic approach led to the confirmation of the ALG12 pathogenic variant responsible for the clinical manifestation of the disorder in the patient described.},\n\tlanguage = {en},\n\tnumber = {n/a},\n\turldate = {2021-09-07},\n\tjournal = {American Journal of Medical Genetics Part A},\n\tauthor = {Ziburová, Jana and Nemčovič, Marek and Šesták, Sergej and Bellová, Jana and Pakanová, Zuzana and Siváková, Barbara and Šalingová, Anna and Šebová, Claudia and Ostrožlíková, Mária and Lekka, Dimitra-Evanthia and Brucknerová, Jana and Brucknerová, Ingrid and Skokňová, Martina and Cullough, Alexandra Mc and Hrčková, Gabriela and Hlavatá, Anna and Bzdúch, Vladimír and Mucha, Ján and Baráth, Peter},\n\tmonth = sep,\n\tyear = {2021},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajmg.a.62474},\n\tkeywords = {ALG12-CDG, CDG Ig, Clinical Exome, N-glycans, SOPHiA DDM, clinical exome sequencing},\n}\n\n

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\n \n\n \n \n \n \n \n \n Non-functional alternative splicing caused by a Latino pathogenic variant in a case of PMM2-CDG.\n \n \n \n \n\n\n \n González-Domínguez, C. A.; Villarroel, C. E.; Rodríguez-Morales, M.; Manrique-Hernández, S.; González-Jaimes, A.; Olvera-Rodriguez, F.; Beutelspacher, K.; Molina-Garay, C.; Carrillo-Sánchez, K.; Flores-Lagunes, L. L.; Jiménez-Olivares, M.; Muñoz-Rivas, A.; Cruz-Muñoz, M. E.; Mora-Montes, H. M.; Salinas-Marín, R.; Alaez-Verson, C.; and Martínez-Duncker, I.\n\n\n \n\n\n\n Molecular Genetics and Metabolism Reports, 28: 100781. July 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Non-functional$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{gonzalez-dominguez_non-functional_2021,\n\ttitle = {Non-functional alternative splicing caused by a {Latino} pathogenic variant in a case of {PMM2}-{CDG}},\n\tvolume = {28},\n\tissn = {2214-4269},\n\turl = {https://www.sciencedirect.com/science/article/pii/S2214426921000756},\n\tdoi = {10.1016/j.ymgmr.2021.100781},\n\tabstract = {We report on a Mexican mestizo with a multisystemic syndrome including neurological involvement and a type I serum transferrin isoelectric focusing (Tf IEF) pattern. Diagnosis of PMM2-CDG was obtained by clinical exome sequencing (CES) that revealed compound heterozygous variants in PMM2, the encoding gene for the phosphomannomutase 2 (PMM2). This enzyme catalyzes the conversion of mannose-6-P to mannose-1-P required for the synthesis of GDP-Man and Dol-P-Man, donor substrates for glycosylation reactions. The identified variants were c.422G{\\textgreater}A (R141H) and c.178G{\\textgreater}T, the former being the most frequent PMM2 pathogenic mutation and the latter a previously uncharacterized variant restricted to the Latino population with conflicting interpretations of pathogenicity and that we here report causes leaky non-functional alternative splicing (p.V60Cfs*3).},\n\tlanguage = {en},\n\turldate = {2021-08-30},\n\tjournal = {Molecular Genetics and Metabolism Reports},\n\tauthor = {González-Domínguez, C. A. and Villarroel, C. E. and Rodríguez-Morales, M. and Manrique-Hernández, S. and González-Jaimes, A. and Olvera-Rodriguez, F. and Beutelspacher, K. and Molina-Garay, C. and Carrillo-Sánchez, K. and Flores-Lagunes, L. L. and Jiménez-Olivares, M. and Muñoz-Rivas, A. and Cruz-Muñoz, M. E. and Mora-Montes, H. M. and Salinas-Marín, R. and Alaez-Verson, C. and Martínez-Duncker, I.},\n\tmonth = jul,\n\tyear = {2021},\n\tkeywords = {CES v2, SOPHiA DDM},\n\tpages = {100781},\n}\n\n

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\n \n\n \n \n \n \n \n \n Hb Tacoma: G\\textgreaterT or G\\textgreaterC, and Does It Matter?.\n \n \n \n \n\n\n \n Moore, J. A.; Pullon, B. M.; Wang, D.; and Brennan, S. O.\n\n\n \n\n\n\n Hemoglobin, 45(3): 203–206. July 2021.\n Publisher: Taylor & Francis _eprint: https://doi.org/10.1080/03630269.2021.1950010\n\n\n\n
\n\n\n\n \n \n $\"Hb$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{moore_hb_2021,\n\ttitle = {Hb {Tacoma}: {G}{\\textgreater}{T} or {G}{\\textgreater}{C}, and {Does} {It} {Matter}?},\n\tvolume = {45},\n\tissn = {0363-0269},\n\tshorttitle = {Hb {Tacoma}},\n\turl = {https://doi.org/10.1080/03630269.2021.1950010},\n\tdoi = {10.1080/03630269.2021.1950010},\n\tabstract = {Hb Tacoma [β30(B12)Arg→Ser] is a missense variant that is caused by either an AGG{\\textgreater}AGT or AGG{\\textgreater}AGC substitution at codon 30 of the HBB gene. Currently, the latter is classified as a rare cause of β0-thalassemia (β0-thal). We propose that HBB: c.93G{\\textgreater}C has been incorrectly assigned as β0-thal and discuss whether HBB: c.93G{\\textgreater}T or HBB: c.93G{\\textgreater}C should be classified as β+-thal instead, or as β-globin variants without thalassemic effect. We present several subjects who are heterozygous for Hb Tacoma, one with HBB: c.93G{\\textgreater}T and two with HBB: c.93G{\\textgreater}C, to support our conclusions.},\n\tnumber = {3},\n\turldate = {2021-08-30},\n\tjournal = {Hemoglobin},\n\tauthor = {Moore, Jordyn A. and Pullon, Beverley M. and Wang, Darrell and Brennan, Stephen O.},\n\tmonth = jul,\n\tyear = {2021},\n\tpmid = {34233561},\n\tnote = {Publisher: Taylor \\& Francis\n\\_eprint: https://doi.org/10.1080/03630269.2021.1950010},\n\tkeywords = {Alamut, Hb Tacoma, capillary electrophoresis (CE), splicing, time-of-flight (TOF) mass spectrometry (MS), β0-Thalassemia (β0-thal)},\n\tpages = {203--206},\n}\n\n

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\n \n\n \n \n \n \n \n Hereditary spastic paraplegia: new insights into clinical variability and spasticity-ataxia phenotype, and novel mutations.\n \n \n \n\n\n \n Sahin, I.; and Saat, H.\n\n\n \n\n\n\n Acta Neurologica Belgica. August 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{sahin_hereditary_2021,\n\ttitle = {Hereditary spastic paraplegia: new insights into clinical variability and spasticity-ataxia phenotype, and novel mutations},\n\tissn = {2240-2993},\n\tshorttitle = {Hereditary spastic paraplegia},\n\tdoi = {10.1007/s13760-021-01779-y},\n\tabstract = {INTRODUCTION: Hereditary spastic paraplegias (HSPs), a genetically heterogeneous group of neurodegenerative diseases, have an incidence of around 3 to 9 individuals every 100,000. Due to the broad clinical and genetic variability of HSPs, it is challenging to diagnose the disorder quickly and precisely. Hereditary spastic ataxias (HSAs) and HSPs are overlapping diseases, and their intersection has been gradually identified by next-generation sequencing. The idea of the spasticity-ataxia phenotype (SAP) spectrum is further substantiated by the similarities in phenotypes and underlying genes in ataxias and inherited spastic paraplegias and the related cellular processes and disease mechanisms these disorders exhibit.\nMETHODS: Whole-exome sequencing was performed on the 25 spastic or spastic-ataxic gait patients.\nRESULTS: Twenty-two specific HSPs-HSAs-SAP mutations, including 14 novel mutations, were found in 25 cases from 18 Turkish and 2 Syrian families. This research discovers many novel hereditary spastic paraplegia (HSP) mutations and shows a robust genotype-phenotype heterogeneity in the disease.\nCONCLUSIONS: This research helped expand the clinical and molecular scope of HSP and clarified the concept of the spasticity-ataxia phenotype, further enhancing our understanding of the complicated form of HSP and its association with ataxia. Our data broadens the spectrum of HSPs and HSAs related gene mutations and provides insights for genotype-phenotype correlations for HSPs and HSAs.},\n\tlanguage = {eng},\n\tjournal = {Acta Neurologica Belgica},\n\tauthor = {Sahin, Ibrahim and Saat, Hanife},\n\tmonth = aug,\n\tyear = {2021},\n\tpmid = {34420199},\n\tkeywords = {Hereditary spastic ataxia, Hereditary spastic paraplegia, NGS, SOPHiA DDM, Spasticity–ataxia phenotype},\n}\n\n

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\n \n\n \n \n \n \n \n \n Catch-up growth and discontinuation of fludrocortisone treatment in aldosterone synthase deficiency.\n \n \n \n \n\n\n \n Gurpinar Tosun, B.; Kendir Demirkol, Y.; Seven Menevse, T.; Kaygusuz, S. B.; Ozbek, M. N.; Altincik, S. A.; Mammadova, J.; Cayir, A.; Doger, E.; Bayramoglu, E.; Nalbantoglu, O.; Yesiltepe Mutlu, G.; Aghayev, A.; Turan, S.; Bereket, A.; and Guran, T.\n\n\n \n\n\n\n The Journal of Clinical Endocrinology & Metabolism, (dgab619). August 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Catch-up$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{gurpinar_tosun_catch-up_2021,\n\ttitle = {Catch-up growth and discontinuation of fludrocortisone treatment in aldosterone synthase deficiency},\n\tissn = {0021-972X},\n\turl = {https://doi.org/10.1210/clinem/dgab619},\n\tdoi = {10.1210/clinem/dgab619},\n\tabstract = {Aldosterone synthase deﬁciency (ASD) caused by mutations in the CYP11B2 gene is characterized by isolated mineralocorticoid deficiency. Data are scarce regarding clinical and biochemical outcomes of the disease in the follow-up.Assessment of the growth and steroid profiles of patients with ASD at the time of diagnosis and after discontinuation of treatment.Children with clinical diagnosis of ASD were included in a multicenter study. Growth and treatment characteristics were recorded. Plasma adrenal steroids were measured using liquid chromatography-mass spectrometry. Genetic diagnosis was confirmed by CYP11B2 gene sequencing and in silico analyses.Results: Sixteen patients from 12 families were included (8 females; median age at presentation:3.1 months, range:0.4-8.1). The most common symptom was poor weight gain (56.3\\%).Median age of onset of fludrocortisone treatment was 3.6 months (0.9-8.3). Catch-up growth was achieved at median 2 months (0.5-14.5) after treatment. Fludrocortisone could be stopped in five patients at a median age of 6.0 years (2.2-7.6). Plasma steroid profiles revealed reduced aldosterone synthase activity both at diagnosis and after discontinuation of treatment compared to age-matched controls.We identified six novel (p.Y195H, c.1200 + 1G\\&gt;A, p.F130L, p.E198del, c.1122-18G\\&gt;A, p.I339\\_E343del) and four previously described CYP11B2 variants. The most common variant was p.T185I (40\\%).Fludrocortisone treatment is associated with a rapid catch-up growth and control of electrolyte imbalances in ASD. Decreased mineralocorticoid requirement over time can be explained by the development of physiological adaptation mechanisms rather than improved aldosterone synthase activity. As complete biochemical remission cannot be achieved, a long-term surveillance of these patients is required.},\n\tnumber = {dgab619},\n\turldate = {2021-08-30},\n\tjournal = {The Journal of Clinical Endocrinology \\& Metabolism},\n\tauthor = {Gurpinar Tosun, Busra and Kendir Demirkol, Yasemin and Seven Menevse, Tuba and Kaygusuz, Sare Betul and Ozbek, Mehmet Nuri and Altincik, Selda Ayca and Mammadova, Jamala and Cayir, Atilla and Doger, Esra and Bayramoglu, Elvan and Nalbantoglu, Ozlem and Yesiltepe Mutlu, Gul and Aghayev, AghaRza and Turan, Serap and Bereket, Abdullah and Guran, Tulay},\n\tmonth = aug,\n\tyear = {2021},\n\tkeywords = {Clinical Exome, SOPHiA DDM},\n}\n\n

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\n \n\n \n \n \n \n \n \n Chromosomal microarray and exome sequencing in unexplained early infantile epileptic encephalopathies in a highly consanguineous population.\n \n \n \n \n\n\n \n Turkdogan, D.; Turkyilmaz, A.; Sager, G.; Ozturk, G.; Unver, O.; and Say, M.\n\n\n \n\n\n\n International Journal of Neuroscience, 0(0): 1–18. August 2021.\n Publisher: Taylor & Francis _eprint: https://doi.org/10.1080/00207454.2021.1967349\n\n\n\n
\n\n\n\n \n \n $\"Chromosomal$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{turkdogan_chromosomal_2021,\n\ttitle = {Chromosomal microarray and exome sequencing in unexplained early infantile epileptic encephalopathies in a highly consanguineous population},\n\tvolume = {0},\n\tissn = {0020-7454},\n\turl = {https://doi.org/10.1080/00207454.2021.1967349},\n\tdoi = {10.1080/00207454.2021.1967349},\n\tabstract = {Aim To identify genetic causes for early infantile epileptic encephalopathies (EIEE) in Turkish children with mostly consanguineous parents.Methods In a selected EIEE group (N = 59) based on results of nongenetic and initial genetic testing with unexplained etiology, 49 patients underwent array-based comparative genomic hybridization (aCGH) and 49 patients underwent whole exome sequencing (WES) including 39 with negative aCGH results and 10 with WES-only.Results Diagnostic yield of aCGH and WES for pathogenic or likely pathogenic variants was 14.3\\% and 38.8\\%, respectively. Including de novo variants of uncertain significance linked to compatible phenotypes, increased the diagnostic yield of WES to 61.2\\%. Out of 38 positive variants, 18 (47.4\\%) were novel and 16 (42.1\\%) were de novo. Twenty-one (56.8\\%) patients had recessive variants inherited from mostly consanguineous healthy parents (85.7\\%). Fourteen (37.8\\%) of patients with diagnostic results had positive variants in established EIEE genes. Seizures started during neonatal period in 32.4\\% patients. Posture or movement disorders were comorbid with EIEE in 40.5\\% of diagnosed patients. We identified treatable metabolic disorders in 8.1\\% of patients and pathogenic variants in genes which support using targeted medicine in 19\\% of patients.Conclusions Detailed electro-clinical phenotyping led to expansion of some of the known phenotypes with non-neurological and neurological findings in addition to seizures, as well as suggestion of candidate genes (SEC24B, SLC16A2 and PRICKLE2) and a copy number variant (microduplication of Xp21.1p11.4). The high ratio of recessive inheritance could be important for family counseling.},\n\tnumber = {0},\n\turldate = {2021-08-25},\n\tjournal = {International Journal of Neuroscience},\n\tauthor = {Turkdogan, Dilsad and Turkyilmaz, Ayberk and Sager, Gunes and Ozturk, Gulten and Unver, Olcay and Say, Merve},\n\tmonth = aug,\n\tyear = {2021},\n\tpmid = {34380004},\n\tnote = {Publisher: Taylor \\& Francis\n\\_eprint: https://doi.org/10.1080/00207454.2021.1967349},\n\tkeywords = {Early infantile epileptic encephalopathies, SOPHiA DDM, candidate genes, chromosomal microarray, recessive inheritance, targeted therapy, whole exome sequencing},\n\tpages = {1--18},\n}\n\n

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\n \n\n \n \n \n \n \n Early Start of Oral Clarithromycin Is Associated with Better Outcome in COVID-19 of Moderate Severity: The ACHIEVE Open-Label Single-Arm Trial.\n \n \n \n\n\n \n Tsiakos, K.; Tsakiris, A.; Tsibris, G.; Voutsinas, P.; Panagopoulos, P.; Kosmidou, M.; Petrakis, V.; Gravvani, A.; Gkavogianni, T.; Klouras, E.; Katrini, K.; Koufargyris, P.; Rapti, I.; Karageorgos, A.; Vrentzos, E.; Damoulari, C.; Zarkada, V.; Sidiropoulou, C.; Artemi, S.; Ioannidis, A.; Papapostolou, A.; Michelakis, E.; Georgiopoulou, M.; Myrodia, D.; Tsiamalos, P.; Syrigos, K.; Chrysos, G.; Nitsotolis, T.; Milionis, H.; Poulakou, G.; and Giamarellos-Bourboulis, E. J.\n\n\n \n\n\n\n Infectious Diseases and Therapy. August 2021.\n \n\n\n\n
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@article{tsiakos_early_2021,\n\ttitle = {Early {Start} of {Oral} {Clarithromycin} {Is} {Associated} with {Better} {Outcome} in {COVID}-19 of {Moderate} {Severity}: {The} {ACHIEVE} {Open}-{Label} {Single}-{Arm} {Trial}},\n\tissn = {2193-8229},\n\tshorttitle = {Early {Start} of {Oral} {Clarithromycin} {Is} {Associated} with {Better} {Outcome} in {COVID}-19 of {Moderate} {Severity}},\n\tdoi = {10.1007/s40121-021-00505-8},\n\tabstract = {INTRODUCTION: The anti-inflammatory effect of macrolides prompted the study of oral clarithromycin in moderate COVID-19.\nMETHODS: An open-label non-randomized trial in 90 patients with COVID-19 of moderate severity was conducted between May and October 2020. The primary endpoint was defined at the end of treatment (EOT) as no need for hospital re-admission and no progression into lower respiratory tract infection (LRTI) for patients with upper respiratory tract infection and as at least 50\\% decrease of the respiratory symptoms score without progression into severe respiratory failure (SRF) for patients with LRTI. Viral load, biomarkers, the function of mononuclear cells and safety were assessed.\nRESULTS: The primary endpoint was attained in 86.7\\% of patients treated with clarithromycin (95\\% CIs 78.1-92.2\\%); this was 91.7\\% and 81.4\\% among patients starting clarithromycin the first 5 days from symptoms onset or later (odds ratio after multivariate analysis 6.62; p 0.030). The responses were better for patients infected by non-B1.1 variants. Clarithromycin use was associated with decreases in circulating C-reactive protein, tumour necrosis factor-alpha and interleukin (IL)-6; by increase of production of interferon-gamma and decrease of production of interleukin-6 by mononuclear cells; and by suppression of SARS-CoV-2 viral load. No safety concerns were reported.\nCONCLUSIONS: Early clarithromycin treatment provides most of the clinical improvement in moderate COVID-19.\nTRIAL REGISTRATION: ClinicalTrials.gov, NCT04398004.},\n\tlanguage = {eng},\n\tjournal = {Infectious Diseases and Therapy},\n\tauthor = {Tsiakos, Konstantinos and Tsakiris, Antonios and Tsibris, Georgios and Voutsinas, Pantazis-Michael and Panagopoulos, Periklis and Kosmidou, Maria and Petrakis, Vasileios and Gravvani, Areti and Gkavogianni, Theologia and Klouras, Eleftherios and Katrini, Konstantina and Koufargyris, Panagiotis and Rapti, Iro and Karageorgos, Athanassios and Vrentzos, Emmanouil and Damoulari, Christina and Zarkada, Vagia and Sidiropoulou, Chrysanthi and Artemi, Sofia and Ioannidis, Anastasios and Papapostolou, Androniki and Michelakis, Evangelos and Georgiopoulou, Maria and Myrodia, Dimitra-Melia and Tsiamalos, Panteleimon and Syrigos, Konstantinos and Chrysos, George and Nitsotolis, Thomas and Milionis, Haralampos and Poulakou, Garyphallia and Giamarellos-Bourboulis, Evangelos J.},\n\tmonth = aug,\n\tyear = {2021},\n\tpmid = {34363189},\n\tpmcid = {PMC8345236},\n\tkeywords = {COVID-19, Clarithromycin, Clinical study, SARS-CoV-2, SOPHiA DDM, Th1, Th2, Viral load, clinical trial},\n}\n\n

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\n \n\n \n \n \n \n \n Wilms tumour occurring in a patient with osteopathia striata with cranial sclerosis: A still unsolved biological question.\n \n \n \n\n\n \n Quarello, P.; Perotti, D.; Carli, D.; Giorgio, E.; Sirchia, F.; Brusco, A.; Ferrero, G. B.; Mussa, A.; Spadea, M.; Ciceri, S.; Spreafico, F.; and Fagioli, F.\n\n\n \n\n\n\n Pediatric Blood & Cancer, 68(9): e29132. September 2021.\n \n\n\n\n
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@article{quarello_wilms_2021,\n\ttitle = {Wilms tumour occurring in a patient with osteopathia striata with cranial sclerosis: {A} still unsolved biological question},\n\tvolume = {68},\n\tissn = {1545-5017},\n\tshorttitle = {Wilms tumour occurring in a patient with osteopathia striata with cranial sclerosis},\n\tdoi = {10.1002/pbc.29132},\n\tlanguage = {eng},\n\tnumber = {9},\n\tjournal = {Pediatric Blood \\& Cancer},\n\tauthor = {Quarello, Paola and Perotti, Daniela and Carli, Diana and Giorgio, Elisa and Sirchia, Fabio and Brusco, Alfredo and Ferrero, Giovanni Battista and Mussa, Alessandro and Spadea, Manuela and Ciceri, Sara and Spreafico, Filippo and Fagioli, Franca},\n\tmonth = sep,\n\tyear = {2021},\n\tpmid = {34028980},\n\tkeywords = {clinical exome sequencing},\n\tpages = {e29132},\n}\n\n

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\n \n\n \n \n \n \n \n Investigation of genotype-phenotype relationship in Turkish patients with inherited retinal disease by next generation sequencing.\n \n \n \n\n\n \n Duzkale, N.; and Arslan, U.\n\n\n \n\n\n\n Ophthalmic Genetics,1–11. July 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{duzkale_investigation_2021,\n\ttitle = {Investigation of genotype-phenotype relationship in {Turkish} patients with inherited retinal disease by next generation sequencing},\n\tissn = {1744-5094},\n\tdoi = {10.1080/13816810.2021.1952616},\n\tabstract = {BACKGROUND: Inherited retinal dystrophies (IRDs) are a group of retinal diseases genetically and clinically highly heterogeneous and associated with more than 300 genes. This study aims to investigate the genetic basis of Turkish patients with IRDs.\nMATERIALS AND METHODS: In the study, genes related to retinal diseases in 86 IRDs patients were analyzed using the Next Generations Sequencing method (NGS).\nRESULTS: The mean age of 86 patients was 35 and the mean age at diagnosis was 18. There was consanguinity between the parents of 62\\% of these patients. Fifty-six retinal disease-associated genes of 46 patients and 230 retinal disease-associated genes of 40 patients were examined. Genetic analysis provides a molecular diagnosis in a total of 53 (61.6\\%) patients. The genes responsible for the IRDs phenotype were frequently identified as ABCA4 (25\\%), EYS (11\\%), and RDH12 (9\\%). There was no significant difference between those with and without a molecular diagnosis in terms of demographic characteristics and family history.\nCONCLUSIONS: Determination of genetic cause by NGS method in IRDs subgroups that are difficult to define by ophthalmic examination ensures that patients receive accurate diagnosis, treatment and counseling. This study contributed to the understanding of the genotype-phenotype relationship of Turkish patients with IRDs.},\n\tlanguage = {eng},\n\tjournal = {Ophthalmic Genetics},\n\tauthor = {Duzkale, Neslihan and Arslan, Umut},\n\tmonth = jul,\n\tyear = {2021},\n\tpmid = {34315337},\n\tkeywords = {HDS, Hereditary Disorder Solution, Hereditary Disorders, Inherited retinal dystrophies, gene, inheritance pattern, next-generation sequencing, variant type},\n\tpages = {1--11},\n}\n\n

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\n \n\n \n \n \n \n \n \n A Novel Homozygous ALG12 Mutation in a Patient with CDG Type Ig: New Report of a Case with a Mild Phenotype.\n \n \n \n \n\n\n \n Nicotera, A. G.; Spoto, G.; Calì, F.; Romeo, G.; Musumeci, A.; Vinci, M.; Fiumara, A.; Barone, R.; Rosa, G. D.; and Musumeci, S. A.\n\n\n \n\n\n\n Molecular Syndromology, 12(5): 327–332. July 2021.\n Publisher: Karger Publishers\n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{nicotera_novel_2021,\n\ttitle = {A {Novel} {Homozygous} {ALG12} {Mutation} in a {Patient} with {CDG} {Type} {Ig}: {New} {Report} of a {Case} with a {Mild} {Phenotype}},\n\tvolume = {12},\n\tissn = {1661-8769, 1661-8777},\n\tshorttitle = {A {Novel} {Homozygous} {ALG12} {Mutation} in a {Patient} with {CDG} {Type} {Ig}},\n\turl = {https://www.karger.com/Article/FullText/516606},\n\tdoi = {10.1159/000516606},\n\tabstract = {Congenital disorders of glycosylation (CDG) are a group of rare genetic diseases caused by the deficiency of enzymes involved in the biosynthesis or remodeling of the glycan moieties of glycoconjugates. Most of CDG are autosomal recessive; however, few of them show autosomal dominant or X-linked inheritance. ALG12-CDG is an autosomal recessive inherited defect caused by a deficiency in the α-mannosyltransferase, dolichyl-P-mannose: Man7-GlcNAc-2-PP-dolichyl-alpha-6-mannosyltransferase (mannosyltransferase 8), which determines Man7GlcNAc2-PP-dolichol accumulation in tissues including fibroblasts. The clinical features of ALG12-CDG include dysmorphic features, developmental delay, hypotonia, progressive microcephaly, hypogammaglobulinemia, coagulopathies, and failure to thrive. Herein, we describe the case of a Sicilian patient with a milder phenotype bearing an \\textit{ALG12} homozygous mutation. To date, including this patient, only 16 cases have been described with this form of CDG. Furthermore, our study contributes to understanding the milder ALG12-CDG cases and to further expanding the genotype-phenotype spectrum.},\n\tlanguage = {english},\n\tnumber = {5},\n\turldate = {2021-08-25},\n\tjournal = {Molecular Syndromology},\n\tauthor = {Nicotera, Antonio Gennaro and Spoto, Giulia and Calì, Francesco and Romeo, Giusi and Musumeci, Antonino and Vinci, Mirella and Fiumara, Agata and Barone, Rita and Rosa, Gabriella Di and Musumeci, Sebastiano Antonino},\n\tmonth = jul,\n\tyear = {2021},\n\tnote = {Publisher: Karger Publishers},\n\tkeywords = {CES},\n\tpages = {327--332},\n}\n\n

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\n \n\n \n \n \n \n \n \n Autophagy and Mitophagy-Related Pathways at the Crossroads of Genetic Pathways Involved in Familial Sarcoidosis and Host-Pathogen Interactions Induced by Coronaviruses.\n \n \n \n \n\n\n \n Pacheco, Y.; Valeyre, D.; El Jammal, T.; Vallee, M.; Chevalier, F.; Lamartine, J.; Sigaudo-Roussel, D.; Verrier, B.; Israel-Biet, D.; Freymond, N.; Cottin, V.; and Calender, A.\n\n\n \n\n\n\n Cells, 10(8): 1995. August 2021.\n Number: 8 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Autophagy$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{pacheco_autophagy_2021,\n\ttitle = {Autophagy and {Mitophagy}-{Related} {Pathways} at the {Crossroads} of {Genetic} {Pathways} {Involved} in {Familial} {Sarcoidosis} and {Host}-{Pathogen} {Interactions} {Induced} by {Coronaviruses}},\n\tvolume = {10},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\turl = {https://www.mdpi.com/2073-4409/10/8/1995},\n\tdoi = {10.3390/cells10081995},\n\tabstract = {Sarcoidosis is a multisystem disease characterized by the development and accumulation of granulomas, the hallmark of an inflammatory process induced by environmental and/or infectious and or genetic factors. This auto-inflammatory disease mainly affects the lungs, the gateway to environmental aggressions and viral infections. We have shown previously that genetic predisposition to sarcoidosis occurring in familial cases is related to a large spectrum of pathogenic variants with, however, a clustering around mTOR (mammalian Target Of Rapamycin)-related pathways and autophagy regulation. The context of the COVID-19 pandemic led us to evaluate whether such genetic defects may increase the risk of a severe course of SARS-CoV2 infection in patients with sarcoidosis. We extended a whole exome screening to 13 families predisposed to sarcoidosis and crossed the genes sharing mutations with the list of genes involved in the SARS-CoV2 host-pathogen protein-protein interactome. A similar analysis protocol was applied to a series of 100 healthy individuals. Using ENRICH.R, a comprehensive gene set enrichment web server, we identified the functional pathways represented in the set of genes carrying deleterious mutations and confirmed the overrepresentation of autophagy- and mitophagy-related functions in familial cases of sarcoidosis. The same protocol was applied to the set of genes common to sarcoidosis and the SARS-CoV2-host interactome and found a significant enrichment of genes related to mitochondrial factors involved in autophagy, mitophagy, and RIG-I-like (Retinoic Acid Inducible Gene 1) Receptor antiviral response signaling. From these results, we discuss the hypothesis according to which sarcoidosis is a model for studying genetic abnormalities associated with host response to viral infections as a consequence of defects in autophagy and mitophagy processes.},\n\tlanguage = {en},\n\tnumber = {8},\n\turldate = {2021-08-23},\n\tjournal = {Cells},\n\tauthor = {Pacheco, Yves and Valeyre, Dominique and El Jammal, Thomas and Vallee, Maxime and Chevalier, Fabien and Lamartine, Jérôme and Sigaudo-Roussel, Dominique and Verrier, Bernard and Israel-Biet, Dominique and Freymond, Nathalie and Cottin, Vincent and Calender, Alain},\n\tmonth = aug,\n\tyear = {2021},\n\tnote = {Number: 8\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Alamut, COVID-19, SARS-CoV2, TANK Binding Kinase 1, autophagy, genetics, mitophagy, sarcoidosis},\n\tpages = {1995},\n}\n\n

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\n \n\n \n \n \n \n \n \n Helicobacter pylori virulence factors and host genetic polymorphisms in a low gastric cancer incidence and high H pylori prevalence country.\n \n \n \n \n\n\n \n Rush, C. J.; Hoosien, E.; Villiers, N. d.; Clay, C.; Metz, D. C.; Setshedi, M.; Thomson, S. R.; and Levin, D. A.\n\n\n \n\n\n\n GastroHep, n/a(n/a). August 2021.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/ygh2.488\n\n\n\n
\n\n\n\n \n \n $\"Helicobacter$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{rush_helicobacter_2021,\n\ttitle = {Helicobacter pylori virulence factors and host genetic polymorphisms in a low gastric cancer incidence and high {H} pylori prevalence country},\n\tvolume = {n/a},\n\tissn = {1478-1239},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/ygh2.488},\n\tdoi = {10.1002/ygh2.488},\n\tabstract = {Background Helicobacter pylori virulence factors and host interleukin (IL) polymorphisms are implicated in the pathogenesis of gastric adenocarcinoma (GCA), but have not been investigated together, in the South African context of low GCA incidence and high H pylori prevalence. Aims To determine, based on these factors, the potential for developing GCA in a local cohort with H pylori-associated dyspepsia. Methods Seventy-nine patients underwent gastroscopy and biopsy. Helicobacter pylori-positive biopsies were analysed for virulence factors; cytotoxin-associated antigen (CagA) and vacuolating toxin (VacA) and mosaics (Vac A m1/m2, Vac A s1/s2 or combinations). Host DNA was analysed for targeted regions in IL-1B and IL-1RN genes, to determine polymorphisms of IL-1B-511*T and IL-1RN (variable number tandem repeat [VNTR]). Results The mean age was 43 years (SD ±11.7), 66\\% were female. Forty-eight patients (60\\%) were H pylori positive, 50\\% (24/48) demonstrated a virulent organism and 42\\% (20/48) of these demonstrated the most virulent carcinogenic combination; VacA m1/s1 and CagA. IL-1RN VNTR was sequenced in 25 specimens and IL-1B511 polymorphisms in 48 patients; the high-risk IL-1B511 TT allele was present in 52\\% (25/48) and TC allele in 33\\% (16/48). Overall, 85\\% (41/48) of patients demonstrated high-risk genetic polymorphisms. The highest risk associated with GCA, a combination of H pylori VacAm1/s1 virulence factor and IL-1B511 TT or TC allele, was demonstrated in 42\\% (20/48). Conclusion Almost half the patients have a combination of virulent H pylori and carcinogenic IL polymorphism. The implication of these observations on the risk of developing GCA requires further elucidation.},\n\tlanguage = {en},\n\tnumber = {n/a},\n\turldate = {2021-08-23},\n\tjournal = {GastroHep},\n\tauthor = {Rush, Colin J. and Hoosien, Ebrahim and Villiers, Nico de and Clay, Cornelis and Metz, David C. and Setshedi, Mashiko and Thomson, Sandie R. and Levin, Dion A.},\n\tmonth = aug,\n\tyear = {2021},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/ygh2.488},\n\tkeywords = {Alamut, disease-based H pylori, organ-based gastric cancer, stomach and duodenum, topics},\n}\n\n

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\n \n\n \n \n \n \n \n \n RBM20 mutation and ventricular arrhythmias in a young patient with dilated cardiomyopathy: a case report.\n \n \n \n \n\n\n \n Liatakis, I.; Prappa, E.; Gouziouta, A.; Pantou, M. P; Gourzi, P.; Vlachos, K.; Mililis, P.; Kariki, O.; Degiannis, D.; Efremidis, M.; and Letsas, K. P\n\n\n \n\n\n\n American Journal of Cardiovascular Disease, 11(3): 398–403. June 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"RBM20$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{liatakis_rbm20_2021,\n\ttitle = {{RBM20} mutation and ventricular arrhythmias in a young patient with dilated cardiomyopathy: a case report},\n\tvolume = {11},\n\tissn = {2160-200X},\n\tshorttitle = {{RBM20} mutation and ventricular arrhythmias in a young patient with dilated cardiomyopathy},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303033/},\n\tabstract = {Gene mutations in RBM20 have been identified in a minority of familial and sporadic dilated cardiomyopathy cases. Recent studies of carriers of RBM20 mutations not only highlight the aforementioned association with dilated cardiomyopathy but also indicate a link with increased incidence of ventricular arrhythmias. Herein we describe a case of 17-year-old female patient with dilated cardiomyopathy carrying a p.(Arg634Trp) RBM20 mutation and presenting with frequent premature ventricular contractions and episodes of non-sustained ventricular tachycardia.},\n\tnumber = {3},\n\turldate = {2021-08-06},\n\tjournal = {American Journal of Cardiovascular Disease},\n\tauthor = {Liatakis, Ioannis and Prappa, Efstathia and Gouziouta, Aggeliki and Pantou, Malena P and Gourzi, Polyxeni and Vlachos, Konstantinos and Mililis, Panagiotis and Kariki, Ourania and Degiannis, Dimitrios and Efremidis, Michael and Letsas, Konstantinos P},\n\tmonth = jun,\n\tyear = {2021},\n\tpmid = {34322310},\n\tpmcid = {PMC8303033},\n\tkeywords = {Cardiology, SOPHiA DDM, SOPHiA Extended Cardio Solution},\n\tpages = {398--403},\n}\n\n

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\n \n\n \n \n \n \n \n Current and Future Application of Artificial Intelligence in Clinical Medicine.\n \n \n \n\n\n \n Yang, J.; and Huang, S.\n\n\n \n\n\n\n Bentham Science Publishers, June 2021.\n Google-Books-ID: oAY5EAAAQBAJ\n\n\n\n
\n\n\n\n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@book{yang_current_2021,\n\ttitle = {Current and {Future} {Application} of {Artificial} {Intelligence} in {Clinical} {Medicine}},\n\tisbn = {978-1-68108-842-6},\n\tabstract = {Current and Future Application of Artificial Intelligence in Clinical Medicine presents updates on the application of machine learning and deep learning techniques in medical procedures. . Chapters in the volume have been written by outstanding contributors from cancer and computer science institutes with the goal of providing updated knowledge to the reader. Topics covered in the book include 1) Artificial Intelligence (AI) applications in cancer diagnosis and therapy, 2) Updates in AI applications in the medical industry, 3) the use of AI in studying the COVID-19 pandemic in China, 4) AI applications in clinical oncology (including AI-based mining for pulmonary nodules and the use of AI in understanding specific carcinomas), 5) AI in medical imaging. Each chapter presents information on related sub topics in a reader friendly format.The combination of expert knowledge and multidisciplinary approaches highlighted in the book make it a valuable source of information for physicians and clinical researchers active in the field of cancer diagnosis and treatment (oncologists, oncologic surgeons, radiation oncologists, nuclear medicine physicians, and radiologists) and computer science scholars seeking to understand medical applications of artificial intelligence.},\n\tlanguage = {en},\n\tpublisher = {Bentham Science Publishers},\n\tauthor = {Yang, Jie and Huang, Shigao},\n\tmonth = jun,\n\tyear = {2021},\n\tnote = {Google-Books-ID: oAY5EAAAQBAJ},\n\tkeywords = {Medical / Clinical Medicine},\n}\n\n

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\n \n\n \n \n \n \n \n \n Severe ulcerative proctitis, pyoderma gangrenosum, hidradenitis suppurativa and fever in a patient with a rare variant of the PSTPIP1 gene.\n \n \n \n \n\n\n \n Hieta, N.; Nuutinen, H.; Roivas, J.; Salminen, K.; Kujari, H.; Talve, L.; Toivonen, M.; and Haanpää, M. K.\n\n\n \n\n\n\n Clinical and Experimental Dermatology, n/a(n/a). July 2021.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/ced.14754\n\n\n\n
\n\n\n\n \n \n $\"Severe$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{hieta_severe_2021,\n\ttitle = {Severe ulcerative proctitis, pyoderma gangrenosum, hidradenitis suppurativa and fever in a patient with a rare variant of the {PSTPIP1} gene},\n\tvolume = {n/a},\n\tissn = {1365-2230},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1111/ced.14754},\n\tdoi = {10.1111/ced.14754},\n\tlanguage = {en},\n\tnumber = {n/a},\n\turldate = {2021-08-06},\n\tjournal = {Clinical and Experimental Dermatology},\n\tauthor = {Hieta, N. and Nuutinen, H. and Roivas, J. and Salminen, K. and Kujari, H. and Talve, L. and Toivonen, M. and Haanpää, M. K.},\n\tmonth = jul,\n\tyear = {2021},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/ced.14754},\n\tkeywords = {Custom, Custom Panel, SOPHiA DDM},\n}\n\n

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\n \n\n \n \n \n \n \n \n NGS Analysis of Liquid Biopsy (LB) and Formalin-Fixed Paraffin-Embedded (FFPE) Melanoma Samples Using Oncomine™ Pan-Cancer Cell-Free Assay.\n \n \n \n \n\n\n \n Olbryt, M.; Rajczykowski, M.; Bal, W.; Fiszer-Kierzkowska, A.; Cortez, A. J.; Mazur, M.; Suwiński, R.; and Widłak, W.\n\n\n \n\n\n\n Genes, 12(7): 1080. July 2021.\n Number: 7 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"NGS$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{olbryt_ngs_2021,\n\ttitle = {{NGS} {Analysis} of {Liquid} {Biopsy} ({LB}) and {Formalin}-{Fixed} {Paraffin}-{Embedded} ({FFPE}) {Melanoma} {Samples} {Using} {Oncomine}™ {Pan}-{Cancer} {Cell}-{Free} {Assay}},\n\tvolume = {12},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\turl = {https://www.mdpi.com/2073-4425/12/7/1080},\n\tdoi = {10.3390/genes12071080},\n\tabstract = {Next-generation sequencing (NGS) in liquid biopsies may contribute to the diagnosis, monitoring, and personalized therapy of cancer through the real-time detection of a tumor’s genetic profile. There are a few NGS platforms offering high-sensitivity sequencing of cell-free DNA (cfDNA) samples. The aim of this study was to evaluate the Ion AmpliSeq HD Technology for targeted sequencing of tumor and liquid biopsy samples from patients with fourth-stage melanoma. Sequencing of 30 samples (FFPE tumor and liquid biopsy) derived from 14 patients using the Oncomine™ Pan-Cancer Cell-Free Assay was performed. The analysis revealed high concordance between the qPCR and NGS results of the BRAF mutation in FFPE samples (91\\%), as well as between the FFPE and liquid biopsy samples (91\\%). The plasma-tumor concordance of the non-BRAF mutations was 28\\%. A total of 17 pathogenic variants in 14 genes (from 52-gene panel), including TP53, CTNNB1, CCND1, MET, MAP2K1, and GNAS, were identified, with the CTNNB1S45F variant being the most frequent. A positive correlation between the LDH level and cfDNA concentration as well as negative correlation between the LDH level and time to progression was confirmed in a 22-patient cohort. The analysis showed both the potential and limitations of liquid biopsy genetic profiling using HD technology and the Ion Torrent platform.},\n\tlanguage = {en},\n\tnumber = {7},\n\turldate = {2021-08-06},\n\tjournal = {Genes},\n\tauthor = {Olbryt, Magdalena and Rajczykowski, Marcin and Bal, Wiesław and Fiszer-Kierzkowska, Anna and Cortez, Alexander Jorge and Mazur, Magdalena and Suwiński, Rafał and Widłak, Wiesława},\n\tmonth = jul,\n\tyear = {2021},\n\tnote = {Number: 7\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Alamut, liquid biopsy, melanoma, targeted next-generation sequencing},\n\tpages = {1080},\n}\n\n

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\n \n\n \n \n \n \n \n \n Novel Mutation in CRYBB3 Causing Pediatric Cataract and Microphthalmia.\n \n \n \n \n\n\n \n Zin, O. A.; Neves, L. M.; Motta, F. L.; Horovitz, D. D. G.; Guida, L.; Gomes, L. H. F.; Cunha, D. P.; Rodrigues, A. P. S.; Zin, A. A.; Sallum, J. M. F.; and Vasconcelos, Z. F. M.\n\n\n \n\n\n\n Genes, 12(7): 1069. July 2021.\n Number: 7 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Novel$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{zin_novel_2021,\n\ttitle = {Novel {Mutation} in {CRYBB3} {Causing} {Pediatric} {Cataract} and {Microphthalmia}},\n\tvolume = {12},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\turl = {https://www.mdpi.com/2073-4425/12/7/1069},\n\tdoi = {10.3390/genes12071069},\n\tabstract = {Up to 25\\% of pediatric cataract cases are inherited, with half of the known mutant genes belonging to the crystallin family. Within these, crystallin beta B3 (CRYBB3) has the smallest number of reported variants. Clinical ophthalmological and genetic-dysmorphological evaluation were performed in three autosomal dominant family members with pediatric cataract and microphthalmia, as well as one unaffected family member. Peripheral blood was collected from all participating family members and next-generation sequencing was performed. Bioinformatics analysis revealed a novel missense variant c.467G\\&gt;A/p.Gly156Glu in CRYBB3 in all family members with childhood cataract. This variant is classified as likely pathogenic by ACMG, and no previous descriptions of it were found in ClinVar, HGMD or Cat-Map. The only other mutation previously described in the fifth exon of CRYBB3 is a missense variant that causes a change in amino acid from the same 156th amino acid to arginine and has been associated with pediatric cataract and microphthalmia. To the best of our knowledge, this is the first time the c.467G\\&gt;A/p.Gly156Glu variant is reported and the second time a mutation in CRYBB3 has been associated with microphthalmia.},\n\tlanguage = {en},\n\tnumber = {7},\n\turldate = {2021-08-05},\n\tjournal = {Genes},\n\tauthor = {Zin, Olivia A. and Neves, Luiza M. and Motta, Fabiana L. and Horovitz, Dafne D. G. and Guida, Leticia and Gomes, Leonardo H. F. and Cunha, Daniela P. and Rodrigues, Ana Paula S. and Zin, Andrea A. and Sallum, Juliana M. F. and Vasconcelos, Zilton F. M.},\n\tmonth = jul,\n\tyear = {2021},\n\tnote = {Number: 7\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {CES v2, Clinical Exome, Trio analysis, congenital cataract, genotype, microphthalmia, pediatric cataract, pediatric ophthalmology, phenotype},\n\tpages = {1069},\n}\n\n

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\n \n\n \n \n \n \n \n Internal Standardization of the Interpretation and Reporting of Sequence Variants in Hematologic Neoplasms.\n \n \n \n\n\n \n Mehta, N.; He, R.; and Viswanatha, D. S.\n\n\n \n\n\n\n Molecular Diagnosis & Therapy. June 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{mehta_internal_2021,\n\ttitle = {Internal {Standardization} of the {Interpretation} and {Reporting} of {Sequence} {Variants} in {Hematologic} {Neoplasms}},\n\tissn = {1179-2000},\n\tdoi = {10.1007/s40291-021-00540-8},\n\tabstract = {INTRODUCTION: Accurate classification of somatic genetic alterations detected by next-generation sequencing (NGS) assays is of paramount importance to ensure the provision of high-quality clinical data. Clinical significance of variants can be assessed and tiered based on guidelines from the Association for Molecular Pathology (AMP), the American Society of Clinical Oncology, and the College of American Pathology for the interpretation of somatic sequence variants identified in cancer.\nMETHODS: We sought to develop a formal structured approach for the classification of somatic variants in hematologic neoplasms, to account for both a variant's clinical significance and its ability to drive tumorigenesis, by adapting elements from these existing guidelines. However, we additionally utilized key criteria from the American College of Medical Genetics/AMP standards for variant reporting to focus evaluation into specific categories of evidence and to gauge the effect of a given variant on tumorigenesis.\nRESULTS: The combined approach was applied to the annotation of 87 variants identified by a targeted NGS panel for myeloid neoplasms. In the application of our variant evaluation, we classified 2/87 variants as benign, 6/87 as likely benign, 56/87 as variants of unknown significance (VUS), 13/87 variants as likely pathogenic, and 10/87 variants as pathogenic.\nCONCLUSION: Well-established oncogenic alterations were accurately classified as pathogenic. Although there is no defined benchmark for the remaining variants, drawing from two existing guidelines enabled the creation of a modified curation process for variant interpretation that emphasizes systematic review of relevant evidence.},\n\tlanguage = {eng},\n\tjournal = {Molecular Diagnosis \\& Therapy},\n\tauthor = {Mehta, Nikita and He, Rong and Viswanatha, David S.},\n\tmonth = jun,\n\tyear = {2021},\n\tpmid = {34125426},\n\tkeywords = {Alamut},\n}\n\n

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\n \n\n \n \n \n \n \n An attempt to dissect a peripheral marker based on cell pathology in Parkinson's disease.\n \n \n \n\n\n \n Biagioni, F.; Ferese, R.; Giorgi, F. S.; Modugno, N.; Olivola, E.; Lenzi, P.; Gambardella, S.; Centonze, D.; Ruggieri, S.; and Fornai, F.\n\n\n \n\n\n\n Journal of Neural Transmission (Vienna, Austria: 1996). June 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{biagioni_attempt_2021,\n\ttitle = {An attempt to dissect a peripheral marker based on cell pathology in {Parkinson}'s disease},\n\tissn = {1435-1463},\n\tdoi = {10.1007/s00702-021-02364-6},\n\tabstract = {Peripheral markers in Parkinson's disease (PD) represent a hot issue to provide early diagnosis and assess disease progression. The gold standard marker of PD should feature the same reliability as the pathogenic alteration, which produces the disease itself. PD is foremost a movement disorder produced by a loss of nigrostriatal dopamine innervation, in which striatal dopamine terminals are always markedly reduced in PD patients to an extent, which never overlaps with controls. Similarly, a reliable marker of PD should possess such a non-overlapping feature when compared with controls. In the present study, we provide a novel pathological hallmark, the autophagosome, which in each PD patient was always suppressed compared with each control subject. Autophagosomes were counted as microtubule-associated proteins 1A/1B light chain 3B (LC3)-positive vacuoles at ultrastructural morphometry within peripheral (blood) blood mononuclear cells (PBMC). This also provides the gold standard to assess the autophagy status. Since autophagy may play a role in the pathogenesis of PD, autophagosomes may be a disease marker, while participating in the biology of the disease. Stoichiometric measurement of α-synuclein despite significantly increased in PD patients, overlapped between PD and control patients. Although the study need to be validated in large populations, the number of autophagy vacuoles is neither related with therapy (the amount was similarly suppressed in a few de novo patients), nor the age in PD or controls.},\n\tlanguage = {eng},\n\tjournal = {Journal of Neural Transmission (Vienna, Austria: 1996)},\n\tauthor = {Biagioni, Francesca and Ferese, Rosangela and Giorgi, Filippo Sean and Modugno, Nicola and Olivola, Enrica and Lenzi, Paola and Gambardella, Stefano and Centonze, Diego and Ruggieri, Stefano and Fornai, Francesco},\n\tmonth = jun,\n\tyear = {2021},\n\tpmid = {34109443},\n\tkeywords = {Autophagy, CES, LC3, Parkinson’s disease, Peripheral blood mononuclear cells, SOPHiA DDM, Synuclein, Vacuoles},\n}\n\n

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\n \n\n \n \n \n \n \n A novel de novo NIPA1 missense mutation associated to hereditary spastic paraplegia.\n \n \n \n\n\n \n Fabbro, D.; Mio, C.; Fogolari, F.; and Damante, G.\n\n\n \n\n\n\n Journal of Human Genetics. June 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{fabbro_novel_2021,\n\ttitle = {A novel de novo {NIPA1} missense mutation associated to hereditary spastic paraplegia},\n\tissn = {1435-232X},\n\tdoi = {10.1038/s10038-021-00941-x},\n\tabstract = {SPG6 accounts for 1\\% of autosomal dominant Hereditary Spastic Paraplegia (HSP) and is caused by pathogenic variants in NIPA1, which encodes a magnesium transporter located in plasma membrane and early endosomes, implicated in neuronal development and maintenance. Here we report a 39-year-old woman affected by progressive gait disturbance associated to absence seizures episodes within childhood. Clinical exome sequencing identified a likely pathogenic de novo heterozygous variant in NIPA1 (NM\\_144599.5 c.249 C {\\textgreater} G; p.Asn83Lys). Molecular modelling was performed to evaluate putative functional consequence of the NIPA1 protein. Indeed, the Asn83Lys modification is predicted to induce a significant perturbation of the protein structure, altering signal transduction or small-molecule transport by modulating the length of the second transmembrane domain. This is the first study reporting a SPG6-affected patient harbouring the NIPA1 p.Asn83Lys mutation.},\n\tlanguage = {eng},\n\tjournal = {Journal of Human Genetics},\n\tauthor = {Fabbro, Dora and Mio, Catia and Fogolari, Federico and Damante, Giuseppe},\n\tmonth = jun,\n\tyear = {2021},\n\tpmid = {34108639},\n\tkeywords = {CES, Novel variant, novel mutation},\n}\n\n

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\n \n\n \n \n \n \n \n \n Very Low Vitamin D in a Patient with a Novel Pathogenic Variant in the GC Gene that encodes Vitamin D-Binding Protein.\n \n \n \n \n\n\n \n Banerjee, R. R; Spence, T.; Frank, S. J; Pandian, R.; Hoofnagle, A. N; Argiropoulos, B.; and Marcadier, J. L\n\n\n \n\n\n\n Journal of the Endocrine Society, (bvab104). June 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Very$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{banerjee_very_2021,\n\ttitle = {Very {Low} {Vitamin} {D} in a {Patient} with a {Novel} {Pathogenic} {Variant} in the {GC} {Gene} that encodes {Vitamin} {D}-{Binding} {Protein}},\n\tissn = {2472-1972},\n\turl = {https://doi.org/10.1210/jendso/bvab104},\n\tdoi = {10.1210/jendso/bvab104},\n\tabstract = {Circulating plasma vitamin D metabolites are highly bound to vitamin D-binding protein (DBP), also known as group-specific component or Gc-globulin. DBP, encoded by the GC gene, is a member of the albumin family of globular serum transport proteins. We previously described a homozygous GC gene deletion in a patient with apparent severe vitamin D deficiency, fragility fractures and ankylosing spondylitis. Here, we report an unrelated patient free of fractures or rheumatologic disease, but with very low 25-hydroxyvitamin D and 1,25-hydroxyvitamin D, as well as undetectable DBP measured by liquid chromatography-tandem mass spectrometry. A whole gene deletion was excluded by microarray, and Sanger sequencing of GC revealed a homozygous pathogenic variant affecting a canonical splice site (c.702-1G\\&gt;A). These findings indicate that loss of function variants in GC that eliminate DBP, and severely reduced total circulating vitamin D levels, do not necessarily result in significant metabolic bone disease. Together with our previous report, these cases support the free-hormone hypothesis, and suggest free vitamin D metabolites may serve as preferable indicators of bone and mineral metabolism, particularly when clinical suspicion of DBP deficiency is high.},\n\tnumber = {bvab104},\n\turldate = {2021-06-21},\n\tjournal = {Journal of the Endocrine Society},\n\tauthor = {Banerjee, Ronadip R and Spence, Tara and Frank, Stuart J and Pandian, Raj and Hoofnagle, Andrew N and Argiropoulos, Bob and Marcadier, Julien L},\n\tmonth = jun,\n\tyear = {2021},\n\tkeywords = {Alamut, Novel variant, novel mutation},\n}\n\n

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\n \n\n \n \n \n \n \n Spotted bones in an osteopoikilosis-related disease (Buschke Ollendorff Syndrome): Identifying this rare condition from the lab to the field.\n \n \n \n\n\n \n Zdral, S.; and Trujillo-Tiebas, M. J.\n\n\n \n\n\n\n International Journal of Paleopathology, 34: 20–28. June 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{zdral_spotted_2021,\n\ttitle = {Spotted bones in an osteopoikilosis-related disease ({Buschke} {Ollendorff} {Syndrome}): {Identifying} this rare condition from the lab to the field},\n\tvolume = {34},\n\tissn = {1879-9825},\n\tshorttitle = {Spotted bones in an osteopoikilosis-related disease ({Buschke} {Ollendorff} {Syndrome})},\n\tdoi = {10.1016/j.ijpp.2021.05.010},\n\tabstract = {OBJECTIVE: To improve the differential diagnosis of osteopoikilosis in past populations using a clinical case as an example of this rare condition.\nMATERIALS: A patient referred to our Genetic Service with suspected Buschke Ollendorff Syndrome after finding a connective nevus.\nMETHODS: Radiological images from different body regions were accompanied by a genetic study using next-generation sequencing.\nRESULTS: Small circular-to-ellipsoid sclerotic lesions were found in the epiphysis and metaphysis of long bones, as well as in the pelvis. These lesions were bilaterally distributed and with well-defined margins, compatible with the characteristics of Buschke Ollendorff Syndrome, bone manifestation osteopoikilosis. A heterozygous mutation on LEMD3 (NM\\_001167614:c.1918 + 1G {\\textgreater} C) was identified by next-generation sequencing. Based on this confirmed case, we have discussed the most probable causes of similar bone lesions found in the archaeological record.\nCONCLUSION: It has been demonstrated how a current case of a rare disease can provide useful tools to improve the differential diagnosis of this disease in ancient skeletons.\nSIGNIFICANCE: This work underlines the great need for multidisciplinary platforms that integrates clinical research into paleopathology in order to successfully address the study of rare diseases from the past.\nLIMITATIONS: Since OPK is only detected by X-rays, suspected cases of this bone lesion will only be identified when radiographs are taken for other purposes.\nSUGGESTIONS FOR FURTHER RESEARCH: Retrospective and large-scale studies of radiographs from other research in past populations.},\n\tlanguage = {eng},\n\tjournal = {International Journal of Paleopathology},\n\tauthor = {Zdral, Sofía and Trujillo-Tiebas, María José},\n\tmonth = jun,\n\tyear = {2021},\n\tpmid = {34098227},\n\tkeywords = {CES v2, Clinical case, Next-generation sequencing (NGS), Sclerosing bone dysplasia, X-rays},\n\tpages = {20--28},\n}\n\n

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\n \n\n \n \n \n \n \n \n First reported cases of SARS-CoV-2 sub-lineage B.1.617.2 in Brazil: an outbreak in a ship and alert for spread - SARS-CoV-2 coronavirus.\n \n \n \n \n\n\n \n \n\n\n \n\n\n\n May 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"First$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@misc{noauthor_first_2021,\n\ttitle = {First reported cases of {SARS}-{CoV}-2 sub-lineage {B}.1.617.2 in {Brazil}: an outbreak in a ship and alert for spread - {SARS}-{CoV}-2 coronavirus},\n\tshorttitle = {First reported cases of {SARS}-{CoV}-2 sub-lineage {B}.1.617.2 in {Brazil}},\n\turl = {https://virological.org/t/first-reported-cases-of-sars-cov-2-sub-lineage-b-1-617-2-in-brazil-an-outbreak-in-a-ship-and-alert-for-spread/706},\n\tabstract = {First reported cases of SARS-CoV-2 sub-lineage B.1.617.2 in Brazil: an outbreak in  a ship and alert for spread  Mirleide Cordeiro dos Santos 1, Edivaldo Costa Sousa Júnior 1, Jessylene de Almeida  Ferreira 1, Luana Soares Barbagelata 1, Sandro Patroca da Silva 2, Amanda Mendes Silva 1,  Jedson Cardoso 1, Rayssa Layna da Silva Bedran 1, Wanderley Dias das Chagas Junior 1,  Delana Andreza Melo Bezerra 1, Kenny da Costa Pinheiro 1, Dielle Teixeira Monteiro 1,  Patrícia dos Santos Lobo 1, Gabriela ...},\n\tlanguage = {en},\n\turldate = {2021-06-21},\n\tjournal = {Virological},\n\tmonth = may,\n\tyear = {2021},\n\tkeywords = {SARS-CoV-2, SOPHiA DDM},\n}\n\n

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\n \n\n \n \n \n \n \n Post-mortem Diagnosis of Pyruvate Carboxylase Deficiency by Exome Sequencing in a Family with three Deceased Children: A Case Report.\n \n \n \n\n\n \n Elalaoui, S. C.; Lyahyai, J.; Zrhidri, A.; Ratbi, I.; and Sefiani, A.\n\n\n \n\n\n\n Scholars Journal of Medical Case Reports,4. May 2021.\n \n\n\n\n
\n\n\n\n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{elalaoui_post-mortem_2021,\n\ttitle = {Post-mortem {Diagnosis} of {Pyruvate} {Carboxylase} {Deficiency} by {Exome} {Sequencing} in a {Family} with three {Deceased} {Children}: {A} {Case} {Report}},\n\tlanguage = {en},\n\tjournal = {Scholars Journal of Medical Case Reports},\n\tauthor = {Elalaoui, Siham Chafai and Lyahyai, Jaber and Zrhidri, Abdelali and Ratbi, Ilham and Sefiani, Abdelaziz},\n\tmonth = may,\n\tyear = {2021},\n\tkeywords = {CES},\n\tpages = {4},\n}\n\n

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\n \n\n \n \n \n \n \n \n MO046NGS PANEL PERFORMANCE IN THE DIAGNOSIS OF HEREDITARY RENAL DISEASE IN SOUTHERN SPAIN.\n \n \n \n \n\n\n \n Del Águila García, M. d. M.; Poyatos Andújar, A. M; Morales García, A. I.; Martínez Atienza, M.; García Linares, S.; and Esteban de la Rosa, R. J.\n\n\n \n\n\n\n Nephrology Dialysis Transplantation, 36(Supplement_1). May 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"MO046NGS$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 8 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{del_aguila_garcia_mo046ngs_2021,\n\ttitle = {{MO046NGS} {PANEL} {PERFORMANCE} {IN} {THE} {DIAGNOSIS} {OF} {HEREDITARY} {RENAL} {DISEASE} {IN} {SOUTHERN} {SPAIN}},\n\tvolume = {36},\n\tissn = {0931-0509},\n\turl = {https://doi.org/10.1093/ndt/gfab080.0018},\n\tdoi = {10.1093/ndt/gfab080.0018},\n\tabstract = {Hereditary renal disease (HRD) is still underdiagnosed: although we know aspects related to autosomal dominant polycystic kidney disease (ADPKD), we know little about the incidence and prevalence of other entities such as Alport syndrome. Altogether, HRD can represent 15\\% of individuals undergoing renal replacement therapy (RRT) or could even be higher.The advancement of genetics at the healthcare level let to achieve accurate and early renal diagnoses, as well as the incorporation of genetic counseling to families, all of which will result in better management of the disease in its initial stages and the possibility of offering reproductive options that avoid transmission to offspring.Our objective is to know the performance offered by the implementation of the ERH panel through Next Generation Sequencing (NGS) in our healthcare area.Observational-descriptive study of 259 probands (141 men / 118 women), mean age of 46 years (30 pediatric / 123 over 50 years), with chronic kidney disease and suspected hereditary cause attended in the specialized consultation of our centers from October 2018 to October 2020. The DNA extracted from leukocytes obtained by venipuncture was processed with Nephropathies Solution version 3 panel (SOPHiA Genetics) according to the manufacturer's protocol. This panel covers the coding regions and splicing junctions of 44 HRD-related genes such as nephrotic syndromes, polycystic kidney diseases, Bartter syndromes, Alport syndrome, CAKUT or tubulopathies (table 1).MO046 Table 1:Genes included in the SOPHiA Genetics Nephropaties solution panel.The sequencing of the libraries was done in a MiSeq (Illumina Inc), the bioinformatic analysis of the data and annotation of variants was performed using the SOPHiA DDM 5.8.0.3 software, and the revision of variants by consulting the main databases (ClinVar, Exac, HGMD, NCBI, PKD Foundation, LOVD).The panel was informative (pathogenic or probably pathogenic) in 80/259 patients (31\\%) and 56/259 cases (21.66\\%) of variants of uncertain significance (VSI) were detected.Autosomal dominant polycystic kidney disease accounted for 76.2\\% of the variants identified (56.2\\% PKD1, 20\\% PKD2), following Alport syndrome with 15\\% and the alterations in the PKHD1 gene associated with renal polycystic disease in its recessive form with about 4\\% (Figure 1). We have also identified a case of autosomal dominant tubulointerstitial kidney disease associated with the UMOD gene that was not suspected until the genetic study was performed. We highlight that 45\\% (36/80) of the variants identified as responsible for the renal disease are not yet described. Overall, the most prevalent type of mutation is that which produces displacement in the reading frame or frameshift (Figure 2). Individually, frameshift is the most frequent alteration in PKD1, PKD2 and COL4A5, while for PKHD1, COL4A3 and COL4A4 it is missense.MO046 Figure 2: Types of mutations according to frequency.Our NGS HRD panel a) offers an adequate diagnostic performance at the healthcare level, with definitive results in 1 out of 3 cases and has also allowed the performance of many carrier studies among family members b) is able of diagnosing the most frequent disease, ADPKD and Alport syndrome, as well as unresolved or poorly characterized cases, and c) opens the horizon for new diagnoses, all without increasing costs by outsourcing services. All this makes the genetic study of renal pathology a useful and efficient strategy.These results encourage us to enhance the resources in this area that we consider to be of strategic value.},\n\tnumber = {Supplement\\_1},\n\turldate = {2021-06-21},\n\tjournal = {Nephrology Dialysis Transplantation},\n\tauthor = {Del Águila García, María del Mar and Poyatos Andújar, Antonio M and Morales García, Ana Isabel and Martínez Atienza, Margarita and García Linares, Susana and Esteban de la Rosa, Rafael Jose},\n\tmonth = may,\n\tyear = {2021},\n\tkeywords = {Nephropathies, SOPHiA DDM},\n}\n\n

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\n Hereditary renal disease (HRD) is still underdiagnosed: although we know aspects related to autosomal dominant polycystic kidney disease (ADPKD), we know little about the incidence and prevalence of other entities such as Alport syndrome. Altogether, HRD can represent 15% of individuals undergoing renal replacement therapy (RRT) or could even be higher.The advancement of genetics at the healthcare level let to achieve accurate and early renal diagnoses, as well as the incorporation of genetic counseling to families, all of which will result in better management of the disease in its initial stages and the possibility of offering reproductive options that avoid transmission to offspring.Our objective is to know the performance offered by the implementation of the ERH panel through Next Generation Sequencing (NGS) in our healthcare area.Observational-descriptive study of 259 probands (141 men / 118 women), mean age of 46 years (30 pediatric / 123 over 50 years), with chronic kidney disease and suspected hereditary cause attended in the specialized consultation of our centers from October 2018 to October 2020. The DNA extracted from leukocytes obtained by venipuncture was processed with Nephropathies Solution version 3 panel (SOPHiA Genetics) according to the manufacturer's protocol. This panel covers the coding regions and splicing junctions of 44 HRD-related genes such as nephrotic syndromes, polycystic kidney diseases, Bartter syndromes, Alport syndrome, CAKUT or tubulopathies (table 1).MO046 Table 1:Genes included in the SOPHiA Genetics Nephropaties solution panel.The sequencing of the libraries was done in a MiSeq (Illumina Inc), the bioinformatic analysis of the data and annotation of variants was performed using the SOPHiA DDM 5.8.0.3 software, and the revision of variants by consulting the main databases (ClinVar, Exac, HGMD, NCBI, PKD Foundation, LOVD).The panel was informative (pathogenic or probably pathogenic) in 80/259 patients (31%) and 56/259 cases (21.66%) of variants of uncertain significance (VSI) were detected.Autosomal dominant polycystic kidney disease accounted for 76.2% of the variants identified (56.2% PKD1, 20% PKD2), following Alport syndrome with 15% and the alterations in the PKHD1 gene associated with renal polycystic disease in its recessive form with about 4% (Figure 1). We have also identified a case of autosomal dominant tubulointerstitial kidney disease associated with the UMOD gene that was not suspected until the genetic study was performed. We highlight that 45% (36/80) of the variants identified as responsible for the renal disease are not yet described. Overall, the most prevalent type of mutation is that which produces displacement in the reading frame or frameshift (Figure 2). Individually, frameshift is the most frequent alteration in PKD1, PKD2 and COL4A5, while for PKHD1, COL4A3 and COL4A4 it is missense.MO046 Figure 2: Types of mutations according to frequency.Our NGS HRD panel a) offers an adequate diagnostic performance at the healthcare level, with definitive results in 1 out of 3 cases and has also allowed the performance of many carrier studies among family members b) is able of diagnosing the most frequent disease, ADPKD and Alport syndrome, as well as unresolved or poorly characterized cases, and c) opens the horizon for new diagnoses, all without increasing costs by outsourcing services. All this makes the genetic study of renal pathology a useful and efficient strategy.These results encourage us to enhance the resources in this area that we consider to be of strategic value.\n

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\n \n\n \n \n \n \n \n Correlating qRT-PCR, dPCR and Viral Titration for the Identification and Quantification of SARS-CoV-2: A New Approach for Infection Management.\n \n \n \n\n\n \n Brandolini, M.; Taddei, F.; Marino, M. M.; Grumiro, L.; Scalcione, A.; Turba, M. E.; Gentilini, F.; Fantini, M.; Zannoli, S.; Dirani, G.; and Sambri, V.\n\n\n \n\n\n\n Viruses, 13(6). May 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{brandolini_correlating_2021,\n\ttitle = {Correlating {qRT}-{PCR}, {dPCR} and {Viral} {Titration} for the {Identification} and {Quantification} of {SARS}-{CoV}-2: {A} {New} {Approach} for {Infection} {Management}},\n\tvolume = {13},\n\tissn = {1999-4915},\n\tshorttitle = {Correlating {qRT}-{PCR}, {dPCR} and {Viral} {Titration} for the {Identification} and {Quantification} of {SARS}-{CoV}-2},\n\tdoi = {10.3390/v13061022},\n\tabstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in Wuhan, China, in late 2019 and is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) represents the gold standard for diagnostic assays even if it cannot precisely quantify viral RNA copies. Thus, we decided to compare qRT-PCR with digital polymerase chain reaction (dPCR), which is able to give an accurate number of RNA copies that can be found in a specimen. However, the aforementioned methods are not capable to discriminate if the detected RNA is infectious or not. For this purpose, it is necessary to perform an endpoint titration on cell cultures, which is largely used in the research field and provides a tissue culture infecting dose per mL (TCID50/mL) value. Both research and diagnostics call for a model that allows the comparison between the results obtained employing different analytical methods. The aim of this study is to define a comparison among two qRT-PCR protocols (one with preliminary RNA extraction and purification and an extraction-free qRT-PCR), a dPCR and a titration on cell cultures. The resulting correlations yield a faithful estimation of the total number of RNA copies and of the infectious viral burden from a Ct value obtained with diagnostic routine tests. All these estimations take into consideration methodological errors linked to the qRT-PCR, dPCR and titration assays.},\n\tlanguage = {eng},\n\tnumber = {6},\n\tjournal = {Viruses},\n\tauthor = {Brandolini, Martina and Taddei, Francesca and Marino, Maria Michela and Grumiro, Laura and Scalcione, Agata and Turba, Maria Elena and Gentilini, Fabio and Fantini, Michela and Zannoli, Silvia and Dirani, Giorgio and Sambri, Vittorio},\n\tmonth = may,\n\tyear = {2021},\n\tpmid = {34071726},\n\tkeywords = {Animals, COVID-19, Cells, Cultured, Chlorocebus aethiops, Ct, Digital Technology, Humans, Polymerase Chain Reaction, RNA copies, RNA, Viral, Reverse Transcriptase Polymerase Chain Reaction, SARS-CoV-2, SOPHiA DDM, TCID50/mL, Vero Cells, Viral Load, Virus Cultivation, dPCR, qRT-PCR, viral titration},\n}\n\n

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\n \n\n \n \n \n \n \n Mutational profile of ZBTB16-RARA-positive acute myeloid leukemia.\n \n \n \n\n\n \n Fabiani, E.; Cicconi, L.; Nardozza, A. M.; Cristiano, A.; Rossi, M.; Ottone, T.; Falconi, G.; Divona, M.; Testi, A. M.; Annibali, O.; Castelli, R.; Lazarevic, V.; Rego, E.; Montesinos, P.; Esteve, J.; Venditti, A.; Della Porta, M.; Arcese, W.; Lo-Coco, F.; and Voso, M. T.\n\n\n \n\n\n\n Cancer Medicine, 10(12): 3839–3847. June 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{fabiani_mutational_2021,\n\ttitle = {Mutational profile of {ZBTB16}-{RARA}-positive acute myeloid leukemia},\n\tvolume = {10},\n\tissn = {2045-7634},\n\tdoi = {10.1002/cam4.3904},\n\tabstract = {BACKGROUND: The ZBTB16-RARA fusion gene, resulting from the reciprocal translocation between ZBTB16 on chromosome 11 and RARA genes on chromosome 17 [t(11;17)(q23;q21)], is rarely observed in acute myeloid leukemia (AML), and accounts for about 1\\% of retinoic acid receptor-α (RARA) rearrangements. AML with this rare translocation shows unusual bone marrow (BM) morphology, with intermediate aspects between acute promyelocytic leukemia (APL) and AML with maturation. Patients may have a high incidence of disseminated intravascular coagulation at diagnosis, are poorly responsive to all-trans retinoic acid (ATRA) and arsenic tryoxyde, and are reported to have an overall poor prognosis.\nAIMS: The mutational profile of ZBTB16-RARA rearranged AML has not been described so far.\nMATERIALS AND METHODS: We performed targeted next-generation sequencing of 24 myeloid genes in BM diagnostic samples from seven ZBTB16-RARA+AML, 103 non-RARA rearranged AML, and 46 APL. The seven ZBTB16-RARA-positive patients were then screened for additional mutations using whole exome sequencing (n = 3) or an extended cancer panel including 409 genes (n = 4).\nRESULTS: ZBTB16-RARA+AML showed an intermediate number of mutations per patient and involvement of different genes, as compared to APL and other AMLs. In particular, we found a high incidence of ARID1A mutations in ZBTB16-RARA+AML (five of seven cases, 71\\%). Mutations in ARID2 and SMARCA4, other tumor suppressor genes also belonging to SWI/SNF chromatin remodeling complexes, were also identified in one case (14\\%).\nDISCUSSION AND CONCLUSION: Our data suggest the association of mutations of the ARID1A gene and of the other members of the SWI/SNF chromatin remodeling complexes with ZBTB16-RARA+AMLs, where they may support the peculiar disease phenotype.},\n\tlanguage = {eng},\n\tnumber = {12},\n\tjournal = {Cancer Medicine},\n\tauthor = {Fabiani, Emiliano and Cicconi, Laura and Nardozza, Anna Maria and Cristiano, Antonio and Rossi, Marianna and Ottone, Tiziana and Falconi, Giulia and Divona, Mariadomenica and Testi, Anna Maria and Annibali, Ombretta and Castelli, Roberto and Lazarevic, Vladimir and Rego, Eduardo and Montesinos, Pau and Esteve, Jordi and Venditti, Adriano and Della Porta, Matteo and Arcese, William and Lo-Coco, Francesco and Voso, Maria Teresa},\n\tmonth = jun,\n\tyear = {2021},\n\tpmid = {34042280},\n\tkeywords = {AML, ARID1A, MYS, Myeloid, NGS, ZBTB16-RARA},\n\tpages = {3839--3847},\n}\n\n

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\n \n\n \n \n \n \n \n Secondary findings in 622 Turkish clinical exome sequencing data.\n \n \n \n\n\n \n Arslan Ateş, E.; Türkyilmaz, A.; Yıldırım, Ö.; Alavanda, C.; Polat, H.; Demir, Ş.; Çebi, A. H.; Geçkinli, B. B.; Güney, A. İ.; Ata, P.; and Arman, A.\n\n\n \n\n\n\n Journal of Human Genetics. May 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{arslan_ates_secondary_2021,\n\ttitle = {Secondary findings in 622 {Turkish} clinical exome sequencing data},\n\tissn = {1435-232X},\n\tdoi = {10.1038/s10038-021-00936-8},\n\tabstract = {CES (Clinical Exome Sequencing) is a method that we use to diagnose rare diseases with nonspesific clinical features. Besides primary indication for testing genetic information may be detected about diseases which have not yet emerged. ACMG guidelines recommend to report pathogenic variations in medically actionable 59 genes. In this study we evaluated CES data of 622 cases which were tested for various indications. According to ACMG recommendations 59 genes were screened for reportable variations. The detected variations were reviewed using distinct databases and ACMG variation classification guidelines. Among 622 cases 13 (2.1\\%) had reportable variations including oncogenetic, cardiogenetic disorders, and malignant hyperthermia susceptibility-related genes. In 15 cases (2.4\\%) heterozygous pathogenic and likely pathogenic variations were detected in genes showing autosomal recessive inheritance. Ten novel variations causing truncated protein or splicing defect were reported. We detected 11 variations having conflicting interpretations in databases and 30 novel variations, predicted as likely pathogenic via insilico analysis tools which further evaluations are needed. As to our knowledge this is the first study investigating secondary findings in Turkish population. To extract the information that may lead to prevent severe morbidities and mortalities from big data is a valuable and lifesaving effort. Results of this study will contrbute to existing knowledge about secondary findings in exome sequencing and will be a pioneer for studies in Turkish population.},\n\tlanguage = {eng},\n\tjournal = {Journal of Human Genetics},\n\tauthor = {Arslan Ateş, Esra and Türkyilmaz, Ayberk and Yıldırım, Özlem and Alavanda, Ceren and Polat, Hamza and Demir, Şenol and Çebi, Alper Han and Geçkinli, Bilgen Bilge and Güney, Ahmet İlter and Ata, Pınar and Arman, Ahmet},\n\tmonth = may,\n\tyear = {2021},\n\tpmid = {34050257},\n\tkeywords = {CES v2},\n}\n\n

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\n \n\n \n \n \n \n \n \n Genetic profiling across multiple cancer types using molecular prescreening comprehensive gene panels offered by clinical trials (CT).\n \n \n \n \n\n\n \n Victoria, I.; Moreno Fernandez, D.; Angelats, L.; Indacochea, A.; Pelegrín, F.; Sole i Bentz, P.; Gaba, L.; Mellado, B.; Pineda, E.; Sauri, T.; Esposito, F.; Ferrer-Mileo, L.; Oliveres, H.; Muñoz, M.; Vidal, M.; Martinez Saez, O.; Basté Rotllán, N.; Vinolas, N.; Nogue, M.; and Garcia-Corbacho, J.\n\n\n \n\n\n\n Journal of Clinical Oncology, 39(15_suppl): 3060–3060. May 2021.\n Publisher: Wolters Kluwer\n\n\n\n
\n\n\n\n \n \n $\"Genetic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{victoria_genetic_2021,\n\ttitle = {Genetic profiling across multiple cancer types using molecular prescreening comprehensive gene panels offered by clinical trials ({CT}).},\n\tvolume = {39},\n\tissn = {0732-183X},\n\turl = {https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.3060},\n\tdoi = {10.1200/JCO.2021.39.15_suppl.3060},\n\tabstract = {3060Background: Genetic profiling (GP) is essential not only for understanding tumor biology but also helps to identify potential genes for targeted therapies. At the same time, selected CT provide an individual genomic profile panel during the pre-screening phase. Here, we demonstrate our experience using these panels. Methods: We selected 14 CT from our Early Drug Development Clinical Trial Unit at Hospital Clinic of Barcelona that included analysis of gene panels in tumor (Foundation One, ArcherDX, Therascreen and Sophia Genetics) or plasma (Resolution Bioscience ctDx). These panels analyzed mutations, fusions, amplifications, microsatellite instability (MSI) and tumor mutational burden (TMB), among others. We collected information about types of cancers, molecular alterations and therapies chosen according to the results of GP. The platform OncoKB (Chakravarty JCO PO, 2017) was used to define genes with potential target therapies and levels of evidence (LE) for those targets (from LE 1 –FDA-recognized biomarker predictive of response to an FDA-approved drug- to LE 4 –Compelling biological evidence supports the biomarker as being predictive of response to a drug). Descriptive statistics were used. Results: From March 2017 to January 2021 we analyzed samples from 410 patients (pts) with CNS (19.3\\%), urothelial (18.3\\%), prostate (17.6\\%), breast (15.4\\%), ovarian (9.3\\%), esophageal and gastric (5.4\\%), colorectal (4.4\\%), pancreas (2.7\\%), endometrial (2.4\\%), cholangiocarcinoma (1.2\\%), cervix (1\\%), HNSCC (1\\%), renal (1\\%), lung (0.5\\%), liver (0.2\\%) fallopian tube (0.2\\%) and paraganglioma (0.2\\%). 352 pts (85.8\\%) had at least 1 genetic alteration. The most frequently altered genes were TP53 (153 pts, 46.2\\%), INSR (19 pts, 22.8\\%), TERT (76 pts, 22\\%), CDKN2A (65 pts, 19.9\\%), FAM175A (11 pts, 19.3\\%), CDKN2B (54 pts, 18.1\\%), MLL2 (53 pts, 17.7\\%), PTEN (52 pts, 16\\%), MTAP (45 pts, 15.7\\%), PIK3CA (52 pts, 15\\%) and ATM (55 pts, 14.4\\%). TMB ranged from 0 to 76.9 mut/Mb (median 2.5 mut/Mb). MSI was found in 3 pts (1.5\\%). 196 pts (47.1\\%) had an OncoKB LE 1 alteration, 105 pts (25.6\\%) if we restrict the options to their specific cancer type. 16 pts (3.9\\%) received a matched therapy: 6 pts received an off-label drug, 6 pts were included in the same CT for which the pre-screening was performed and 4 pts were included in a different CT. Additionally, 13 pts (3.2\\%) received a matched therapy either with OncoKB LE 4 (5 pts received an off-label drug and 3 were included in a different CT) or not included in OncoKB (8 pts included in the same CT of the pre-screening). As a whole, 29 pts (7.1\\%) received a matched drug according to their genomic results. Conclusions: Comprehensive gene panel testing offered through CT allows the identification of targets to enroll pts, although the recruitment was 1.5\\%. However, 7.1\\% of the pts received a matched therapy due to the molecular information of these gene panels.},\n\tnumber = {15\\_suppl},\n\turldate = {2021-06-18},\n\tjournal = {Journal of Clinical Oncology},\n\tauthor = {Victoria, Iván and Moreno Fernandez, Debora and Angelats, Laura and Indacochea, Alberto and Pelegrín, Francisco and Sole i Bentz, Pol and Gaba, Lydia and Mellado, Begona and Pineda, Estela and Sauri, Tamara and Esposito, Francis and Ferrer-Mileo, Laura and Oliveres, Helena and Muñoz, Montserrat and Vidal, Maria and Martinez Saez, Olga and Basté Rotllán, Neus and Vinolas, Nuria and Nogue, Miquel and Garcia-Corbacho, Javier},\n\tmonth = may,\n\tyear = {2021},\n\tnote = {Publisher: Wolters Kluwer},\n\tpages = {3060--3060},\n}\n\n

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\n 3060Background: Genetic profiling (GP) is essential not only for understanding tumor biology but also helps to identify potential genes for targeted therapies. At the same time, selected CT provide an individual genomic profile panel during the pre-screening phase. Here, we demonstrate our experience using these panels. Methods: We selected 14 CT from our Early Drug Development Clinical Trial Unit at Hospital Clinic of Barcelona that included analysis of gene panels in tumor (Foundation One, ArcherDX, Therascreen and Sophia Genetics) or plasma (Resolution Bioscience ctDx). These panels analyzed mutations, fusions, amplifications, microsatellite instability (MSI) and tumor mutational burden (TMB), among others. We collected information about types of cancers, molecular alterations and therapies chosen according to the results of GP. The platform OncoKB (Chakravarty JCO PO, 2017) was used to define genes with potential target therapies and levels of evidence (LE) for those targets (from LE 1 –FDA-recognized biomarker predictive of response to an FDA-approved drug- to LE 4 –Compelling biological evidence supports the biomarker as being predictive of response to a drug). Descriptive statistics were used. Results: From March 2017 to January 2021 we analyzed samples from 410 patients (pts) with CNS (19.3%), urothelial (18.3%), prostate (17.6%), breast (15.4%), ovarian (9.3%), esophageal and gastric (5.4%), colorectal (4.4%), pancreas (2.7%), endometrial (2.4%), cholangiocarcinoma (1.2%), cervix (1%), HNSCC (1%), renal (1%), lung (0.5%), liver (0.2%) fallopian tube (0.2%) and paraganglioma (0.2%). 352 pts (85.8%) had at least 1 genetic alteration. The most frequently altered genes were TP53 (153 pts, 46.2%), INSR (19 pts, 22.8%), TERT (76 pts, 22%), CDKN2A (65 pts, 19.9%), FAM175A (11 pts, 19.3%), CDKN2B (54 pts, 18.1%), MLL2 (53 pts, 17.7%), PTEN (52 pts, 16%), MTAP (45 pts, 15.7%), PIK3CA (52 pts, 15%) and ATM (55 pts, 14.4%). TMB ranged from 0 to 76.9 mut/Mb (median 2.5 mut/Mb). MSI was found in 3 pts (1.5%). 196 pts (47.1%) had an OncoKB LE 1 alteration, 105 pts (25.6%) if we restrict the options to their specific cancer type. 16 pts (3.9%) received a matched therapy: 6 pts received an off-label drug, 6 pts were included in the same CT for which the pre-screening was performed and 4 pts were included in a different CT. Additionally, 13 pts (3.2%) received a matched therapy either with OncoKB LE 4 (5 pts received an off-label drug and 3 were included in a different CT) or not included in OncoKB (8 pts included in the same CT of the pre-screening). As a whole, 29 pts (7.1%) received a matched drug according to their genomic results. Conclusions: Comprehensive gene panel testing offered through CT allows the identification of targets to enroll pts, although the recruitment was 1.5%. However, 7.1% of the pts received a matched therapy due to the molecular information of these gene panels.\n

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\n \n\n \n \n \n \n \n \n Germline mutations in MSH2 and ATM gene in patients with GIST (gastrointestinal stromal tumor) and second epitelial tumors.\n \n \n \n \n\n\n \n Gasperoni, S.; Papi, L.; Castiglione, F.; Gensini, F.; Sestini, R.; Messerini, L.; Bartoli, C.; Nozzoli, F.; Dimarino, M.; Cianchi, F.; Taddei, A.; Ferrara, A.; Calistri, M.; Bencini, L.; Perna, F.; Catalano, M.; Giorgione, R.; Winchler, C.; Venturi, G.; and Mini, E.\n\n\n \n\n\n\n Journal of Clinical Oncology, 39(15_suppl): e23520–e23520. May 2021.\n Publisher: Wolters Kluwer\n\n\n\n
\n\n\n\n \n \n $\"Germline$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{gasperoni_germline_2021,\n\ttitle = {Germline mutations in {MSH2} and {ATM} gene in patients with {GIST} (gastrointestinal stromal tumor) and second epitelial tumors.},\n\tvolume = {39},\n\tissn = {0732-183X},\n\turl = {https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.e23520},\n\tdoi = {10.1200/JCO.2021.39.15_suppl.e23520},\n\tabstract = {e23520Background: In adult GISTs are frequently sporadic, while rarely GISTs are linked to Carney Triad and Carney-Stratakis Syndrome and NF1. GISTs with second primary tumors are reported in 4-33\\% of patients in literature and genetic counseling is suggested to explore an underlying germline mutations pathway. Methods: In our Academic Hospital Centre (EURACAN member) in Florence, Italy, we are following patients with GIST and multiple primary tumors with genetic counseling (72 GISTs with second tumors/185 patients with GIST) and germline analysis of the following genetic panel is performed as clinically indicated: BRCA1, BRCA2, MUTYH, MLH1, MSH2, MSH6, CDH1, ATM, TP53, PTEN, CHECK2, PALB2, BARD1, BRIP1, BLM, RAD51C, RAD51D, XRCC2, PMS2, MRE11A, RAD50, NBN, FAM175A, EPKAM, TSK1, MEN1 by sequencing analysis with Illumina MiSeq by kit multiplicom BRCA Hereditary cancer Mastr plus, and bioinformatic analysis by software SOPHIADDM (Sophia genetics) for point genetic alterations of BRCA1 NM\\_007294.3, BRCA2 NM\\_000059.3, MUTYH NM\\_000249, MSH2 NM\\_000251, MSH6 NM\\_000179, CDH1 NM\\_00444360, ATM NM\\_000051, TP53 NM\\_000546, PTEN NM\\_000314, CHEK2 NM\\_001005735, PALB2 NM\\_024675, BARD1 NM\\_000465, BRIP1 NM\\_032043, BLM NM\\_000057, RAD51C NM\\_002876, RAD51D NM\\_001142571, XRCC2 NM\\_005431, PMS2 NM\\_000535, MRE11A NM\\_005590, RAD50 NM\\_006732, NBN NM\\_002485, FAM175A NM\\_139076, EPCAM NM\\_002354, STK1 NM\\_000455, MEN1 NM\\_000244 and MLPA (Multiplex Ligation-dependent Probe Amplification) test analysis for patients with kit P087-BRCA1,P045-BRCA2(CHEK2, P248-MLH1-MSH2, P003-MLH1/MSH2, P072-MSH6-MUTYH (MRC-Holland). Results: In 3 patients germline mutations have been observed: 1 patient showed the c.1192dupG, p.(Ala398Glyfs*19) pathogenic mutation in exon 7 of MSH2 gene, confirmed by Sanger Sequencing, 1 patient showed c.565-?\\_1130+?del mutation consisting in heterozygous 3-4-5-6 exons deletion of MSH2 gene, confirmed by MLPA analysis, and in 1 patient the following ATM alteration has been identified in heterozygosis: ATM c.5319+2T {\\textgreater} C, p.(?). In the 2 patients with Lynch syndrome with colon adenocarcinoma (MSI-H), synchronous GISTs (1 patient quadruple WT and 1 patient kit ex 11 mutated ) were diagnosed; in the patient with ATM mutation, the diagnosis of GIST (kit ex 11 mutated) occurred after prostate adenocarcinoma and before colon adenocarcinoma (MSI-H). Conclusions: Our analysis suggests that GIST diagnosis could be tumor-related to multiple hereditary tumor syndromes as Lynch Syndrome and Ataxia-Teleangectasia syndrome, the latter being linked in eterozygosis to tumor susceptibility to breast in female. This report represents a high value in terms of genetic counseling for relatives and in terms of therapeutic implications for the patients.},\n\tnumber = {15\\_suppl},\n\turldate = {2021-06-18},\n\tjournal = {Journal of Clinical Oncology},\n\tauthor = {Gasperoni, Silvia and Papi, Laura and Castiglione, Francesca and Gensini, Francesca and Sestini, Roberta and Messerini, Luca and Bartoli, Caterina and Nozzoli, Filippo and Dimarino, Michele and Cianchi, Fabio and Taddei, Antonio and Ferrara, Angelo and Calistri, Massimo and Bencini, Lapo and Perna, Federico and Catalano, Martina and Giorgione, Roberta and Winchler, Costanza and Venturi, Giulia and Mini, Enrico},\n\tmonth = may,\n\tyear = {2021},\n\tnote = {Publisher: Wolters Kluwer},\n\tkeywords = {ATM, Germline, MSH2, SOPHiA DDM},\n\tpages = {e23520--e23520},\n}\n\n

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\n e23520Background: In adult GISTs are frequently sporadic, while rarely GISTs are linked to Carney Triad and Carney-Stratakis Syndrome and NF1. GISTs with second primary tumors are reported in 4-33% of patients in literature and genetic counseling is suggested to explore an underlying germline mutations pathway. Methods: In our Academic Hospital Centre (EURACAN member) in Florence, Italy, we are following patients with GIST and multiple primary tumors with genetic counseling (72 GISTs with second tumors/185 patients with GIST) and germline analysis of the following genetic panel is performed as clinically indicated: BRCA1, BRCA2, MUTYH, MLH1, MSH2, MSH6, CDH1, ATM, TP53, PTEN, CHECK2, PALB2, BARD1, BRIP1, BLM, RAD51C, RAD51D, XRCC2, PMS2, MRE11A, RAD50, NBN, FAM175A, EPKAM, TSK1, MEN1 by sequencing analysis with Illumina MiSeq by kit multiplicom BRCA Hereditary cancer Mastr plus, and bioinformatic analysis by software SOPHIADDM (Sophia genetics) for point genetic alterations of BRCA1 NM_007294.3, BRCA2 NM_000059.3, MUTYH NM_000249, MSH2 NM_000251, MSH6 NM_000179, CDH1 NM_00444360, ATM NM_000051, TP53 NM_000546, PTEN NM_000314, CHEK2 NM_001005735, PALB2 NM_024675, BARD1 NM_000465, BRIP1 NM_032043, BLM NM_000057, RAD51C NM_002876, RAD51D NM_001142571, XRCC2 NM_005431, PMS2 NM_000535, MRE11A NM_005590, RAD50 NM_006732, NBN NM_002485, FAM175A NM_139076, EPCAM NM_002354, STK1 NM_000455, MEN1 NM_000244 and MLPA (Multiplex Ligation-dependent Probe Amplification) test analysis for patients with kit P087-BRCA1,P045-BRCA2(CHEK2, P248-MLH1-MSH2, P003-MLH1/MSH2, P072-MSH6-MUTYH (MRC-Holland). Results: In 3 patients germline mutations have been observed: 1 patient showed the c.1192dupG, p.(Ala398Glyfs*19) pathogenic mutation in exon 7 of MSH2 gene, confirmed by Sanger Sequencing, 1 patient showed c.565-?_1130+?del mutation consisting in heterozygous 3-4-5-6 exons deletion of MSH2 gene, confirmed by MLPA analysis, and in 1 patient the following ATM alteration has been identified in heterozygosis: ATM c.5319+2T \\textgreater C, p.(?). In the 2 patients with Lynch syndrome with colon adenocarcinoma (MSI-H), synchronous GISTs (1 patient quadruple WT and 1 patient kit ex 11 mutated ) were diagnosed; in the patient with ATM mutation, the diagnosis of GIST (kit ex 11 mutated) occurred after prostate adenocarcinoma and before colon adenocarcinoma (MSI-H). Conclusions: Our analysis suggests that GIST diagnosis could be tumor-related to multiple hereditary tumor syndromes as Lynch Syndrome and Ataxia-Teleangectasia syndrome, the latter being linked in eterozygosis to tumor susceptibility to breast in female. This report represents a high value in terms of genetic counseling for relatives and in terms of therapeutic implications for the patients.\n

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\n \n\n \n \n \n \n \n Expanding the clinical spectrum in trichohepatoenteric syndrome.\n \n \n \n\n\n \n Dorum, S.; and Gorukmez, O.\n\n\n \n\n\n\n American Journal of Medical Genetics. Part A. May 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{dorum_expanding_2021,\n\ttitle = {Expanding the clinical spectrum in trichohepatoenteric syndrome},\n\tissn = {1552-4833},\n\tdoi = {10.1002/ajmg.a.62354},\n\tabstract = {Trichohepatoenteric syndrome (THES) is a very rare autosomal recessive genetic disorder, which is characterized by intractable diarrhea during infancy, dysmorphic features, immunodeficiency, and a failure to thrive. There are still significant difficulties for patients and clinicians in terms of the management of THES, even though its molecular basis has been uncovered in the last decade. In this article, we have presented two cases relating to siblings that have been diagnosed with the condition. Concerning one of the patients, we described a novel variation (c.2114 + 5G {\\textgreater} A) in the TTC37 gene and a mild clinical course; meanwhile, the other one was clinically diagnosed with THES at 17 years of age, but they had seizures and died suddenly. These cases expand the spectrum of clinical findings in relation to THES.},\n\tlanguage = {eng},\n\tjournal = {American Journal of Medical Genetics. Part A},\n\tauthor = {Dorum, Sevil and Gorukmez, Ozlem},\n\tmonth = may,\n\tyear = {2021},\n\tpmid = {34037310},\n\tkeywords = {CES, TTC37 gene, intractable diarrhea, trichohepatoenteric syndrome},\n}\n\n

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\n \n\n \n \n \n \n \n Comprehensive analysis of DNA damage repair genes reveals pathogenic variants beyond BRCA and suggests the need for extensive genetic testing in pancreatic cancer.\n \n \n \n\n\n \n Rapposelli, I. G.; Zampiga, V.; Cangini, I.; Arcangeli, V.; Ravegnani, M.; Valgiusti, M.; Pini, S.; Tamberi, S.; Bartolini, G.; Passardi, A.; Martinelli, G.; Calistri, D.; Frassineti, G. L.; Falcini, F.; and Danesi, R.\n\n\n \n\n\n\n BMC cancer, 21(1): 611. May 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{rapposelli_comprehensive_2021,\n\ttitle = {Comprehensive analysis of {DNA} damage repair genes reveals pathogenic variants beyond {BRCA} and suggests the need for extensive genetic testing in pancreatic cancer},\n\tvolume = {21},\n\tissn = {1471-2407},\n\tdoi = {10.1186/s12885-021-08368-5},\n\tabstract = {BACKGROUND: Pancreatic cancer (PC) is a major cause of cancer death. In an effort to improve treatment strategies and outcomes, DNA damage repair (DDR) pathways have been introduced as a new target in PC and in other cancers, through the exploitation of synthetic lethality. Furthermore, genes involved in DDR are among the major determinants of cancer susceptibility. In addition to the well-known BRCA1 and BRCA2 genes, a plethora of other targets in the same pathways are now emerging.\nMETHODS: We analyzed samples from 60 patients, affected by PC and already tested for BRCA, using a panel with 24 other cancer susceptibility genes.\nRESULTS: We detected 8 pathogenic or likely pathogenic mutations (13.3\\% of samples analyzed), 4 of which were found in non-BRCA genes (2 in ATM, 1 each in PALB2 and RAD50). Furthermore, 4 pathogenic or likely pathogenic mutations were found in patients without a personal or familial history of cancer.\nCONCLUSIONS: Our results suggest that genetic testing with a comprehensive gene panel should be perfomed in all patients with PC, in order to allow screening for PC and other gene-related cancers in all at risk family members and to assess patients' eligibility for emerging therapeutic options.},\n\tlanguage = {eng},\n\tnumber = {1},\n\tjournal = {BMC cancer},\n\tauthor = {Rapposelli, Ilario Giovanni and Zampiga, Valentina and Cangini, Ilaria and Arcangeli, Valentina and Ravegnani, Mila and Valgiusti, Martina and Pini, Sara and Tamberi, Stefano and Bartolini, Giulia and Passardi, Alessandro and Martinelli, Giovanni and Calistri, Daniele and Frassineti, Giovanni Luca and Falcini, Fabio and Danesi, Rita},\n\tmonth = may,\n\tyear = {2021},\n\tpmid = {34034685},\n\tpmcid = {PMC8152298},\n\tkeywords = {Cancer susceptibility, DNA damage repair, Gene panel, HCS, Pancreatic cancer, Targeted therapy},\n\tpages = {611},\n}\n\n

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\n \n\n \n \n \n \n \n Recently defined epileptic encephalopathy related to WWOX gene mutation: six patients and new mutations.\n \n \n \n\n\n \n Havali, C.; Ekici, A.; Dorum, S.; Görükmez, Ö.; and Topak, A.\n\n\n \n\n\n\n Neurological Research,1–7. May 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{havali_recently_2021,\n\ttitle = {Recently defined epileptic encephalopathy related to {WWOX} gene mutation: six patients and new mutations},\n\tissn = {1743-1328},\n\tshorttitle = {Recently defined epileptic encephalopathy related to {WWOX} gene mutation},\n\tdoi = {10.1080/01616412.2021.1932173},\n\tabstract = {Purpose: Pathogenic variants of the WWOX gene have been linked to sexual differentiation disorders, spinocerebellar ataxia, and epileptic encephalopathy (EE). We evaluated the clinical and molecular data from six newly diagnosed patients with WWOX-related EE.Methods: Clinical and molecular findings in six patients with EE were investigated, and biallelic pathogenic variants in the WWOX gene were identified. Clinical exome sequencing and Sanger sequencing were performed.Results: Three variations, as well as two novel mutations, in the WWOX gene were detected.Conclusion: Pathogenic WWOX mutations are associated with early-onset EE. Here, we report the case of six children with WWOX-related EE.},\n\tlanguage = {eng},\n\tjournal = {Neurological Research},\n\tauthor = {Havali, Cengiz and Ekici, Arzu and Dorum, Sevil and Görükmez, Özlem and Topak, Ali},\n\tmonth = may,\n\tyear = {2021},\n\tpmid = {34034642},\n\tkeywords = {CES, WOREE syndrome, WWOX, epileptic encephalopathy, infant},\n\tpages = {1--7},\n}\n\n

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\n \n\n \n \n \n \n \n A Large Family with p.Arg554His Mutation in ABCD1: Clinical Features and Genotype/Phenotype Correlation in Female Carriers.\n \n \n \n\n\n \n Campopiano, R.; Femiano, C.; Chiaravalloti, M. A.; Ferese, R.; Centonze, D.; Buttari, F.; Zampatti, S.; Fanelli, M.; Amatori, S.; D'Alessio, C.; Giardina, E.; Fornai, F.; Biagioni, F.; Storto, M.; and Gambardella, S.\n\n\n \n\n\n\n Genes, 12(5). May 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{campopiano_large_2021,\n\ttitle = {A {Large} {Family} with p.{Arg554His} {Mutation} in {ABCD1}: {Clinical} {Features} and {Genotype}/{Phenotype} {Correlation} in {Female} {Carriers}},\n\tvolume = {12},\n\tissn = {2073-4425},\n\tshorttitle = {A {Large} {Family} with p.{Arg554His} {Mutation} in {ABCD1}},\n\tdoi = {10.3390/genes12050775},\n\tabstract = {X-linked adrenoleukodystrophy (X-ALD, OMIM \\#300100) is the most common peroxisomal disorder clinically characterized by two main phenotypes: adrenomyeloneuropathy (AMN) and the cerebral demyelinating form of X-ALD (cerebral ALD). The disease is caused by defects in the gene for the adenosine triphosphate (ATP)-binding cassette protein, subfamily D (ABCD1) that encodes the peroxisomal transporter of very-long-chain fatty acids (VLCFAs). The defective function of ABCD1 protein prevents β-oxidation of VLCFAs, which thus accumulate in tissues and plasma, to represent the hallmark of the disease. As in many X-linked diseases, it has been routinely expected that female carriers are asymptomatic. Nonetheless, recent findings indicate that most ABCD1 female carriers become symptomatic, with a motor disability that typically appears between the fourth and fifth decade. In this paper, we report a large family in which affected males died during the first decade, while affected females develop, during the fourth decade, progressive lower limb weakness with spastic or ataxic-spastic gait, tetra-hyperreflexia with sensory alterations. Clinical and genetic evaluations were performed in nine subjects, eight females (five affected and three healthy) and one healthy male. All affected females were carriers of the c.1661G{\\textgreater}A (p.Arg554His, rs201568579) mutation. This study strengthens the relevance of clinical symptoms in female carriers of ABCD1 mutations, which leads to a better understanding of the role of the genetic background and the genotype-phenotype correlation. This indicates the relevance to include ABCD1 genes in genetic panels for gait disturbance in women.},\n\tlanguage = {eng},\n\tnumber = {5},\n\tjournal = {Genes},\n\tauthor = {Campopiano, Rosa and Femiano, Cinzia and Chiaravalloti, Maria Antonietta and Ferese, Rosangela and Centonze, Diego and Buttari, Fabio and Zampatti, Stefania and Fanelli, Mirco and Amatori, Stefano and D'Alessio, Carmelo and Giardina, Emiliano and Fornai, Francesco and Biagioni, Francesca and Storto, Marianna and Gambardella, Stefano},\n\tmonth = may,\n\tyear = {2021},\n\tpmid = {34069712},\n\tpmcid = {PMC8160645},\n\tkeywords = {ABCD1, CES, SOPHiA DDM, X-linked adrenoleukodystrophy, diagnosis, neurogenetics, next generation sequencing},\n}\n\n

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\n \n\n \n \n \n \n \n Phenotype-driven variant filtration strategy in exome sequencing toward a high diagnostic yield and identification of 85 novel variants in 400 patients with rare Mendelian disorders.\n \n \n \n\n\n \n Marinakis, N. M.; Svingou, M.; Veltra, D.; Kekou, K.; Sofocleous, C.; Tilemis, F.; Kosma, K.; Tsoutsou, E.; Fryssira, H.; and Traeger-Synodinos, J.\n\n\n \n\n\n\n American Journal of Medical Genetics. Part A. May 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{marinakis_phenotype-driven_2021,\n\ttitle = {Phenotype-driven variant filtration strategy in exome sequencing toward a high diagnostic yield and identification of 85 novel variants in 400 patients with rare {Mendelian} disorders},\n\tissn = {1552-4833},\n\tdoi = {10.1002/ajmg.a.62338},\n\tabstract = {About 6000 to 7000 different rare disorders with suspected genetic etiologies have been described and almost 4500 causative gene(s) have been identified. The advent of next-generation sequencing (NGS) technologies has revolutionized genomic research and diagnostics, representing a major advance in the identification of pathogenic genetic variations. This study presents a 3-year experience from an academic genetics center, where 400 patients were referred for genetic analysis of disorders with unknown etiology. A phenotype-driven proband-only exome sequencing (ES) strategy was applied for the investigation of rare disorders, in the context of optimizing ES diagnostic yield and minimizing costs and time to definitive diagnosis. Overall molecular diagnostic yield reached 53\\% and characterized 243 pathogenic variants in 210 cases, 85 of which were novel and 148 known, contributing information to the community of disease and variant databases. ES provides an opportunity to resolve the genetic etiology of disorders and support appropriate medical management and genetic counseling. In cases with complex phenotypes, the identification of complex genotypes may contribute to more comprehensive clinical management. In the context of effective multidisciplinary collaboration between clinicians and laboratories, ES provides an efficient and appropriate tool for first-tier genomic analysis.},\n\tlanguage = {eng},\n\tjournal = {American Journal of Medical Genetics. Part A},\n\tauthor = {Marinakis, Nikolaos M. and Svingou, Maria and Veltra, Danai and Kekou, Kyriaki and Sofocleous, Christalena and Tilemis, Faidon-Nikolaos and Kosma, Konstantina and Tsoutsou, Eirini and Fryssira, Helen and Traeger-Synodinos, Joanne},\n\tmonth = may,\n\tyear = {2021},\n\tpmid = {34008892},\n\tkeywords = {CES, Mendelian disorders, WES, complex genotype, diagnostic yield, exome sequencing, phenotype-driven strategy},\n}\n\n

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\n \n\n \n \n \n \n \n \n Evaluation of the Idylla ctEGFR mutation assay to detect EGFR mutations in plasma from patients with non-small cell lung cancers.\n \n \n \n \n\n\n \n Gilson, P.; Saurel, C.; Salleron, J.; Husson, M.; Demange, J.; Merlin, J.; and Harlé, A.\n\n\n \n\n\n\n Scientific Reports, 11(1): 10470. May 2021.\n Bandiera_abtest: a Cc_license_type: cc_by Cg_type: Nature Research Journals Number: 1 Primary_atype: Research Publisher: Nature Publishing Group Subject_term: Cancer genomics;Non-small-cell lung cancer Subject_term_id: cancer-genomics;non-small-cell-lung-cancer\n\n\n\n
\n\n\n\n \n \n $\"Evaluation$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{gilson_evaluation_2021,\n\ttitle = {Evaluation of the {Idylla} {ctEGFR} mutation assay to detect {EGFR} mutations in plasma from patients with non-small cell lung cancers},\n\tvolume = {11},\n\tcopyright = {2021 The Author(s)},\n\tissn = {2045-2322},\n\turl = {https://www.nature.com/articles/s41598-021-90091-z},\n\tdoi = {10.1038/s41598-021-90091-z},\n\tabstract = {The assessment of EGFR mutations is recommended for the management of patients with non-small cell lung cancer (NSCLC). Presence of EGFR mutation is associated with response or resistance to EGFR tyrosine kinase inhibitors (EGFR-TKI). Liquid biopsy is nowadays widely used for the detection of resistance to EGFR-TKI. We evaluated here the performance of the Idylla ctEGFR mutation assay for the detection of EGFR mutations in circulating tumour DNA (ctDNA) in plasma from patients with NSCLC. Previously characterized plasma samples from 38 patients with NSCLC were analysed using 2 different analytical conditions (C1 and C2). The limit of detection (LOD) was evaluated using 2 mL of healthy donor plasma spiked with commercial DNA controls. Overall agreement, sensitivity and specificity were 92.1\\%, 86.7\\% and 95.7\\% for C1 condition respectively and 94.7\\%, 86.7\\% and 100\\% for C2 condition respectively. The T790M secondary resistance mutation was detected in two samples out of 3. The Idylla system was able to detect the exon 19 deletion from 6 copies/mL and up to 91 copies/mL for the G719S mutation. These results support that the Idylla ctEGFR mutation assay is a rapid option for the detection of EGFR hotspots mutations in plasma samples, however a particular attention is needed for its interpretation.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2021-06-18},\n\tjournal = {Scientific Reports},\n\tauthor = {Gilson, Pauline and Saurel, Chloé and Salleron, Julia and Husson, Marie and Demange, Jessica and Merlin, Jean-Louis and Harlé, Alexandre},\n\tmonth = may,\n\tyear = {2021},\n\tnote = {Bandiera\\_abtest: a\nCc\\_license\\_type: cc\\_by\nCg\\_type: Nature Research Journals\nNumber: 1\nPrimary\\_atype: Research\nPublisher: Nature Publishing Group\nSubject\\_term: Cancer genomics;Non-small-cell lung cancer\nSubject\\_term\\_id: cancer-genomics;non-small-cell-lung-cancer},\n\tkeywords = {EGFR, Lung Cancer, SOPHiA DDM, STS},\n\tpages = {10470},\n}\n\n

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\n \n\n \n \n \n \n \n \n Dysgenesis and dysfunction of pancreas and pituitary due to FOXA2 gene defects.\n \n \n \n \n\n\n \n Kaygusuz, S. B.; Arslan Ates, E.; Vignola, M. L.; Volkan, B.; Geckinli, B. B.; Turan, S.; Bereket, A.; Gaston-Massuet, C.; and Guran, T.\n\n\n \n\n\n\n The Journal of Clinical Endocrinology & Metabolism, (dgab352). May 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Dysgenesis$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{kaygusuz_dysgenesis_2021,\n\ttitle = {Dysgenesis and dysfunction of pancreas and pituitary due to {FOXA2} gene defects},\n\tissn = {0021-972X},\n\turl = {https://doi.org/10.1210/clinem/dgab352},\n\tdoi = {10.1210/clinem/dgab352},\n\tabstract = {Developmental disorders of the pituitary gland leading to congenital hypopituitarism can either be isolated or associated with extra-pituitary abnormalities (syndromic hypopituitarism). A large number of syndromic hypopituitarism cases are linked to mutations in transcription factors. The Forkhead box A2 (FOXA2) is a transcription factor that plays a key role in the central nervous system, foregut and pancreatic development.To characterize two patients with syndromic hypopituitarism due to FOXA2 gene defects.We report a novel heterozygous nonsense c.616C\\&gt;T (p.Q206X) variant, which leads to a truncated protein that lacks part of the DNA-binding domain of FOXA2, resulting in impaired transcriptional activation of the GLUT2-luciferase reporter. The patient is the sixth patient described in the literature with a FOXA2 mutation, and the first patient exhibiting pancreatic hypoplasia. We also report a second patient with a novel de novo 8.53 megabase (Mb) deletion of 20p11.2 that encompasses FOXA2, who developed diabetes mellitus that responded to sulfonylurea treatment.Our two cases broaden the molecular and clinical spectrum of FOXA2-related disease, reporting the first nonsense mutation and the first case of pancreatic dysgenesis.},\n\tnumber = {dgab352},\n\turldate = {2021-06-18},\n\tjournal = {The Journal of Clinical Endocrinology \\& Metabolism},\n\tauthor = {Kaygusuz, Sare Betul and Arslan Ates, Esra and Vignola, Maria Lillina and Volkan, Burcu and Geckinli, Bilgen Bilge and Turan, Serap and Bereket, Abdullah and Gaston-Massuet, Carles and Guran, Tulay},\n\tmonth = may,\n\tyear = {2021},\n\tkeywords = {CES v2, Pancreatitis, SOPHiA DDM},\n}\n\n

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\n \n\n \n \n \n \n \n Mutation spectrum of hereditary myopathies in Turkish patients and novel variants.\n \n \n \n\n\n \n Saat, H.; and Sahin, I.\n\n\n \n\n\n\n Annals of Human Genetics. May 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{saat_mutation_2021,\n\ttitle = {Mutation spectrum of hereditary myopathies in {Turkish} patients and novel variants},\n\tissn = {1469-1809},\n\tdoi = {10.1111/ahg.12429},\n\tabstract = {Hereditary myopathies are a heterogeneous disorder known to be associated with more than 100 genes. Although hereditary myopathy subgroups can be partially described with traditional methods such as muscle biopsy, next-generation sequencing (NGS) is essential to reveal the disease's underlying genetic etiology and molecular mechanisms. In this study, we performed clinical exome sequencing or whole-exome sequencing (CES/WES) in 20 unrelated Turkish patients. Thirteen pathogenic or likely pathogenic variants, including five novel variantswere detected in the 16 known hereditary myopathy genes. We achieved a high rate of diagnosis (65\\%) compared to previous studies. The most common condition noticed was limb-girdle muscular dystrophy (LGMD), which should not be ignored in patients diagnosed with myopathy. CES or WES provides a certain molecular diagnosis from a broad perspective to demonstrate underlying genetic causes in heterogeneous disorders. Therefore, exome sequencing offers a higher and more complete diagnosis than the gene panel.},\n\tlanguage = {eng},\n\tjournal = {Annals of Human Genetics},\n\tauthor = {Saat, Hanife and Sahin, Ibrahim},\n\tmonth = may,\n\tyear = {2021},\n\tpmid = {33963534},\n\tkeywords = {CES, WES, congenital myopathies, hereditary myopathies, muscular dystrophies, next-generation sequencing (NGS)},\n}\n\n

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\n \n\n \n \n \n \n \n \n 34P New pathogenic germline mutation in ATM gene in Khakass breast cancer patients.\n \n \n \n \n\n\n \n Gervas, P.; and Cherdyntseva, N.\n\n\n \n\n\n\n Annals of Oncology, 32: S34. May 2021.\n Publisher: Elsevier\n\n\n\n
\n\n\n\n \n \n $\"34P$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{gervas_34p_2021,\n\ttitle = {{34P} {New} pathogenic germline mutation in {ATM} gene in {Khakass} breast cancer patients},\n\tvolume = {32},\n\tissn = {0923-7534, 1569-8041},\n\turl = {https://www.annalsofoncology.org/article/S0923-7534(21)00926-1/abstract},\n\tdoi = {10.1016/j.annonc.2021.03.048},\n\tabstract = {In Russia, more than 50,000 women are diagnosed with breast cancer every year. Russia\nis a multinational country - about 200 ethnic groups live on its territory. To date,\nthere are a limited number of reports on inherited gene mutations associated with\nbreast cancer among Khakass (Mongoloid indigenous people in Russia). The aim of this\nstudy was to assess the prevalence of mutations of breast cancer-associated genes\nin 27 Khakass women with breast cancer.},\n\tlanguage = {English},\n\turldate = {2021-05-20},\n\tjournal = {Annals of Oncology},\n\tauthor = {Gervas, P. and Cherdyntseva, N.},\n\tmonth = may,\n\tyear = {2021},\n\tnote = {Publisher: Elsevier},\n\tkeywords = {HCS},\n\tpages = {S34},\n}\n\n

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\n \n\n \n \n \n \n \n \n Clinical characteristics and molecular genetic analysis of a cohort with idiopathic congenital hypogonadism.\n \n \n \n \n\n\n \n Turkyilmaz, A.; Cayir, A.; Yarali, O.; Kurnaz, E.; Baykan, E. K.; Ates, E. A.; and Demirbilek, H.\n\n\n \n\n\n\n Journal of Pediatric Endocrinology and Metabolism. April 2021.\n Publisher: De Gruyter Section: Journal of Pediatric Endocrinology and Metabolism\n\n\n\n
\n\n\n\n \n \n $\"Clinical$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{turkyilmaz_clinical_2021,\n\ttitle = {Clinical characteristics and molecular genetic analysis of a cohort with idiopathic congenital hypogonadism},\n\tissn = {2191-0251},\n\turl = {https://www.degruyter.com/document/doi/10.1515/jpem-2020-0590/html},\n\tdoi = {10.1515/jpem-2020-0590},\n\tabstract = {Objectives Hypogonadism is defined as inadequate sex hormone production due to defects in the hypothalamic-pituitary-gonadal axis. In recent years, rare single gene defects have been identified in both hypergonadotropic hypogonadism (Hh), and hypogonadotropic hypogonadism (HH) cases with no chromosomal anomalies. The aim of the present study is to investigate the underlying molecular genetic etiology and the genotype-phenotype relationship of a series of patients with Hh and HH. Methods In total, 27 HH and six Hh cases were evaluated. Clinical and laboratory features are extracted from patients’ hospital files. Whole exome sequencing (WES) analysis was performed. Results A total of 27 HH cases (15 female) (mean age: 15.8 ± 2.7 years) and six Hh patients (six females) (mean age: 14.9 ± 1.2 years) were included. In molecular genetic analysis, a pathogenic/likely pathogenic variant was identified in five (two patients from the same family) of 27 HH cases (two novel) and three of the six Hh. In HH group variants (pathogenic, likely pathogenic and variant of uncertain significance) were identified in KISS1R (n=2), PROK2 (n=1), FGFR1 (n=1), HS6ST1 (n=1), GNRH1 (n=1) genes. In the Hh group, splice-site mutations were detected in DCAF17 (n=1) and MCM9 (n=2) genes. Conclusions HH and Hh cases are genetically heterogeneous diseases due to oligogenic inheritance, incomplete penetrance, and variable expressivity. We found rare variants in CHH related genes in half of our HH cases, whereas they classified as pathogenic/likely pathogenic according to ACMG criteria in only about 15\\% of HH cases. Using advanced genetic analysis methods such as whole-genome sequencing and long-read sequencing may increase the mutation detection rate, which should always be associated with and expert genetic counseling to interpret the data.},\n\tlanguage = {en},\n\turldate = {2021-05-20},\n\tjournal = {Journal of Pediatric Endocrinology and Metabolism},\n\tauthor = {Turkyilmaz, Ayberk and Cayir, Atilla and Yarali, Oguzhan and Kurnaz, Erdal and Baykan, Emine Kartal and Ates, Esra Arslan and Demirbilek, Huseyin},\n\tmonth = apr,\n\tyear = {2021},\n\tnote = {Publisher: De Gruyter\nSection: Journal of Pediatric Endocrinology and Metabolism},\n}\n\n

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\n \n\n \n \n \n \n \n A Model-Strengthened Imaging Biomarker for Survival Prediction in EGFR-Mutated Non-small-cell Lung Carcinoma Patients Treated with Tyrosine Kinase Inhibitors.\n \n \n \n\n\n \n Collin, A.; Groza, V.; Missenard, L.; Chomy, F.; Colin, T.; Palussière, J.; and Saut, O.\n\n\n \n\n\n\n Bulletin of Mathematical Biology, 83(6): 68. May 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 4 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{collin_model-strengthened_2021,\n\ttitle = {A {Model}-{Strengthened} {Imaging} {Biomarker} for {Survival} {Prediction} in {EGFR}-{Mutated} {Non}-small-cell {Lung} {Carcinoma} {Patients} {Treated} with {Tyrosine} {Kinase} {Inhibitors}},\n\tvolume = {83},\n\tissn = {1522-9602},\n\tdoi = {10.1007/s11538-021-00902-7},\n\tabstract = {Non-small-cell lung carcinoma is a frequent type of lung cancer with a bad prognosis. Depending on the stage and genomics, several therapeutical approaches are used. Tyrosine Kinase Inhibitors (TKI) may be successful for a time in the treatment of EGFR-mutated non-small cells lung carcinoma. Our objective is here to introduce a survival assessment as their efficacy in the long run is challenging to evaluate. The study includes 17 patients diagnosed with EGFR-mutated non-small cell lung cancer and exposed to an EGFR-targeting TKI with 3 computed tomography (CT) scans of the primary tumor (one before the TKI introduction and two after). An imaging biomarker based on evolution of texture heterogeneity between the first and the third exams is derived and computed from a mathematical model and patient data. Defining the overall survival as the time between the introduction of the TKI treatment and the patient death, we obtain a statistically significant correlation between the overall survival and our imaging marker ([Formula: see text]). Using the ROC curve, the patients are separated into two populations and the comparison of the survival curves is statistically significant ([Formula: see text]). The baseline exam seems to have a significant role in the prediction of response to TKI treatment. More precisely, our imaging biomarker defined using only the CT scan before the TKI introduction allows to determine a first classification of the population which is improved over time using the imaging marker as soon as more CT scans are available. This exploratory study leads us to think that it is possible to obtain a survival assessment using only few CT scans of the primary tumor.},\n\tlanguage = {eng},\n\tnumber = {6},\n\tjournal = {Bulletin of Mathematical Biology},\n\tauthor = {Collin, Annabelle and Groza, Vladimir and Missenard, Louise and Chomy, François and Colin, Thierry and Palussière, Jean and Saut, Olivier},\n\tmonth = may,\n\tyear = {2021},\n\tpmid = {33966172},\n\tkeywords = {EGFR, Imaging biomarker, Mathematical modeling, Survival assessment, TKI},\n\tpages = {68},\n}\n\n

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\n \n\n \n \n \n \n \n \n Small Cell Lung Cancer Transformation as a Resistance Mechanism to Osimertinib in Epidermal Growth Factor Receptor-Mutated Lung Adenocarcinoma: Case Report and Literature Review.\n \n \n \n \n\n\n \n Leonetti, A.; Minari, R.; Mazzaschi, G.; Gnetti, L.; La Monica, S.; Alfieri, R.; Campanini, N.; Verzè, M.; Olivani, A.; Ventura, L.; and Tiseo, M.\n\n\n \n\n\n\n Frontiers in Oncology, 11. April 2021.\n Publisher: Frontiers\n\n\n\n
\n\n\n\n \n \n $\"Small$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{leonetti_small_2021,\n\ttitle = {Small {Cell} {Lung} {Cancer} {Transformation} as a {Resistance} {Mechanism} to {Osimertinib} in {Epidermal} {Growth} {Factor} {Receptor}-{Mutated} {Lung} {Adenocarcinoma}: {Case} {Report} and {Literature} {Review}},\n\tvolume = {11},\n\tissn = {2234-943X},\n\tshorttitle = {Small {Cell} {Lung} {Cancer} {Transformation} as a {Resistance} {Mechanism} to {Osimertinib} in {Epidermal} {Growth} {Factor} {Receptor}-{Mutated} {Lung} {Adenocarcinoma}},\n\turl = {https://www.frontiersin.org/articles/10.3389/fonc.2021.642190/full},\n\tdoi = {10.3389/fonc.2021.642190},\n\tabstract = {Introduction: Small-cell lung cancer (SCLC) transformation represents a mechanism of resistance to osimertinib in EGFR-mutated lung adenocarcinoma, which dramatically impact patients’ prognosis due to the high refractoriness to conventional treatments. Case description: We present the case of a patient who developed a SCLC phenotypic transformation as resistance mechanism to second-line osimertinib for T790M-positive EGFR-mutated NSCLC. Our patient received platinum-etoposide doublet following SCLC switch and achieved a modest clinical benefit which lasted four months. NGS and IHC analyses for p53 and Rb were performed on subsequent liver biopsies, revealing baseline TP53 mutation and complete absence of p53 and Rb expression. Primary cell cultures were established following a liver biopsy at the time of SCLC transformation and drug sensitivity assays showed a meaningful cell growth inhibition when osimertinib was added to platinum-etoposide compared to control (p{\\textless}0.05). A review of the current literature regarding SCLC transformation after failure of osimertinib was performed. Conclusions: Based on retrospective data available to date, platinum-etoposide chemotherapy is the preferred treatment choice in the occurrence of SCLC transformation after osimertinib failure. The extension of osimertinib in combination with chemotherapy in the occurrence of SCLC transformation as resistance mechanism to osimertinib is a matter of debate. The combination of osimertinib and platinum-etoposide was effective in inhibiting cell growth in our primary cell cultures. Clinical studies are needed to further explore this combination in the occurrence of SCLC transformation as a resistance mechanism to osimertinib.},\n\tlanguage = {English},\n\turldate = {2021-05-06},\n\tjournal = {Frontiers in Oncology},\n\tauthor = {Leonetti, Alessandro and Minari, Roberta and Mazzaschi, Giulia and Gnetti, Letizia and La Monica, Silvia and Alfieri, Roberta and Campanini, Nicoletta and Verzè, Michela and Olivani, Andrea and Ventura, Luigi and Tiseo, Marcello},\n\tmonth = apr,\n\tyear = {2021},\n\tnote = {Publisher: Frontiers},\n\tkeywords = {Case report, EGFR, NSCLC, Osimertinib resistance, Phenotype switch, SCLC transformation, STS},\n}\n\n

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\n \n\n \n \n \n \n \n Biallelic variants in the SORD gene are one of the most common causes of hereditary neuropathy among Czech patients.\n \n \n \n\n\n \n Laššuthová, P.; Mazanec, R.; Staněk, D.; Sedláčková, L.; Plevová, B.; Haberlová, J.; and Seeman, P.\n\n\n \n\n\n\n Scientific Reports, 11(1): 8443. April 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{lassuthova_biallelic_2021,\n\ttitle = {Biallelic variants in the {SORD} gene are one of the most common causes of hereditary neuropathy among {Czech} patients},\n\tvolume = {11},\n\tissn = {2045-2322},\n\tdoi = {10.1038/s41598-021-86857-0},\n\tabstract = {Recently, biallelic variants in the SORD gene were identified as causal for axonal hereditary neuropathy (HN). We ascertained the spectrum and frequency of SORD variants among a large cohort of Czech patients with unknown cause of HN. Exome sequencing data were analysed for SORD (58 patients). The prevalent c.757del variant was tested with fragment analysis (931 patients). Sanger sequencing in additional 70 patients was done. PCR primers were designed to amplify the SORD gene with the exclusion of the pseudogene SORD2P. Sequence differences between gene and pseudogene were identified and frequencies of SNPs were calculated. Eighteen patients from 16 unrelated families with biallelic variants in the SORD gene were found and the c.757del was present in all patients on at least one allele. Three novel, probably pathogenic, variants were detected, always in a heterozygous state in combination with the c.757del on the second allele. Patients presented with a slowly progressive axonal HN. Almost all patients had moderate pes cavus deformity. SORD neuropathy is frequent in Czech patients and the third most common cause of autosomal recessive HN. The c.757del is highly prevalent. Specific amplification of the SORD gene with the exclusion of the pseudogene is essential for a precise molecular diagnostics.},\n\tlanguage = {eng},\n\tnumber = {1},\n\tjournal = {Scientific Reports},\n\tauthor = {Laššuthová, P. and Mazanec, R. and Staněk, D. and Sedláčková, L. and Plevová, B. and Haberlová, J. and Seeman, P.},\n\tmonth = apr,\n\tyear = {2021},\n\tpmid = {33875678},\n\tkeywords = {Alamut, Hereditary Disorders, Neuropathy},\n\tpages = {8443},\n}\n\n

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\n \n\n \n \n \n \n \n \n The Molecular Landscape of Primary Acral Melanoma: A Multicenter Study of the Italian Melanoma Intergroup (IMI).\n \n \n \n \n\n\n \n Elefanti, L.; Zamuner, C.; Del Fiore, P.; Stagni, C.; Pellegrini, S.; Dall’Olmo, L.; Fabozzi, A.; Senetta, R.; Ribero, S.; Salmaso, R.; Mocellin, S.; Bassetto, F.; Cavallin, F.; Tosi, A. L.; Galuppini, F.; Dei Tos, A. P.; Menin, C.; and Cappellesso, R.\n\n\n \n\n\n\n International Journal of Molecular Sciences, 22(8): 3826. April 2021.\n Number: 8 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"The$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{elefanti_molecular_2021,\n\ttitle = {The {Molecular} {Landscape} of {Primary} {Acral} {Melanoma}: {A} {Multicenter} {Study} of the {Italian} {Melanoma} {Intergroup} ({IMI})},\n\tvolume = {22},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tshorttitle = {The {Molecular} {Landscape} of {Primary} {Acral} {Melanoma}},\n\turl = {https://www.mdpi.com/1422-0067/22/8/3826},\n\tdoi = {10.3390/ijms22083826},\n\tabstract = {Acral melanoma (AM) is a rare and aggressive subtype of melanoma affecting the palms, soles, and nail apparatus with similar incidence among different ethnicities. AM is unrelated to ultraviolet radiation and has a low mutation burden but frequent chromosomal rearrangements and gene amplifications. Next generation sequencing of 33 genes and somatic copy number variation (CNV) analysis with genome-wide single nucleotide polymorphism arrays were performed in order to molecularly characterize 48 primary AMs of Italian patients in association with clinicopathological and prognostic features. BRAF was the most commonly mutated gene, followed by NRAS and TP53, whereas TERT promoter, KIT, and ARID1A were less frequently mutated. Gains and losses were recurrently found in the 1q, 6p, 7, 8q, 20 and 22 chromosomes involving PREX2, RAC1, KMT2C, BRAF, CCND1, TERT, and AKT3 genes, and in the 6q, 9, 10, 11q and 16q chromosomes including CDKN2A, PTEN, and ADAMTS18 genes, respectively. This study confirmed the variety of gene mutations and the high load of CNV in primary AM. Some genomic alterations were associated with histologic prognostic features. BRAF mutations, found with a higher rate than previously reported, correlated with a low Breslow thickness, low mitotic count, low CNV of the AMs, and with early-stage of disease.},\n\tlanguage = {en},\n\tnumber = {8},\n\turldate = {2021-04-23},\n\tjournal = {International Journal of Molecular Sciences},\n\tauthor = {Elefanti, Lisa and Zamuner, Carolina and Del Fiore, Paolo and Stagni, Camilla and Pellegrini, Stefania and Dall’Olmo, Luigi and Fabozzi, Alessio and Senetta, Rebecca and Ribero, Simone and Salmaso, Roberto and Mocellin, Simone and Bassetto, Franco and Cavallin, Francesco and Tosi, Anna Lisa and Galuppini, Francesca and Dei Tos, Angelo Paolo and Menin, Chiara and Cappellesso, Rocco},\n\tmonth = apr,\n\tyear = {2021},\n\tnote = {Number: 8\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {ARID1A, BRAF, KIT, NRAS, PREX2, SOPHiA DDM, TERT promoter, TP53, acral melanoma, copy number variations},\n\tpages = {3826},\n}\n\n

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\n \n\n \n \n \n \n \n \n New dead/H-box helicase gene (ddx41) mutation in an Italian family with recurrent leukemia.\n \n \n \n \n\n\n \n Fazio, F.; Quintini, M.; Carmosino, I.; Matteucci, C.; Miulli, E.; Pellanera, F.; Lucani, B.; Ansuinelli, M.; Breccia, M.; Mecucci, C.; and Latagliata, R.\n\n\n \n\n\n\n Leukemia & Lymphoma, 0(0): 1–4. April 2021.\n Publisher: Taylor & Francis _eprint: https://doi.org/10.1080/10428194.2021.1910689\n\n\n\n
\n\n\n\n \n \n $\"New$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{fazio_new_2021,\n\ttitle = {New dead/{H}-box helicase gene (ddx41) mutation in an {Italian} family with recurrent leukemia},\n\tvolume = {0},\n\tissn = {1042-8194},\n\turl = {https://doi.org/10.1080/10428194.2021.1910689},\n\tdoi = {10.1080/10428194.2021.1910689},\n\tnumber = {0},\n\turldate = {2021-04-23},\n\tjournal = {Leukemia \\& Lymphoma},\n\tauthor = {Fazio, Francesca and Quintini, Martina and Carmosino, Ida and Matteucci, Caterina and Miulli, Eleonora and Pellanera, Fabrizia and Lucani, Benedetta and Ansuinelli, Michela and Breccia, Massimo and Mecucci, Cristina and Latagliata, Roberto},\n\tmonth = apr,\n\tyear = {2021},\n\tpmid = {33836623},\n\tnote = {Publisher: Taylor \\& Francis\n\\_eprint: https://doi.org/10.1080/10428194.2021.1910689},\n\tkeywords = {Leukemia},\n\tpages = {1--4},\n}\n\n

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\n \n\n \n \n \n \n \n \n Clinical and Genetic Heterogeneity in a Large Family with Pseudoxanthoma Elasticum: MTHFR and SERPINE1 Variants as Possible Disease Modifiers in Developing Ischemic Stroke.\n \n \n \n \n\n\n \n Bruno, G.; Ritelli, M.; Di Pietro, A.; Cipriano, L.; Colombi, M.; Lus, G.; and Puoti, G.\n\n\n \n\n\n\n Journal of Stroke and Cerebrovascular Diseases, 30(6): 105744. April 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Clinical$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{bruno_clinical_2021,\n\ttitle = {Clinical and {Genetic} {Heterogeneity} in a {Large} {Family} with {Pseudoxanthoma} {Elasticum}: {MTHFR} and {SERPINE1} {Variants} as {Possible} {Disease} {Modifiers} in {Developing} {Ischemic} {Stroke}},\n\tvolume = {30},\n\tissn = {1052-3057},\n\tshorttitle = {Clinical and {Genetic} {Heterogeneity} in a {Large} {Family} with {Pseudoxanthoma} {Elasticum}},\n\turl = {https://www.sciencedirect.com/science/article/pii/S1052305721001476},\n\tdoi = {10.1016/j.jstrokecerebrovasdis.2021.105744},\n\tabstract = {Background and objectives\nPseudoxanthoma elasticum (PXE) is a rare autosomal recessive disorder caused by pathogenic variants in the ABCC6 gene. The phenotypic spectrum of PXE is highly variable and includes principally three major features: skin lesions, eye and vascular manifestations, while brain manifestations are less common. To date about 400 different PXE associated variants in ABCC6 gene are described without any evident genotype–phenotype correlation. Herein, we report the clinical and molecular findings of a large PXE family with clinical and genetic intra-familial variability with significant cerebrovascular involvement.\nMethods\nThe analysis of the ABCC6 gene was performed in the proband and her familiars for the definition of genetic background. Then, in order to determine why some affected individuals had more prominent brain involvement, we investigated classic thrombophilic gene variants.\nResults\nMolecular findings disclosed two different ABCC6 mutations, i.e., the recurrent p.(Arg518Gln) and the novel p.(Val1285Met) missense substitution responsible of a pseudo-dominant inheritance. The study of thrombophilic gene variants revealed the presence of 4G/4G SERPINE1 genotype in the proband and in her father, which both developed ischemic stroke. The proband carried also the C677T variant the MTHFR gene.\nConclusion\nWe argue, for the first time, that the 4G/4G SERPINE1 genotype could represent an additional risk factor in PXE for developing ischemic stroke, which adds up to the already known predisposing conditions. Therapeutic implications are discussed, we also advise that PXE patients should be adequately screened for cerebral vasculopathy, even more if familial history is suggestive of brain complications.},\n\tlanguage = {en},\n\tnumber = {6},\n\turldate = {2021-04-06},\n\tjournal = {Journal of Stroke and Cerebrovascular Diseases},\n\tauthor = {Bruno, Giorgia and Ritelli, Marco and Di Pietro, Andrea and Cipriano, Lorenzo and Colombi, Marina and Lus, Giacomo and Puoti, Gianfranco},\n\tmonth = apr,\n\tyear = {2021},\n\tkeywords = {4G/5G, Alamut, MTHFR C677T, PAI-1, Pseudoxanthoma elasticum, SERPINE1, SOPHiA DDM, Stroke, Thrombophilia},\n\tpages = {105744},\n}\n\n

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\n \n\n \n \n \n \n \n \n Pharmacological Inhibition of WIP1 Sensitizes Acute Myeloid Leukemia Cells to the MDM2 Inhibitor Nutlin-3a.\n \n \n \n \n\n\n \n Fontana, M. C.; Nanni, J.; Ghelli Luserna di Rorà, A.; Petracci, E.; Padella, A.; Ghetti, M.; Ferrari, A.; Marconi, G.; Soverini, S.; Iacobucci, I.; Papayannidis, C.; Curti, A.; Audisio, E.; Giannini, M. B.; Rondoni, M.; Lanza, F.; Cavo, M.; Martinelli, G.; and Simonetti, G.\n\n\n \n\n\n\n Biomedicines, 9(4): 388. April 2021.\n Number: 4 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Pharmacological$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{fontana_pharmacological_2021,\n\ttitle = {Pharmacological {Inhibition} of {WIP1} {Sensitizes} {Acute} {Myeloid} {Leukemia} {Cells} to the {MDM2} {Inhibitor} {Nutlin}-3a},\n\tvolume = {9},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\turl = {https://www.mdpi.com/2227-9059/9/4/388},\n\tdoi = {10.3390/biomedicines9040388},\n\tabstract = {In acute myeloid leukemia (AML), the restoration of p53 activity through MDM2 inhibition proved efficacy in combinatorial therapies. WIP1, encoded from PPM1D, is a negative regulator of p53. We evaluated PPM1D expression and explored the therapeutic efficacy of WIP1 inhibitor (WIP1i) GSK2830371, in association with the MDM2 inhibitor Nutlin-3a (Nut-3a) in AML cell lines and primary samples. PPM1D transcript levels were higher in young patients compared with older ones and in core-binding-factor AML compared with other cytogenetic subgroups. In contrast, its expression was reduced in NPM1-mutated (mut, irrespective of FLT3-ITD status) or TP53-mut cases compared with wild-type (wt) ones. Either Nut-3a, and moderately WIP1i, as single agent decreased cell viability of TP53-wt cells (MV-4-11, MOLM-13, OCI-AML3) in a time/dosage-dependent manner, but not of TP53-mut cells (HEL, KASUMI-1, NOMO-1). The drug combination synergistically reduced viability and induced apoptosis in TP53-wt AML cell line and primary cells, but not in TP53-mut cells. Gene expression and immunoblotting analyses showed increased p53, MDM2 and p21 levels in treated TP53-wt cells and highlighted the enrichment of MYC, PI3K-AKT-mTOR and inflammation-related signatures upon WIP1i, Nut-3a and their combination, respectively, in the MV-4-11 TP53-wt model. This study demonstrated that WIP1 is a promising therapeutic target to enhance Nut-3a efficacy in TP53-wt AML.},\n\tlanguage = {en},\n\tnumber = {4},\n\turldate = {2021-04-12},\n\tjournal = {Biomedicines},\n\tauthor = {Fontana, Maria Chiara and Nanni, Jacopo and Ghelli Luserna di Rorà, Andrea and Petracci, Elisabetta and Padella, Antonella and Ghetti, Martina and Ferrari, Anna and Marconi, Giovanni and Soverini, Simona and Iacobucci, Ilaria and Papayannidis, Cristina and Curti, Antonio and Audisio, Ernesta and Giannini, Maria Benedetta and Rondoni, Michela and Lanza, Francesco and Cavo, Michele and Martinelli, Giovanni and Simonetti, Giorgia},\n\tmonth = apr,\n\tyear = {2021},\n\tnote = {Number: 4\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {AML, MDM2, MYS, WIP1, novel therapeutic targets},\n\tpages = {388},\n}\n\n

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\n \n\n \n \n \n \n \n HACE1, GLRX5, and ELP2 gene variant cause spastic paraplegies.\n \n \n \n\n\n \n Sager, G.; Turkyilmaz, A.; Ates, E. A.; and Kutlubay, B.\n\n\n \n\n\n\n Acta Neurologica Belgica. April 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{sager_hace1_2021,\n\ttitle = {{HACE1}, {GLRX5}, and {ELP2} gene variant cause spastic paraplegies},\n\tissn = {2240-2993},\n\tdoi = {10.1007/s13760-021-01649-7},\n\tabstract = {Hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of conditions that are characterized by lower limb spasticity and weakness. Considering the clinical overlap between metabolic causes, genetic diseases, and autosomal recessive HSP, differentiation between these types can be difficult based solely on their clinical characteristics. This study aimed to investigate the genetic etiology of patients with clinically suspected HSP. The study group was composed of seven Turkish families who each had two affected children and three families who each had a single affected child (17 total patients). The 17 probands (14 males, 3 females) underwent whole exome sequencing. Five typical HSP genes (FA2H, AP4M1, AP4E1, CYP7B1, and MAG) and three genes not previously related to HSP (HACE1, GLRX5, ad ELP2) were identified in 14 probands. Eight novel variants were identified in seven families: c.653 T {\\textgreater} C (p.Leu218Pro) in the FA2H gene, c.347G {\\textgreater} A (p.Gly116Asp) in the GLRX5 gene, c.2581G {\\textgreater} C (p.Ala861Pro) in the HACE1 gene, c.1580G {\\textgreater} A (p.Arg527Gln) and c.1189-1G {\\textgreater} A in the ELP2 gene, c.10C {\\textgreater} T (p.Gln4*) and c.1025 + 1G {\\textgreater} A in the AP4M1 gene, c.1291delG (p.Gly431Alafs*3) and c.3250delA (p.Ile1084*) in the AP4E1 gene, and c.475 T {\\textgreater} G (p.Cys159Gly) in the MAG gene. The growing use of next-generation sequencing improved diagnosis but also led to the continual identification of new causal genes for neurogenetic diseases associated with lower limb spasticity. The increasing number of HSP genes identified thus far highlights the extreme genetic heterogeneity of these disorders and their clinical and functional overlap with other neurological conditions. Our findings suggest that the HACE1, GLRX5, and ELP2 genes are genetic causes of HSP.},\n\tlanguage = {eng},\n\tjournal = {Acta Neurologica Belgica},\n\tauthor = {Sager, Gunes and Turkyilmaz, Ayberk and Ates, Esra Arslan and Kutlubay, Busra},\n\tmonth = apr,\n\tyear = {2021},\n\tpmid = {33813722},\n\tkeywords = {ELP2, GLRX5, HACE1, Novel variant, SOPHiA DDM, Spastic paraplegia, Spasticity},\n}\n\n

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\n \n\n \n \n \n \n \n \n Biallelic Mutations in DNAJB11are Associated with Prenatal Polycystic Kidney Disease in a Turkish Family.\n \n \n \n \n\n\n \n Ateş, E. A.; Turkyilmaz, A.; Delil, K.; Alavanda, C.; Söylemez, M. A.; Geçkinli, B. B.; Ata, P.; and Arman, A.\n\n\n \n\n\n\n Molecular Syndromology,1–7. April 2021.\n Publisher: Karger Publishers\n\n\n\n
\n\n\n\n \n \n $\"Biallelic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{ates_biallelic_2021,\n\ttitle = {Biallelic {Mutations} in {DNAJB11are} {Associated} with {Prenatal} {Polycystic} {Kidney} {Disease} in a {Turkish} {Family}},\n\tissn = {1661-8769, 1661-8777},\n\turl = {https://www.karger.com/Article/FullText/513611},\n\tdoi = {10.1159/000513611},\n\tabstract = {Polycystic kidney disease (PKD) is a life-threatening condition resulting in end-stage renal disease. Two major forms of PKD are defined according to the inheritance pattern. Autosomal dominant PKD (ADPKD) is characterized by renal cysts, where nearly half of the patients suffers from renal failure in the 7th decade of life. Autosomal recessive PKD (ARPKD) is a rarer and more severe form presenting in childhood. Whole-exome sequencing (WES) analyses was performed to investigate molecular causes of the disease in the fetus. In this study, we present 2 fetuses prenatally diagnosed with PKD in a consanguineous family. WES analysis of the second fetus revealed a homozygous variant (c.740+1G\\&\\#x3e;A) in \\textit{DNAJB11} which is related to ADPKD. This study reveals that \\textit{DNAJB11} biallelic mutations may cause an antenatal severe form of ARPKD and contributes to understanding the \\textit{DNAJB11}-related ADPKD phenotype. The possibility of ARPKD due to biallelic mutations in ADPKD genes should be considered in genetic counseling.},\n\tlanguage = {english},\n\turldate = {2021-04-06},\n\tjournal = {Molecular Syndromology},\n\tauthor = {Ateş, Esra Arslan and Turkyilmaz, Ayberk and Delil, Kenan and Alavanda, Ceren and Söylemez, Mehmet Ali and Geçkinli, Bilgen Bilge and Ata, Pinar and Arman, Ahmet},\n\tmonth = apr,\n\tyear = {2021},\n\tnote = {Publisher: Karger Publishers},\n\tkeywords = {SOPHiA DDM},\n\tpages = {1--7},\n}\n\n

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\n \n\n \n \n \n \n \n \n Recommendations for accurate genotyping of SARS-CoV-2 using amplicon-based sequencing of clinical samples.\n \n \n \n \n\n\n \n Kubik, S.; Marques, A. C.; Xing, X.; Silvery, J.; Bertelli, C.; De Maio, F.; Pournaras, S.; Burr, T.; Duffourd, Y.; Siemens, H.; Alloui, C.; Song, L.; Wenger, Y.; Saitta, A.; Macheret, M.; Smith, E. W.; Menu, P.; Brayer, M.; Steinmetz, L. M.; Si-Mohammed, A.; Chuisseu, J.; Stevens, R.; Constantoulakis, P.; Sali, M.; Greub, G.; Tiemann, C.; Pelechano, V.; Willig, A.; and Xu, Z.\n\n\n \n\n\n\n Clinical Microbiology and Infection. April 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Recommendations$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 10 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{kubik_recommendations_2021,\n\ttitle = {Recommendations for accurate genotyping of {SARS}-{CoV}-2 using amplicon-based sequencing of clinical samples},\n\tissn = {1198-743X},\n\turl = {https://www.sciencedirect.com/science/article/pii/S1198743X21001646},\n\tdoi = {10.1016/j.cmi.2021.03.029},\n\tabstract = {Objectives\nSARS-CoV-2 genotyping has been instrumental to monitor viral evolution and transmission during the pandemic. The quality of the sequence data obtained from these genotyping efforts depends on several factors, including the quantity/integrity of the input material, the technology as well as laboratory-specific implementation. The current lack of guidelines for SARS-CoV-2 genotyping leads to inclusion of error-containing genome sequences in genomic epidemiology studies. We aimed at establishing clear and broadly applicable recommendations for reliable virus genotyping.\nMethods\nWe established and used a sequencing data analysis workflow that reliably identifies and removes technical artifacts, which can result in miscalls when using alternative pipelines, to process clinical samples and synthetic viral genomes with an amplicon-based genotyping approach. We evaluated the impact of experimental factors, including viral load and sequencing depth, on correct sequence determination.\nResults\nWe found that at least 1000 viral genomes are necessary to confidently detect variants in the SARS-CoV-2 genome at frequencies of 10\\% or higher. The broad applicability of our recommendations was validated in over 200 clinical samples from six independent laboratories. The genotypes we determined for clinical isolates with sufficient quality cluster by sampling location and period. Our analysis also supports the rise in frequency of 20A.EU1 and 20A.EU2, two recently reported European strains whose dissemination was facilitated by travelling during the summer of 2020.\nConclusions\nWe present much-needed recommendations for reliable determination of SARS-CoV-2 genome sequence and demonstrate their broad applicability in a large cohort of clinical samples.},\n\tlanguage = {en},\n\turldate = {2021-04-06},\n\tjournal = {Clinical Microbiology and Infection},\n\tauthor = {Kubik, Slawomir and Marques, Ana Claudia and Xing, Xiaobin and Silvery, Janine and Bertelli, Claire and De Maio, Flavio and Pournaras, Spyros and Burr, Tom and Duffourd, Yannis and Siemens, Helena and Alloui, Chakib and Song, Lin and Wenger, Yvan and Saitta, Alexandra and Macheret, Morgane and Smith, Ewan W. and Menu, Philippe and Brayer, Marion and Steinmetz, Lars M. and Si-Mohammed, Ali and Chuisseu, Josiane and Stevens, Richard and Constantoulakis, Pantelis and Sali, Michela and Greub, Gilbert and Tiemann, Carsten and Pelechano, Vicent and Willig, Adrian and Xu, Zhenyu},\n\tmonth = apr,\n\tyear = {2021},\n\tkeywords = {Amplicon, Coronavirus, Genome, Guidelines, NGS, Next-generation sequencing, Recommendations, SARS-CoV-2, SOPHiA DDM, genotyping},\n}\n\n

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\n \n\n \n \n \n \n \n \n Impact of HFE gene variants on iron overload, overall survival and leukemia-free survival in myelodysplastic syndromes.\n \n \n \n \n\n\n \n Schneeweiss-Gleixner, M.; Greiner, G.; Herndlhofer, S.; Schellnegger, J.; Krauth, M.; Gleixner, K. V; Wimazal, F.; Steinhauser, C.; Kundi, M.; Thalhammer, R.; Schwarzinger, I.; Hoermann, G.; Esterbauer, H.; Födinger, M.; Valent, P.; and Sperr, W. R\n\n\n \n\n\n\n American Journal of Cancer Research, 11(3): 955–967. March 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Impact$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{schneeweiss-gleixner_impact_2021,\n\ttitle = {Impact of {HFE} gene variants on iron overload, overall survival and leukemia-free survival in myelodysplastic syndromes},\n\tvolume = {11},\n\tissn = {2156-6976},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994158/},\n\tabstract = {Although iron overload is a clinical challenge, little is known about the clinical impact of HFE-variants in myelodysplastic syndromes (MDS) to date. We analyzed the HFE status in 167 MDS patients and 494 healthy controls. One or more of the 3 HFE-variants (H63D, C282Y, S65C) were found in 65/167 (38.9\\%) MDS patients and in 164/494 (33.2\\%) controls. At diagnosis, the median serum ferritin levels were higher in MDS patients with HFE-variants (409 µg/L; range: 23-7415) compared to those without HFE-variants (346.5 µg/L; range: 10-5450) (P=0.62). Moreover, ‘HFE-mutated’ patients had a slightly faster increase in serum ferritin in follow up examinations. The percentage of patients with HFE-variants was higher in refractory anemia (RA) (22/53=41.5\\%) or RA with ring sideroblasts (RARS) (17/39=43.6\\%) compared to RA with excess of blasts (RAEB) (16/46=34.8\\%) or RAEB in transformation (RAEB-T) (5/17=29.4\\%). Differences were also detectable when comparing low- and high-risk MDS variants defined by the World Health Organization classification. There was no significant correlation between HFE-variants and MDS-related somatic mutations. Progression-free survival was substantially longer in patients with HFE-variants compared to those without HFE-variants H63D and C282Y (P=0.089). Together, the HFE-variants H63D and C282Y are frequently detected in Austrian MDS patients. These patients have substantially higher ferritin levels at diagnosis, accumulate iron slightly faster and have a better progression-free survival than non-mutated patients.},\n\tnumber = {3},\n\turldate = {2021-04-06},\n\tjournal = {American Journal of Cancer Research},\n\tauthor = {Schneeweiss-Gleixner, Mathias and Greiner, Georg and Herndlhofer, Susanne and Schellnegger, Julia and Krauth, Maria-Theresa and Gleixner, Karoline V and Wimazal, Friedrich and Steinhauser, Corinna and Kundi, Michael and Thalhammer, Renate and Schwarzinger, Ilse and Hoermann, Gregor and Esterbauer, Harald and Födinger, Manuela and Valent, Peter and Sperr, Wolfgang R},\n\tmonth = mar,\n\tyear = {2021},\n\tpmid = {33791166},\n\tpmcid = {PMC7994158},\n\tkeywords = {MYS, Myeloid, SOPHiA DDM},\n\tpages = {955--967},\n}\n\n

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\n \n\n \n \n \n \n \n \n Ruxolitinib before allogeneic hematopoietic transplantation in patients with myelofibrosis on behalf SFGM-TC and FIM groups.\n \n \n \n \n\n\n \n Robin, M.; Porcher, R.; Orvain, C.; Bay, J.; Barraco, F.; Huynh, A.; Charbonnier, A.; Forcade, E.; Chantepie, S.; Bulabois, C.; Yakoub-Agha, I.; Detrait, M.; Michonneau, D.; Turlure, P.; Raus, N.; Boyer, F.; Suarez, F.; Vincent, L.; Guyen, S. N.; Cornillon, J.; Villate, A.; Dupriez, B.; Cassinat, B.; Rolland, V.; Schlageter, M. H.; Socié, G.; and Kiladjian, J.\n\n\n \n\n\n\n Bone Marrow Transplantation,1–12. March 2021.\n Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"Ruxolitinib$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{robin_ruxolitinib_2021,\n\ttitle = {Ruxolitinib before allogeneic hematopoietic transplantation in patients with myelofibrosis on behalf {SFGM}-{TC} and {FIM} groups},\n\tcopyright = {2021 The Author(s), under exclusive licence to Springer Nature Limited},\n\tissn = {1476-5365},\n\turl = {https://www.nature.com/articles/s41409-021-01252-7},\n\tdoi = {10.1038/s41409-021-01252-7},\n\tabstract = {This multicenter prospective phase 2 trial analyzed disease-free survival (DFS) in myelofibrosis patients receiving ruxolitinib for 6 months before transplantation. Seventy-six patients were recruited. Age-adjusted dynamic international prognostic scoring system was intermediate-1, intermediate-2, and high in 27 (36\\%), 31 (41\\%), and 18 (24\\%) patients. All patients received ruxolitinib from inclusion to conditioning regimen (fludarabine-melphalan) or to progression. A donor was found in 64 patients: 18 HLA-matched sibling donor (MSD), 32 HLA-matched unrelated (UD10/10), and 14 HLA mismatched unrelated donor (UD9/10. Among 64 patients with a donor, 20 (31\\%) achieved a partial response before transplantation and 59 (92\\%) could be transplanted after ruxolitinib therapy (18/18 MSD, 30/21 UD10/10, 11/34 UD9/10), of whom 19 (32\\%) were splenectomized. Overall survival from inclusion was 68\\% at 12 months. One-year DFS after transplantation was 55\\%: 83\\%, 40\\%, and 34\\% after MSD, UD10/10 or UD9/10, respectively. Cumulative incidence of grade 2–4 acute graft-versus-host disease (GVHD) was 66\\% and non-relapse-mortality was 42\\% at 12 months. Short course of ruxolitinib before transplantation is followed by a high rate of transplantation. With the platform used in this protocol, outcome was much better in patients transplanted with HLA-matched sibling donor as compared to unrelated donor.},\n\tlanguage = {en},\n\turldate = {2021-03-30},\n\tjournal = {Bone Marrow Transplantation},\n\tauthor = {Robin, Marie and Porcher, Raphael and Orvain, Corentin and Bay, Jacques-Olivier and Barraco, Fiorenza and Huynh, Anne and Charbonnier, Amandine and Forcade, Edouard and Chantepie, Sylvain and Bulabois, Claude and Yakoub-Agha, Ibrahim and Detrait, Marie and Michonneau, David and Turlure, Pascal and Raus, Nicole and Boyer, Françoise and Suarez, Felipe and Vincent, Laure and Guyen, Stéphanie N. and Cornillon, Jérôme and Villate, Alban and Dupriez, Brigitte and Cassinat, Bruno and Rolland, Valérie and Schlageter, Marie Hélène and Socié, Gérard and Kiladjian, Jean-Jacques},\n\tmonth = mar,\n\tyear = {2021},\n\tnote = {Publisher: Nature Publishing Group},\n\tkeywords = {Custom Panel, SOPHiA DDM},\n\tpages = {1--12},\n}\n\n

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\n \n\n \n \n \n \n \n \n Screening of MC4R, LEP, LEPR, POMC, SH2B1, and SIM1 genes in Turkish children with severe early-onset obesity.\n \n \n \n \n\n\n \n Turkyilmaz, A.; Yarali, O.; Kurnaz, E.; and Cayir, A.\n\n\n \n\n\n\n Medicine Science \\textbar International Medical Journal, 10(2): 328. March 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Screening$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{turkyilmaz_screening_2021,\n\ttitle = {Screening of {MC4R}, {LEP}, {LEPR}, {POMC}, {SH2B1}, and {SIM1} genes in {Turkish} children with severe early-onset obesity},\n\tvolume = {10},\n\tissn = {2147-0634},\n\turl = {https://www.ejmanager.com/fulltextpdf.php?mno=9419},\n\tdoi = {10.5455/medscience.2020.10.211},\n\tabstract = {The aim of this study was to determine the prevalence of leptin (LEP), leptin receptors (LEPR), melanocortin-4-receptor (MC4R), proopiomelanocortin (POMC), single-minded 1 (SIM1), and SH2B1 gene variations in Turkish children and adolescents, and to conduct a detailed examination of the clinical and laboratory findings of patients with variants. In this study, we included 49 children and adolescents (29 male/20 female) who presented to the Pediatric Endocrinology clinic of Erzurum Regional Training and Research Hospital between 2017 and 2020 with obesity. Family history with regards to obesity, parental consanguinity, obesity-related comorbidities, anthropometric measurements, and laboratory tests of the patients were recorded in the clinical evaluation. LEP, LEPR, MC4R, POMC, SIM1, and SH2B1 genes, which are associated with monogenic obesity, were evaluated by the next generation sequencing analysis in all patients. The mean age of 49 patients included in the study was 8.4 ± 5.2 years (range: 0.6–16.8), their mean height standard deviation score (SDS) was 0.9 ± 1.6, mean body mass index (BMI) was 31.3 ± 8.1 kg/m2, and their mean BMI SDS was 3.5 ± 0.6. A total of four different variants (c.380C{\\textgreater}T and c.870delG variants in MC4R gene; c.2992A{\\textgreater}C and c.448delA variants in LEPR gene) were detected in four patients. The determination of a molecular etiology in patients with monogenic obesity is important in view of the treatment options to be introduced in the near future (MC4R agonist) and for the family to receive appropriate genetic counseling. In this study, we evaluated the clinical and genetic findings of the patients with monogenic obesity in detail, and contributed the findings of the novel variants to the literature.},\n\tlanguage = {en},\n\tnumber = {2},\n\turldate = {2021-03-30},\n\tjournal = {Medicine Science {\\textbar} International Medical Journal},\n\tauthor = {Turkyilmaz, Ayberk and Yarali, Oguzhan and Kurnaz, Erdal and Cayir, Atilla},\n\tmonth = mar,\n\tyear = {2021},\n\tkeywords = {SOPHiA DDM},\n\tpages = {328},\n}\n\n

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\n \n\n \n \n \n \n \n \n New germline mutations in BRCA1, ATM, MUTYH, and RAD51D genes in Tuvans early-onset breast cancer patients.\n \n \n \n \n\n\n \n \n\n\n \n\n\n\n Experimental Oncology. March 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"New$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{noauthor_new_2021,\n\ttitle = {New germline mutations in {BRCA1}, {ATM}, {MUTYH}, and {RAD51D} genes in {Tuvans} early-onset breast cancer patients},\n\tissn = {18129269, 23128852},\n\turl = {https://exp-oncology.com.ua/article/15587/new-germline-mutations-in-i-brca1-atm-mutyh-i-and-i-rad51d-i-genes-in-tuvans-early-onset-breast-cancer-patients},\n\tdoi = {10.32471/exp-oncology.2312-8852.vol-43-no-1.15587},\n\tabstract = {Background: In Russia, more than 50,000 women are diagnosed with breast cancer (BC) every year. Russia is a multinational country — about 200 ethnic groups live on its territory. Khakass, Buryats, Tuvans and other ethnic groups show higher rate of increase in BC incidence and a younger age of first diagnosed BC compared to Caucasian ethnicities. We focused on Tuvan ethnic group to find specific genetic aberrations associated with BC. There are no BC prevention models as well as standards for the treatment of inherited BC in Tuvans. In this context, the search for genetic markers of early cancer detection and the development of criteria for therapy response are relevant. Aim: To identify hereditary mutations in BC-associated genes in Tuvan women. Materials and Methods: 24 patients with early-onset BC (range, 25 to 46 years) were enrolled in the study. Genomic DNA isolated from blood samples was used to prepare libraries using a capture-based target enrichment kit covering 27 genes (ATM, APC, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, FAM175A, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PALB2, PIK3CA, PMS2, PMS2CL, PTEN, RAD50, RAD51C, RAD51D, STK11, TP53 and XRCC2). Next-generation sequencing was performed using the Illumina NextSeq500 System. Results: In our study, one pathogenic mutation was detected in BRCA1 (rs80357868) gene (prevalence of 4\\%, 1/24). We identified the truncating 3875\\_3878delGTCT mutation of BRCA1 gene in Tuvans BC patient aged 34 years. We also detected three mutations that were probably damaging by PolyPhen2 and/or deleterious by SIFT in ATM (rs781023264), MUTYH (rs199840380) and RAD51D (rs145309168) genes. Conclusion: To the best of our knowledge, this is the first report that describes the highly pathogenic variant in the BRCA1 gene (rs80357868) and possibly damaging (PolyPhen2) germline variants in the ATM (rs781023264), MUTYH (rs199840380) and RAD51D (rs145309168) genes in young Tuvans BC patient.},\n\tlanguage = {en},\n\turldate = {2021-03-30},\n\tjournal = {Experimental Oncology},\n\tmonth = mar,\n\tyear = {2021},\n\tkeywords = {HCS, SOPHiA DDM},\n}\n\n

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\n \n\n \n \n \n \n \n \n Comparison of the diagnostic yield of aCGH and genome-wide sequencing across different neurodevelopmental disorders.\n \n \n \n \n\n\n \n Martinez-Granero, F.; Blanco-Kelly, F.; Sanchez-Jimeno, C.; Avila-Fernandez, A.; Arteche, A.; Bustamante-Aragones, A.; Rodilla, C.; Rodríguez-Pinilla, E.; Riveiro-Alvarez, R.; Tahsin-Swafiri, S.; Trujillo-Tiebas, M. J.; Ayuso, C.; Rodríguez de Alba, M.; Lorda-Sanchez, I.; and Almoguera, B.\n\n\n \n\n\n\n npj Genomic Medicine, 6(1): 1–12. March 2021.\n Number: 1 Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"Comparison$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{martinez-granero_comparison_2021,\n\ttitle = {Comparison of the diagnostic yield of {aCGH} and genome-wide sequencing across different neurodevelopmental disorders},\n\tvolume = {6},\n\tcopyright = {2021 The Author(s)},\n\tissn = {2056-7944},\n\turl = {https://www.nature.com/articles/s41525-021-00188-7},\n\tdoi = {10.1038/s41525-021-00188-7},\n\tabstract = {Most consensus recommendations for the genetic diagnosis of neurodevelopmental disorders (NDDs) do not include the use of next generation sequencing (NGS) and are still based on chromosomal microarrays, such as comparative genomic hybridization array (aCGH). This study compares the diagnostic yield obtained by aCGH and clinical exome sequencing in NDD globally and its spectrum of disorders. To that end, 1412 patients clinically diagnosed with NDDs and studied with aCGH were classified into phenotype categories: global developmental delay/intellectual disability (GDD/ID); autism spectrum disorder (ASD); and other NDDs. These categories were further subclassified based on the most frequent accompanying signs and symptoms into isolated forms, forms with epilepsy; forms with micro/macrocephaly and syndromic forms. Two hundred and forty-five patients of the 1412 were subjected to clinical exome sequencing. Diagnostic yield of aCGH and clinical exome sequencing, expressed as the number of solved cases, was compared for each phenotype category and subcategory. Clinical exome sequencing was superior than aCGH for all cases except for isolated ASD, with no additional cases solved by NGS. Globally, clinical exome sequencing solved 20\\% of cases (versus 5.7\\% by aCGH) and the diagnostic yield was highest for all forms of GDD/ID and lowest for Other NDDs (7.1\\% versus 1.4\\% by aCGH) and ASD (6.1\\% versus 3\\% by aCGH). In the majority of cases, diagnostic yield was higher in the phenotype subcategories than in the mother category. These results suggest that NGS could be used as a first-tier test in the diagnostic algorithm of all NDDs followed by aCGH when necessary.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2021-03-30},\n\tjournal = {npj Genomic Medicine},\n\tauthor = {Martinez-Granero, Francisco and Blanco-Kelly, Fiona and Sanchez-Jimeno, Carolina and Avila-Fernandez, Almudena and Arteche, Ana and Bustamante-Aragones, Ana and Rodilla, Cristina and Rodríguez-Pinilla, Elvira and Riveiro-Alvarez, Rosa and Tahsin-Swafiri, Saoud and Trujillo-Tiebas, Maria Jose and Ayuso, Carmen and Rodríguez de Alba, Marta and Lorda-Sanchez, Isabel and Almoguera, Berta},\n\tmonth = mar,\n\tyear = {2021},\n\tnote = {Number: 1\nPublisher: Nature Publishing Group},\n\tkeywords = {Benchmark, CES, Neurological Phenotype},\n\tpages = {1--12},\n}\n\n

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\n \n\n \n \n \n \n \n \n A Novel Truncating Mutation in HOMER2 Causes Nonsyndromic Progressive DFNA68 Hearing Loss in a Spanish Family.\n \n \n \n \n\n\n \n Lachgar, M.; Morín, M.; Villamar, M.; del Castillo, I.; and Moreno-Pelayo, M. Á.\n\n\n \n\n\n\n Genes, 12(3): 411. March 2021.\n Number: 3 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{lachgar_novel_2021,\n\ttitle = {A {Novel} {Truncating} {Mutation} in {HOMER2} {Causes} {Nonsyndromic} {Progressive} {DFNA68} {Hearing} {Loss} in a {Spanish} {Family}},\n\tvolume = {12},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\turl = {https://www.mdpi.com/2073-4425/12/3/411},\n\tdoi = {10.3390/genes12030411},\n\tabstract = {Nonsyndromic hereditary hearing loss is a common sensory defect in humans that is clinically and genetically highly heterogeneous. So far, 122 genes have been associated with this disorder and 50 of them have been linked to autosomal dominant (DFNA) forms like DFNA68, a rare subtype of hearing impairment caused by disruption of a stereociliary scaffolding protein (HOMER2) that is essential for normal hearing in humans and mice. In this study, we report a novel HOMER2 variant (c.832\\_836delCCTCA) identified in a Spanish family by using a custom NGS targeted gene panel (OTO-NGS-v2). This frameshift mutation produces a premature stop codon that may lead in the absence of NMD to a shorter variant (p.Pro278Alafs*10) that truncates HOMER2 at the CDC42 binding domain (CBD) of the coiled-coil structure, a region that is essential for protein multimerization and HOMER2-CDC42 interaction. c.832\\_836delCCTCA mutation is placed close to the previously identified c.840\\_840dup mutation found in a Chinese family that truncates the protein (p.Met281Hisfs*9) at the CBD. Functional assessment of the Chinese mutant revealed decreased protein stability, reduced ability to multimerize, and altered distribution pattern in transfected cells when compared with wild-type HOMER2. Interestingly, the Spanish and Chinese frameshift mutations might exert a similar effect at the protein level, leading to truncated mutants with the same Ct aberrant protein tail, thus suggesting that they can share a common mechanism of pathogenesis. Indeed, age-matched patients in both families display quite similar hearing loss phenotypes consisting of early-onset, moderate-to-profound progressive hearing loss. In summary, we have identified the third variant in HOMER2, which is the first one identified in the Spanish population, thus contributing to expanding the mutational spectrum of this gene in other populations, and also to clarifying the genotype–phenotype correlations of DFNA68 hearing loss.},\n\tlanguage = {en},\n\tnumber = {3},\n\turldate = {2021-03-22},\n\tjournal = {Genes},\n\tauthor = {Lachgar, María and Morín, Matías and Villamar, Manuela and del Castillo, Ignacio and Moreno-Pelayo, Miguel Ángel},\n\tmonth = mar,\n\tyear = {2021},\n\tnote = {Number: 3\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {CDC42, Custom Panel, HOMER2, SOPHiA DDM, hereditary hearing loss, next-generation sequencing, predictive biomarkers},\n\tpages = {411},\n}\n\n

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\n \n\n \n \n \n \n \n \n Sanger sequencing is no longer always necessary based on a single-center validation of 1109 NGS variants in 825 clinical exomes.\n \n \n \n \n\n\n \n Arteche-López, A.; Ávila-Fernández, A.; Romero, R.; Riveiro-Álvarez, R.; López-Martínez, M. A.; Giménez-Pardo, A.; Vélez-Monsalve, C.; Gallego-Merlo, J.; García-Vara, I.; Almoguera, B.; Bustamante-Aragonés, A.; Blanco-Kelly, F.; Tahsin-Swafiri, S.; Rodríguez-Pinilla, E.; Minguez, P.; Lorda, I.; Trujillo-Tiebas, M. J.; and Ayuso, C.\n\n\n \n\n\n\n Scientific Reports, 11(1): 5697. March 2021.\n Number: 1 Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"Sanger$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{arteche-lopez_sanger_2021,\n\ttitle = {Sanger sequencing is no longer always necessary based on a single-center validation of 1109 {NGS} variants in 825 clinical exomes},\n\tvolume = {11},\n\tcopyright = {2021 The Author(s)},\n\tissn = {2045-2322},\n\turl = {https://www.nature.com/articles/s41598-021-85182-w},\n\tdoi = {10.1038/s41598-021-85182-w},\n\tabstract = {Despite the improved accuracy of next-generation sequencing (NGS), it is widely accepted that variants need to be validated using Sanger sequencing before reporting. Validation of all NGS variants considerably increases the turnaround time and costs of clinical diagnosis. We comprehensively assessed this need in 1109 variants from 825 clinical exomes, the largest sample set to date assessed using Illumina chemistry reported. With a concordance of 100\\%, we conclude that Sanger sequencing can be very useful as an internal quality control, but not so much as a verification method for high-quality single-nucleotide and small insertion/deletions variants. Laboratories might validate and establish their own thresholds before discontinuing Sanger confirmation studies. We also expand and validate 23 copy number variations detected by exome sequencing in 20 samples, observing a concordance of 95.65\\% (22/23).},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2021-03-16},\n\tjournal = {Scientific Reports},\n\tauthor = {Arteche-López, A. and Ávila-Fernández, A. and Romero, R. and Riveiro-Álvarez, R. and López-Martínez, M. A. and Giménez-Pardo, A. and Vélez-Monsalve, C. and Gallego-Merlo, J. and García-Vara, I. and Almoguera, Berta and Bustamante-Aragonés, A. and Blanco-Kelly, F. and Tahsin-Swafiri, S. and Rodríguez-Pinilla, E. and Minguez, P. and Lorda, I. and Trujillo-Tiebas, M. J. and Ayuso, C.},\n\tmonth = mar,\n\tyear = {2021},\n\tnote = {Number: 1\nPublisher: Nature Publishing Group},\n\tpages = {5697},\n}\n\n

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\n \n\n \n \n \n \n \n \n Unraveling Neuroendocrine Gallbladder Cancer: Comprehensive Clinicopathologic and Molecular Characterization.\n \n \n \n \n\n\n \n de Bitter, T. J. J.; Kroeze, L. I.; de Reuver, P. R.; van Vliet, S.; Vink-Börger, E.; von Rhein, D.; Jansen, E. A. M.; Nagtegaal, I. D.; Ligtenberg, M. J. L.; and van der Post, R. S.\n\n\n \n\n\n\n JCO Precision Oncology, (5): 473–484. March 2021.\n Publisher: Wolters Kluwer\n\n\n\n
\n\n\n\n \n \n $\"Unraveling$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{de_bitter_unraveling_2021,\n\ttitle = {Unraveling {Neuroendocrine} {Gallbladder} {Cancer}: {Comprehensive} {Clinicopathologic} and {Molecular} {Characterization}},\n\tshorttitle = {Unraveling {Neuroendocrine} {Gallbladder} {Cancer}},\n\turl = {https://ascopubs.org/doi/full/10.1200/PO.20.00487},\n\tdoi = {10.1200/PO.20.00487},\n\tabstract = {PURPOSENeuroendocrine carcinomas and mixed neuroendocrine non-neuroendocrine neoplasms of the gallbladder (NE GBC) are rare and highly aggressive entities. The cell of origin of NE GBC has been a matter of controversy. Here, we performed a comparative histopathologic and molecular analysis of NE GBC cases and, if present, associated precancerous lesions.PATIENTS AND METHODSWe selected cases diagnosed between 2000 and 2019 in the Netherlands. Precursors and carcinomas were immunohistochemically compared and analyzed for mutations, gene amplifications, microsatellite instability, and tumor mutational burden using an next-generation sequencing panel containing 523 cancer-related genes. In addition, presence of fusion genes was analyzed using a panel of 55 genes.RESULTSSixty percent of neuroendocrine cases (6/10) presented with a precursor lesion, either intracholecystic papillary neoplasm (n = 3) or biliary intraepithelial neoplasia (n = 3). Immunohistochemically, neuroendocrine components were different from the epithelial precursor lesions. Molecular profiling, however, revealed TP53 mutations shared between different components in five of six cases, indicating a clonal relation. Furthermore, 40\\% of cases (4/10) harbored at least one potentially actionable alteration. This included (likely) pathogenic mutations in RAD54L, ATM, and BRCA2; amplifications of ERBB2 and MDM2; and a gene fusion involving FGFR3-TACC3. All cases were microsatellite-stable and had a tumor mutational burden of {\\textless} 10 mutations/Mb.CONCLUSIONOur data provide insight into the development of NE GBC and suggest a common origin of precancerous epithelial lesions and invasive neuroendocrine components, favoring the hypothesis of lineage transformation. Moreover, nearly half of the NE GBCs carried at least one potentially actionable molecular alteration, highlighting the importance of molecular testing in this highly lethal cancer.},\n\tnumber = {5},\n\turldate = {2021-03-16},\n\tjournal = {JCO Precision Oncology},\n\tauthor = {de Bitter, Tessa J. J. and Kroeze, Leonie I. and de Reuver, Philip R. and van Vliet, Shannon and Vink-Börger, Elisa and von Rhein, Daniel and Jansen, Erik A. M. and Nagtegaal, Iris D. and Ligtenberg, Marjolijn J. L. and van der Post, Rachel S.},\n\tmonth = mar,\n\tyear = {2021},\n\tnote = {Publisher: Wolters Kluwer},\n\tkeywords = {Alamut, Cancer, SOPHiA DDM, cancer susceptibility},\n\tpages = {473--484},\n}\n\n

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\n \n\n \n \n \n \n \n \n A straightforward molecular strategy to retrospectively investigate the spread of SARS-CoV-2 VOC202012/01 B.1.1.7 variant.\n \n \n \n \n\n\n \n Ibba, G.; Sau, R.; Angioj, F.; Abbondio, M.; Rubino, S.; and Uzzau, S.\n\n\n \n\n\n\n The Journal of Infection in Developing Countries, 15(02): 242–246. March 2021.\n Number: 02\n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{ibba_straightforward_2021,\n\ttitle = {A straightforward molecular strategy to retrospectively investigate the spread of {SARS}-{CoV}-2 {VOC202012}/01 {B}.1.1.7 variant},\n\tvolume = {15},\n\tcopyright = {Copyright (c) 2021 Sergio Uzzau, Gabriele Ibba, Rosangela Sau, Flavia Angioj, Marcello Abbondio, Salvatore Rubino},\n\tissn = {1972-2680},\n\turl = {https://www.jidc.org/index.php/journal/article/view/33690207},\n\tdoi = {10.3855/jidc.14972},\n\tabstract = {The spread of new SARS-CoV-2 variants represents a serious threat worldwide, thus rapid and cost-effective methods are required for their identification. Since November 2020, the TaqPath COVID-19 assay (Thermo Fisher Scientific) has been used to identify viral strains of the new lineage B.1.1.7, since it fails to detect the S-gene with the ∆69/70 deletion. Here, we proposed S-gene mutations screening with the Allplex SARS-CoV-2 assay (Seegene), another widely used RT-PCR test that targets Sarbecovirus E, SARS-CoV-2 N, and RdRp/S genes. Accordingly, we evaluated the S gene amplification curve pattern compared to those of the other genes. Exploiting an Allplex assay-generated dataset, we screened 663 RT-PCR digital records, including all SARS-CoV-2 respiratory samples tested in our laboratory with the Allplex assay between January 1st and February 25th, 2021. This approach enabled us to detect 64 samples with peculiar non-sigmoidal amplification curves. Sequencing a selected group of 4 RNA viral genomes demonstrated that those curves were associated with B.1.1.7 variant strains. Our results strongly suggest that B.1.1.7 variant spread has begun in this area at least since January and imply the potential of these analytical methods to track and characterize the spread of B.1.1.7 strains in those areas where Allplex SARS-CoV-2 datasets have been previously recorded.},\n\tlanguage = {en},\n\tnumber = {02},\n\turldate = {2021-03-16},\n\tjournal = {The Journal of Infection in Developing Countries},\n\tauthor = {Ibba, Gabriele and Sau, Rosangela and Angioj, Flavia and Abbondio, Marcello and Rubino, Salvatore and Uzzau, Sergio},\n\tmonth = mar,\n\tyear = {2021},\n\tnote = {Number: 02},\n\tkeywords = {Molecular Diagnostics, RT-PCR, SARS-CoV-2 B.1.1.7 variant, SARSCoV-2, SOPHiA DDM},\n\tpages = {242--246},\n}\n\n

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\n \n\n \n \n \n \n \n \n Routine Molecular Screening of Patients with Advanced Non-SmallCell Lung Cancer in Circulating Cell-Free DNA at Diagnosis and During Progression Using OncoBEAMTM EGFR V2 and NGS Technologies.\n \n \n \n \n\n\n \n Garcia, J.; Gauthier, A.; Lescuyer, G.; Barthelemy, D.; Geiguer, F.; Balandier, J.; Edelstein, D. L.; Jones, F. S.; Holtrup, F.; Duruisseau, M.; Grolleau, E.; Rodriguez-Lafrasse, C.; Merle, P.; Couraud, S.; and Payen, L.\n\n\n \n\n\n\n Molecular Diagnosis & Therapy. March 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Routine$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 4 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{garcia_routine_2021,\n\ttitle = {Routine {Molecular} {Screening} of {Patients} with {Advanced} {Non}-{SmallCell} {Lung} {Cancer} in {Circulating} {Cell}-{Free} {DNA} at {Diagnosis} and {During} {Progression} {Using} {OncoBEAMTM} {EGFR} {V2} and {NGS} {Technologies}},\n\tissn = {1179-2000},\n\turl = {https://doi.org/10.1007/s40291-021-00515-9},\n\tdoi = {10.1007/s40291-021-00515-9},\n\tabstract = {The use of ultra-sensitive diagnostic tests to detect clinically actionable somatic alterations within the gene encoding the epidermal growth factor receptor (EGFR) within circulating cell-free DNA is an important first step in determining the eligibility of patients with non-small cell lung cancer to receive tyrosine kinase inhibitors.},\n\tlanguage = {en},\n\turldate = {2021-03-10},\n\tjournal = {Molecular Diagnosis \\& Therapy},\n\tauthor = {Garcia, Jessica and Gauthier, Arnaud and Lescuyer, Gaëlle and Barthelemy, David and Geiguer, Florence and Balandier, Julie and Edelstein, Daniel L. and Jones, Frederick S. and Holtrup, Frank and Duruisseau, Mickael and Grolleau, Emmanuel and Rodriguez-Lafrasse, Claire and Merle, Patrick and Couraud, Sébastien and Payen, Léa},\n\tmonth = mar,\n\tyear = {2021},\n\tkeywords = {Custom, Custom Panel, Custom Pipeline, SOPHiA DDM},\n}\n\n

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\n \n\n \n \n \n \n \n \n Prioritizing variants of uncertain significance for reclassification using a rule-based algorithm in inherited retinal dystrophies.\n \n \n \n \n\n\n \n Iancu, I.; Avila-Fernandez, A.; Arteche, A.; Trujillo-Tiebas, M. J.; Riveiro-Alvarez, R.; Almoguera, B.; Martin-Merida, I.; Del Pozo-Valero, M.; Perea-Romero, I.; Corton, M.; Minguez, P.; and Ayuso, C.\n\n\n \n\n\n\n npj Genomic Medicine, 6(1): 1–9. February 2021.\n Number: 1 Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"Prioritizing$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 4 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{iancu_prioritizing_2021,\n\ttitle = {Prioritizing variants of uncertain significance for reclassification using a rule-based algorithm in inherited retinal dystrophies},\n\tvolume = {6},\n\tcopyright = {2021 The Author(s)},\n\tissn = {2056-7944},\n\turl = {https://www.nature.com/articles/s41525-021-00182-z},\n\tdoi = {10.1038/s41525-021-00182-z},\n\tabstract = {Inherited retinal dystrophies (IRD) are a highly heterogeneous group of rare diseases with a molecular diagnostic rate of {\\textgreater}50\\%. Reclassification of variants of uncertain significance (VUS) poses a challenge for IRD diagnosis. We collected 668 IRD cases analyzed by our geneticists using two different clinical exome-sequencing tests. We identified 114 unsolved cases pending reclassification of 125 VUS and studied their genomic, functional, and laboratory-specific features, comparing them to pathogenic and likely pathogenic variants from the same cohort (N = 390). While the clinical exome used did not show differences in diagnostic rate, the more IRD-experienced geneticist reported more VUS (p = 4.07e-04). Significantly fewer VUS were reported in recessive cases (p = 2.14e-04) compared to other inheritance patterns, and of all the genes analyzed, ABCA4 and IMPG2 had the lowest and highest VUS frequencies, respectively (p = 3.89e-04, p = 6.93e-03). Moreover, few frameshift and stop-gain variants were found to be informed VUS (p = 6.73e-08 and p = 2.93e-06). Last, we applied five pathogenicity predictors and found there is a significant proof of deleteriousness when all score for pathogenicity in missense variants. Altogether, these results provided input for a set of rules that correctly reclassified {\\textasciitilde}70\\% of VUS as pathogenic in validation datasets. Disease- and setting-specific features influence VUS reporting. Comparison with pathogenic and likely pathogenic variants can prioritize VUS more likely to be reclassified as causal.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2021-03-10},\n\tjournal = {npj Genomic Medicine},\n\tauthor = {Iancu, Ionut-Florin and Avila-Fernandez, Almudena and Arteche, Ana and Trujillo-Tiebas, Maria Jose and Riveiro-Alvarez, Rosa and Almoguera, Berta and Martin-Merida, Inmaculada and Del Pozo-Valero, Marta and Perea-Romero, Irene and Corton, Marta and Minguez, Pablo and Ayuso, Carmen},\n\tmonth = feb,\n\tyear = {2021},\n\tnote = {Number: 1\nPublisher: Nature Publishing Group},\n\tkeywords = {CES, Clinical Exome, SOPHiA DDM, VUS, clinical exome sequencing, clinical genomics, variant interpretation},\n\tpages = {1--9},\n}\n\n

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\n \n\n \n \n \n \n \n \n Aldolase A deficiency: Report of new cases and literature review.\n \n \n \n \n\n\n \n Papadopoulos, C.; Svingou, M.; Kekou, K.; Vergnaud, S.; Xirou, S.; Niotakis, G.; and Papadimas, G. K.\n\n\n \n\n\n\n Molecular Genetics and Metabolism Reports, 27: 100730. March 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Aldolase$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 4 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{papadopoulos_aldolase_2021,\n\ttitle = {Aldolase {A} deficiency: {Report} of new cases and literature review},\n\tvolume = {27},\n\tissn = {2214-4269},\n\tshorttitle = {Aldolase {A} deficiency},\n\turl = {https://www.sciencedirect.com/science/article/pii/S2214426921000240},\n\tdoi = {10.1016/j.ymgmr.2021.100730},\n\tabstract = {Aldolase A (ALDOA), is the predominant isoform of aldolase in skeletal muscle and erythrocytes that catalyzes the reversibleconversion of fructose-1,6-bisphosphate to glyceraldehyde 3-phosphate. Autosomal recessive mutations in ALDOA, are extremely rare and cause hemolytic anemia and/or recurrent episodes of rhabdomyolysis, usually precipitated by fever. In this report we describe, clinical, laboratory and genetic data of two novel unrelated patients harboring mutations in the ALDOA gene who presented with episodic rhabdomyolysis, we review all previously published cases and discuss the most valuable features for diagnosis of this rare disorder.},\n\tlanguage = {en},\n\turldate = {2021-03-10},\n\tjournal = {Molecular Genetics and Metabolism Reports},\n\tauthor = {Papadopoulos, C. and Svingou, M. and Kekou, K. and Vergnaud, S. and Xirou, S. and Niotakis, G. and Papadimas, G. K.},\n\tmonth = mar,\n\tyear = {2021},\n\tkeywords = {Aldolase A, CES, Clinical Exome, Hemolytic anemia, Rhabdomyolysis, SOPHiA DDM, clinical exome sequencing, clinical genomics},\n\tpages = {100730},\n}\n\n

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\n \n\n \n \n \n \n \n A Novel ATM Pathogenic Variant in an Italian Woman with Gallbladder Cancer.\n \n \n \n\n\n \n De Paolis, E.; Urbani, A.; Salvatore, L.; Foca, L.; Tortora, G.; Minucci, A.; and Concolino, P.\n\n\n \n\n\n\n Genes, 12(2). February 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{de_paolis_novel_2021,\n\ttitle = {A {Novel} {ATM} {Pathogenic} {Variant} in an {Italian} {Woman} with {Gallbladder} {Cancer}},\n\tvolume = {12},\n\tissn = {2073-4425},\n\tdoi = {10.3390/genes12020313},\n\tabstract = {Gallbladder carcinoma (GBC) is one of the most aggressive malignancies with poor prognosis and a high fatality rate. The disease presents in advanced stages where the treatment is ineffective. Regarding GBC pathogenesis, as with other neoplasia, this tumor is a multifactorial disorder involving different causative factors such as environmental, microbial, metabolic, and molecular. Genetic alterations can be germline or somatic that involving proto-oncogenes, tumor suppressor genes, cell cycle genes, and growth factors. The ataxia telangiectasia mutated (ATM) gene, coding a serine/threonine kinase involved in the early stages of the homologous recombination (HR) mechanism, is one of the most altered genes in GBC. Here, we present the molecular characterization of a novel germline ATM large genomic rearrangement (LGR) identified by next-generation sequencing (NGS) analysis in an Italian woman diagnosed with metastatic GBC at the age of 55. The results underline the importance of expanding the NGS approach in gallbladder cancer in order to propose new molecular markers of predisposition and prognosis exploitable by novel targeted therapies that may improve the response of patients with ATM-deficient cancers.},\n\tlanguage = {eng},\n\tnumber = {2},\n\tjournal = {Genes},\n\tauthor = {De Paolis, Elisa and Urbani, Andrea and Salvatore, Lisa and Foca, Laura and Tortora, Giampaolo and Minucci, Angelo and Concolino, Paola},\n\tmonth = feb,\n\tyear = {2021},\n\tpmid = {33671809},\n\tpmcid = {PMC7926430},\n\tkeywords = {ATM gene, CNV, HCS, SOPHiA DDM, gallbladder cancer, germline mutations, hereditary cancer predisposition, hereditary cancer syndromes, next-generation sequencing},\n}\n\n

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\n \n\n \n \n \n \n \n \n Automated Capture-Based NGS Workflow: One Thousand Patients Experience in a Clinical Routine Framework.\n \n \n \n \n\n\n \n Tenedini, E.; Celestini, F.; Iapicca, P.; Marino, M.; Castellano, S.; Artuso, L.; Biagiarelli, F.; Cortesi, L.; Toss, A.; Barbieri, E.; Roncucci, L.; Pedroni, M.; Manfredini, R.; Luppi, M.; Trenti, T.; and Tagliafico, E.\n\n\n \n\n\n\n . March 2021.\n Publisher: Preprints\n\n\n\n
\n\n\n\n \n \n $\"Automated$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 4 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{tenedini_automated_2021,\n\ttitle = {Automated {Capture}-{Based} {NGS} {Workflow}: {One} {Thousand} {Patients} {Experience} in a {Clinical} {Routine} {Framework}},\n\tshorttitle = {Automated {Capture}-{Based} {NGS} {Workflow}},\n\turl = {https://www.preprints.org/manuscript/202103.0103/v1},\n\tdoi = {10.20944/preprints202103.0103.v1},\n\tabstract = {(1) Background: the NGS based mutational study of hereditary cancer genes is crucial to design tailored prevention strategies in subjects with different hereditary cancer risk. The ease of amplicon-based NGS library construction protocols contrasts with the greater uniformity of enrichment provided by capture-based protocols and so with greater chances for detecting larger genomic rearrangements and copy-number variations. Capture-based protocols, however, are characterized by a higher level of complexity of sample handling, extremely susceptible to human bias. Robotics platforms may definitely help dealing with these limits, reducing hands-on time, limiting random errors and guaranteeing process standardization. (2) Methods: We implemented and validated the complete automation of the SOPHiA GENETICS\\&rsquo; CE-IVD Hereditary Cancer Solution\\&trade; (HCS) libraries preparation workflow on the Hamilton\\&rsquo;s STARlet platform. (3) Results: We demonstrate that this automated workflow, used for more than 1000 samples achieved the same performances of manual setup in terms of coverages and reads uniformity, with extremely lower variability of reads mapping rate onto the regions of interest. (4) Conclusions: This automated solution offers same reliable and affordable NGS data, but with the essential advantages of a flexible, automated and integrated framework, minimizing possible human errors and depicting a laboratory\\&rsquo;s walk-away scenario.},\n\tlanguage = {en},\n\turldate = {2021-03-10},\n\tauthor = {Tenedini, Elena and Celestini, Fabio and Iapicca, Pierluigi and Marino, Marco and Castellano, Sara and Artuso, Lucia and Biagiarelli, Fiammetta and Cortesi, Laura and Toss, Angela and Barbieri, Elena and Roncucci, Luca and Pedroni, Monica and Manfredini, Rossella and Luppi, Mario and Trenti, Tommaso and Tagliafico, Enrico},\n\tmonth = mar,\n\tyear = {2021},\n\tnote = {Publisher: Preprints},\n\tkeywords = {HCS, Hereditary Disorders, SOPHiA DDM, hereditary cancer syndromes},\n}\n\n

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\n \n\n \n \n \n \n \n \n Prenatal Identification of a Novel Mutation in the MCPH1 Gene Associated with Autosomal Recessive Primary Microcephaly (MCPH) using Next Generation Sequencing (NGS).\n \n \n \n \n\n\n \n Papoulidis, I.; Eleftheriades, M.; Manolakos, E.; Liapi, S. M.; Konstantinidou, A.; Papamichail, M.; Papadipoulos, V.; Garas, A.; Sotiriou, S.; Papastefanou, I.; Daskalakis, G.; and Ristic, A.\n\n\n \n\n\n\n . March 2021.\n Publisher: Preprints\n\n\n\n
\n\n\n\n \n \n $\"Prenatal$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{papoulidis_prenatal_2021,\n\ttitle = {Prenatal {Identification} of a {Novel} {Mutation} in the {MCPH1} {Gene} {Associated} with {Autosomal} {Recessive} {Primary} {Microcephaly} ({MCPH}) using {Next} {Generation} {Sequencing} ({NGS})},\n\turl = {https://www.preprints.org/manuscript/202103.0108/v1},\n\tdoi = {10.20944/preprints202103.0108.v1},\n\tabstract = {MCPH1, otherwise known as the microcephalin gene (*607117) and protein, is a basic regulator of chromosome condensation (BCRT-BRCA1 C-terminus). The Microcephalin protein is made up of three BCRT domains and conserved tandem repeats of interacting phospho-peptide. There is a strong connection between mutations of the MCPH1 and reduced brain growth. Specifically, individuals with such mutations have underdeveloped brains which means smaller size, varying levels of mental retardation, delayed speech and poor language skills, individuals with mild microcephaly and normal intelligence notwithstanding. In this case, a fetus with novel homozygous mutation of the MCPH1 gene ((c.348del)), whose parents were recessive heterozygous for (c.348del), displayed severe microcephaly at 22 weeks of gestation. Due to the effect on splice sites in introns, this mutation causes forming of dysfunctional proteins which lack crucial domains of the C-terminus. Our findings portray an association between the new MCPH1 mutation ((c.348del)) and the clinical features of autosomal recessive primary microcephaly (MCPH) contributing to a broader spectrum related to these pathologies.},\n\tlanguage = {en},\n\turldate = {2021-03-10},\n\tauthor = {Papoulidis, Ioannis and Eleftheriades, Makarios and Manolakos, Emmanouil and Liapi, Simoni Maria and Konstantinidou, Anastasia and Papamichail, Maria and Papadipoulos, Vasileios and Garas, Antonios and Sotiriou, Sotirios and Papastefanou, Ioannis and Daskalakis, Georgios and Ristic, Aleksandar},\n\tmonth = mar,\n\tyear = {2021},\n\tnote = {Publisher: Preprints},\n\tkeywords = {Clinical study, SOPHiA DDM, clinical genomics},\n}\n\n

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\n \n\n \n \n \n \n \n \n APC Splicing Mutations Leading to In-Frame Exon 12 or Exon 13 Skipping Are Rare Events in FAP Pathogenesis and Define the Clinical Outcome.\n \n \n \n \n\n\n \n Disciglio, V.; Forte, G.; Fasano, C.; Sanese, P.; Lepore Signorile, M.; De Marco, K.; Grossi, V.; Cariola, F.; and Simone, C.\n\n\n \n\n\n\n Genes, 12(3): 353. February 2021.\n Number: 3 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"APC$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{disciglio_apc_2021,\n\ttitle = {{APC} {Splicing} {Mutations} {Leading} to {In}-{Frame} {Exon} 12 or {Exon} 13 {Skipping} {Are} {Rare} {Events} in {FAP} {Pathogenesis} and {Define} the {Clinical} {Outcome}},\n\tvolume = {12},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\turl = {https://www.mdpi.com/2073-4425/12/3/353},\n\tdoi = {10.3390/genes12030353},\n\tabstract = {Familial adenomatous polyposis (FAP) is caused by germline mutations in the tumor suppressor gene APC. To date, nearly 2000 APC mutations have been described in FAP, most of which are predicted to result in truncated protein products. Mutations leading to aberrant APC splicing have rarely been reported. Here, we characterized a novel germline heterozygous splice donor site mutation in APC exon 12 (NM\\_000038.5: c.1621\\_1626+7del) leading to exon 12 skipping in an Italian family with the attenuated FAP (AFAP) phenotype. Moreover, we performed a literature meta-analysis of APC splicing mutations. We found that 119 unique APC splicing mutations, including the one described here, have been reported in FAP patients, 69 of which have been characterized at the mRNA level. Among these, only a small proportion (9/69) results in an in-frame protein, with four mutations causing skipping of exon 12 or 13 with loss of armadillo repeat 2 (ARM2) and 3 (ARM3), and five mutations leading to skipping of exon 5, 7, 8, or (partially) 9 with loss of regions not encompassing known functional domains. The APC splicing mutations causing skipping of exon 12 or 13 considered in this study cluster with the AFAP phenotype and reveal a potential molecular mechanism of pathogenesis in FAP disease.},\n\tlanguage = {en},\n\tnumber = {3},\n\turldate = {2021-03-09},\n\tjournal = {Genes},\n\tauthor = {Disciglio, Vittoria and Forte, Giovanna and Fasano, Candida and Sanese, Paola and Lepore Signorile, Martina and De Marco, Katia and Grossi, Valentina and Cariola, Filomena and Simone, Cristiano},\n\tmonth = feb,\n\tyear = {2021},\n\tnote = {Number: 3\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {APC, Alamut, FAP pathogenesis, SOPHiA DDM, exon skipping, familial adenomatous polyposis, splicing},\n\tpages = {353},\n}\n\n

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\n \n\n \n \n \n \n \n Role of 3-D volume growth rate for drug activity evaluation in meningioma clinical trials: the example of the CEVOREM study.\n \n \n \n\n\n \n Graillon, T.; Ferrer, L.; Siffre, J.; Sanson, M.; Peyre, M.; Peyrière, H.; Mougel, G.; Autran, D.; Tabouret, E.; Figarella-Branger, D.; Barlier, A.; Kalamarides, M.; Dufour, H.; Colin, T.; and Chinot, O.\n\n\n \n\n\n\n Neuro-Oncology. February 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{graillon_role_2021,\n\ttitle = {Role of 3-{D} volume growth rate for drug activity evaluation in meningioma clinical trials: the example of the {CEVOREM} study},\n\tissn = {1523-5866},\n\tshorttitle = {Role of 3-{D} volume growth rate for drug activity evaluation in meningioma clinical trials},\n\tdoi = {10.1093/neuonc/noab019},\n\tabstract = {BACKGROUND: We aimed to improve the assessment of the drug activity in meningioma clinical trials based on the study of the 3D volume growth rate (3DVGR) in a series of aggressive meningiomas. We secondarily aimed to correlate 3DVGR study with patient outcome.\nMETHODS: We performed a posthoc analysis based on volume data and 3DVGR extracted from CEVOREM study including 18 patients with 32 recurrent high-grade meningiomas and treated with everolimus and octreotide. The joint latent class model was used to classify tumor 3DVGR under treatment.\nRESULTS: Class 1 includes lesions responding to treatment with decrease in volume in the first 3 months, and then a stabilization thereafter (9.5\\% of tumors) (mean pretreatment 3DVGR=6.13\\%/month; mean under treatment 3DVGR=-18.7\\%/month within 3 first months and -0.14\\%/month after the 3 first months). Class 2 includes lesions considered as stable or with a slight increase in volume under treatment (65.5\\%) (mean pretreatment 3DVGR=6.09\\%/month; under treatment 3DVGR=-0.09\\% within the first 3 months). Class 3 includes lesions without 3DVGR decrease (25\\%) (mean pretreatment 3DVGR=46.9\\%/month; mean under treatment 3DVGR=19.2\\%/month within the first 3 months).Patients with class 3 lesions had a significantly worse progression free survival rate (PFS) than class 1 and 2 ones.\nDISCUSSION: Tumor 3DVGR could be helpful to detect early signal of drugs antitumoral activity or non-activity. This volume response classification could help in the assessment of drug activity in tumors with mostly volume stabilization and rare response as aggressive meningiomas even with a low number of patients in complement to 6 months PFS.},\n\tlanguage = {eng},\n\tjournal = {Neuro-Oncology},\n\tauthor = {Graillon, T. and Ferrer, L. and Siffre, J. and Sanson, M. and Peyre, M. and Peyrière, H. and Mougel, G. and Autran, D. and Tabouret, E. and Figarella-Branger, D. and Barlier, A. and Kalamarides, M. and Dufour, H. and Colin, T. and Chinot, O.},\n\tmonth = feb,\n\tyear = {2021},\n\tpmid = {33556177},\n\tkeywords = {Radiomics, clinical trial, drug activity, meningioma, outcome, tumor growth rate},\n}\n\n

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\n \n\n \n \n \n \n \n Collagen VI-Related Myopathy Caused by Compound Heterozygous Mutations of COL6A3 in a Consanguineous Kurdish Family.\n \n \n \n\n\n \n Mihaylova, V.; Chablais, F.; Bremer, J.; Guggenberger, R.; Rushing, E. J.; Bethge, T.; Spiegel, R.; and Jung, H.\n\n\n \n\n\n\n Journal of Clinical Neuromuscular Disease, 22(3): 173–179. March 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{mihaylova_collagen_2021,\n\ttitle = {Collagen {VI}-{Related} {Myopathy} {Caused} by {Compound} {Heterozygous} {Mutations} of {COL6A3} in a {Consanguineous} {Kurdish} {Family}},\n\tvolume = {22},\n\tissn = {1537-1611},\n\tdoi = {10.1097/CND.0000000000000320},\n\tabstract = {ABSTRACT: Collagen VI-related myopathies are caused by mutations of COL6A1, COL6A2, and COL6A3 and present with a wide phenotypic spectrum ranging from severe Ulrich congenital muscular dystrophy to mild Bethlem myopathy. Here, we report a consanguineous Kurdish family with 3 siblings affected by autosomal-recessive Bethlem myopathy caused by compound heterozygous mutations of COL6A3. We found the previously described missense mutation c.7447A {\\textgreater} G/p.(Lys2483Glu) and a novel large deletion encompassing the exon 1-39 of the COL6A3 gene. Apart from the classical clinical symptoms, all patients had keratoconus, which expands the phenotype of the collagen VI-related myopathies.},\n\tlanguage = {eng},\n\tnumber = {3},\n\tjournal = {Journal of Clinical Neuromuscular Disease},\n\tauthor = {Mihaylova, Violeta and Chablais, Fabian and Bremer, Juliane and Guggenberger, Roman and Rushing, Elisabeth J. and Bethge, Tobias and Spiegel, Roland and Jung, Hans-Heinrich},\n\tmonth = mar,\n\tyear = {2021},\n\tpmid = {33596003},\n\tpages = {173--179},\n}\n\n

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\n \n\n \n \n \n \n \n Artificial Intelligence in Clinical Care.\n \n \n \n\n\n \n Girosi, F.; Mann, S.; and Kareddy, V.\n\n\n \n\n\n\n ,171. February 2021.\n \n\n\n\n
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@article{girosi_artificial_2021,\n\ttitle = {Artificial {Intelligence} in {Clinical} {Care}},\n\tlanguage = {en},\n\tauthor = {Girosi, Federico and Mann, Sean and Kareddy, Vishnupriya},\n\tmonth = feb,\n\tyear = {2021},\n\tkeywords = {Alamut, SOPHiA DDM},\n\tpages = {171},\n}\n\n

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\n \n\n \n \n \n \n \n KCNE2 gene mutation and Brugada syndrome.\n \n \n \n\n\n \n Liatakis, I.; Pantou, M. P.; Gourzi, P.; Bazoukis, G.; Mililis, P.; Saplaouras, A.; Vlachos, K.; Prappa, E.; Degiannis, D.; Efremidis, M.; and Letsas, K. P.\n\n\n \n\n\n\n Journal of Electrocardiology, 65: 143–145. February 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{liatakis_kcne2_2021,\n\ttitle = {{KCNE2} gene mutation and {Brugada} syndrome},\n\tvolume = {65},\n\tissn = {1532-8430},\n\tdoi = {10.1016/j.jelectrocard.2021.01.022},\n\tabstract = {KCNE2 gene mutations have been associated with atrial fibrillation, long QT syndrome, Brugada syndrome and unexplained sudden cardiac death. Herein, we describe a case of Brugada syndrome carrying an heterozygous variant in the KCNE2 gene [NM\\_172201.2:c.161 T {\\textgreater} C, p.(Met54Thr, M54T)]. Gain of function of the Ito current possibly explains the Brugada ECG phenotype in this case.},\n\tlanguage = {eng},\n\tjournal = {Journal of Electrocardiology},\n\tauthor = {Liatakis, Ioannis and Pantou, Malena P. and Gourzi, Polyxeni and Bazoukis, George and Mililis, Panagiotis and Saplaouras, Athanasios and Vlachos, Konstantinos and Prappa, Efstathia and Degiannis, Dimitrios and Efremidis, Michael and Letsas, Konstantinos P.},\n\tmonth = feb,\n\tyear = {2021},\n\tpmid = {33626434},\n\tkeywords = {Brugada syndrome, KCNE2 gene, Mutation},\n\tpages = {143--145},\n}\n\n

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\n \n\n \n \n \n \n \n SLC25A38 Congenital Sideroblastic Anemia: Phenotypes and genotypes of 31 individuals from 24 families, including 11 novel mutations, and a review of the literature.\n \n \n \n\n\n \n Heeney, M.; Berhe, S.; Campagna, D.; Oved, J.; Kurre, P.; Shaw, P.; Teo, J.; Shanap, M.; Hassab, H.; Glader, B.; Shah, S.; Yoshimi, A.; Ameri, A.; Antin, J.; Boudreaux, J.; Briones, M.; Dickerson, K.; Fernandez, C.; Farah, R.; and Fleming, M.\n\n\n \n\n\n\n February 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@book{heeney_slc25a38_2021,\n\ttitle = {{SLC25A38} {Congenital} {Sideroblastic} {Anemia}: {Phenotypes} and genotypes of 31 individuals from 24 families, including 11 novel mutations, and a review of the literature},\n\tshorttitle = {{SLC25A38} {Congenital} {Sideroblastic} {Anemia}},\n\tabstract = {The congenital sideroblastic anemias (CSAs) are a heterogeneous group of inherited disorders of erythropoiesis characterized by pathologic deposits of iron in the mitochondria of developing erythroblasts. Mutations in the mitochondrial glycine carrier SLC25A38 cause the most common recessive form of CSA. Nonetheless, the disease is still rare, there being fewer than 70 reported families. Here we describe the clinical phenotype and genotypes of 31 individuals from 24 families, including 11 novel mutations. We also review the spectrum of reported mutations and genotypes associated with the disease, describe the unique localization of missense mutations in transmembrane domains and account for the reoccurrence of several alleles in different populations.},\n\tauthor = {Heeney, Matthew and Berhe, Simon and Campagna, Dean and Oved, Joseph and Kurre, Peter and Shaw, Peter and Teo, Juliana and Shanap, Mayada and Hassab, Hoda and Glader, Bertil and Shah, Sanjay and Yoshimi, Ayami and Ameri, Afshin and Antin, Joseph and Boudreaux, Jeanne and Briones, Michael and Dickerson, Kathryn and Fernandez, Conrad and Farah, Roula and Fleming, Mark},\n\tmonth = feb,\n\tyear = {2021},\n\tdoi = {10.22541/au.161244027.72766594/v1},\n\tkeywords = {Alamut},\n}\n\n

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\n \n\n \n \n \n \n \n \n Different Phenotypes in Pseudodominant Inherited Retinal Dystrophies.\n \n \n \n \n\n\n \n Habibi, I.; Falfoul, Y.; Tran, H. V.; El Matri, K.; Chebil, A.; El Matri, L.; and Schorderet, D. F.\n\n\n \n\n\n\n Frontiers in Cell and Developmental Biology, 9. February 2021.\n Publisher: Frontiers\n\n\n\n
\n\n\n\n \n \n $\"Different$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{habibi_different_2021,\n\ttitle = {Different {Phenotypes} in {Pseudodominant} {Inherited} {Retinal} {Dystrophies}},\n\tvolume = {9},\n\tissn = {2296-634X},\n\turl = {https://www.frontiersin.org/articles/10.3389/fcell.2021.625560/full},\n\tdoi = {10.3389/fcell.2021.625560},\n\tabstract = {Retinal dystrophies (RD) are a group of Mendelian disorders caused by rare genetic variations leading to blindness. A pathogenic variant may manifest in both dominant or recessive mode and clinical and genetic heterogeneity makes it difficult to establish a precise diagnosis. In this study, families with autosomal dominant RD in successive generations were identified, and we aimed to determine the disease’s molecular origin in these consanguineous families. Whole exome sequencing was performed in the index patient of each family. The aim was to determine whether these cases truly represented examples of dominantly inherited RD, or whether another mode of inheritance might be applicable. Six potentially pathogenic variants in 4 genes were identified in 4 families. In index patient with enhanced S-cone syndrome in F1, we identified a new digenetic combination: a heterozygous variant p.[G51A];[=] in RHO and a homozygous pathogenic variant p.[R311Q];[R311Q] in NR2E3. Helicoid subretinal fibrosis associated with recessive NR2E3 variant p.[R311Q];[R311Q] was identified in F2. A new frameshift variant c.[105delG];[105delG] in RDH12 was found in F3 with cone-rod dystrophy. In F4, the compound heterozygous variants p.[R964*];[W758*] were observed in IMPG2 with a retinitis pigmentosa (RP) phenotype. We showed that both affected parents and the offspring, were homozygous for the same variants in all 4 families. Our results provide evidence that in consanguineous families, autosomal recessive can be transmitted as pseudodominant inheritance in RD patients, and further extend our knowledge of pathogenic variants in RD genes.},\n\tlanguage = {English},\n\turldate = {2021-02-25},\n\tjournal = {Frontiers in Cell and Developmental Biology},\n\tauthor = {Habibi, Imen and Falfoul, Yosra and Tran, Hoai Viet and El Matri, Khaled and Chebil, Ahmed and El Matri, Leila and Schorderet, Daniel F.},\n\tmonth = feb,\n\tyear = {2021},\n\tnote = {Publisher: Frontiers},\n\tkeywords = {CES, CES v2, Pathogenic variants, Pseudodominant inheritance, Retinal Dystrophies, Retinitis Pigmentosa, whole exome sequencing},\n}\n\n

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\n \n\n \n \n \n \n \n \n Reproductive Isolation from Incompatible Hybrid Mitotic Exit Networks (HyMEN).\n \n \n \n \n\n\n \n Hutter, P.\n\n\n \n\n\n\n Enliven: J Genet Mol Cell Biol. February 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"Reproductive$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{hutter_reproductive_2021,\n\ttitle = {Reproductive {Isolation} from {Incompatible} {Hybrid} {Mitotic} {Exit} {Networks} ({HyMEN})},\n\turl = {http://www.enlivenarchive.org/data/reproductive-isolation-from-incompatible-ihiybrid-imiitotic-ieixit-inietworks-ihymeni-0.html},\n\tabstract = {At the end of mitosis the Mitotic Exit Network (MEN) pathway triggers complex tasks which mainly include the spindle disassembly and the nuclear envelopes assembly. In the course of telophase, which often lasts less than an hour and corresponds to only about 2\\% of the entire cell cycle’s duration,spatial and temporal cues are integrated to ensure that cytokinesis occurs after the genome has partitioned between mother and daughter cells. From the end of anaphase through telophase, sequential components of a Ras-like GTPase signaling pathway are controlled by a set of different spatial and temporal signals. Successful propagation of these signals through multi-step transduction requires a remarkably complex coordination. By considering that cells lacking proper MEN function fail to exit from mitosis, I argue that in a hybrid genome impaired coordination between two diverged MENs is prone to result in critical mitotic defects, from late anaphase through telophase. The so-called HyMEN model of hybrid incompatibility depicted here can be regarded as an extension of the Bateson-Dobzhansky-Muller model of speciation, centered on the MEN.},\n\tjournal = {Enliven: J Genet Mol Cell Biol},\n\tauthor = {Hutter, Pierre},\n\tmonth = feb,\n\tyear = {2021},\n}\n\n

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\n \n\n \n \n \n \n \n Characterization of New ATM Deletion Associated with Hereditary Breast Cancer.\n \n \n \n\n\n \n Parenti, S.; Rabacchi, C.; Marino, M.; Tenedini, E.; Artuso, L.; Castellano, S.; Carretta, C.; Mallia, S.; Cortesi, L.; Toss, A.; Barbieri, E.; Manfredini, R.; Luppi, M.; Trenti, T.; and Tagliafico, E.\n\n\n \n\n\n\n Genes, 12(2). January 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{parenti_characterization_2021,\n\ttitle = {Characterization of {New} {ATM} {Deletion} {Associated} with {Hereditary} {Breast} {Cancer}},\n\tvolume = {12},\n\tissn = {2073-4425},\n\tdoi = {10.3390/genes12020136},\n\tabstract = {Next-generation sequencing (NGS)-based cancer risk screening with multigene panels has become the most successful method for programming cancer prevention strategies. ATM germ-line heterozygosity has been described to increase tumor susceptibility. In particular, families carrying heterozygous germ-line variants of ATM gene have a 5- to 9-fold risk of developing breast cancer. Recent studies identified ATM as the second most mutated gene after CHEK2 in BRCA-negative patients. Nowadays, more than 170 missense variants and several truncating mutations have been identified in ATM gene. Here, we present the molecular characterization of a new ATM deletion, identified thanks to the CNV algorithm implemented in the NGS analysis pipeline. An automated workflow implementing the SOPHiA Genetics' Hereditary Cancer Solution (HCS) protocol was used to generate NGS libraries that were sequenced on Illumina MiSeq Platform. NGS data analysis allowed us to identify a new inactivating deletion of exons 19-27 of ATM gene. The deletion was characterized both at the DNA and RNA level.},\n\tlanguage = {eng},\n\tnumber = {2},\n\tjournal = {Genes},\n\tauthor = {Parenti, Sandra and Rabacchi, Claudio and Marino, Marco and Tenedini, Elena and Artuso, Lucia and Castellano, Sara and Carretta, Chiara and Mallia, Selene and Cortesi, Laura and Toss, Angela and Barbieri, Elena and Manfredini, Rossella and Luppi, Mario and Trenti, Tommaso and Tagliafico, Enrico},\n\tmonth = jan,\n\tyear = {2021},\n\tpmid = {33494414},\n\tkeywords = {ATM, CNV, HCS, SOPHiA DDM, breast cancer, clinical genomics, hereditary cancer syndromes, homologous recombination repair, molecular diagnostics, next-generation sequencing},\n}\n\n

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\n \n\n \n \n \n \n \n \n RPE65-related retinal dystrophy: mutational and phenotypic spectrum in 45 affected patients.\n \n \n \n \n\n\n \n Lopez-Rodriguez, R.; Lantero, E.; Blanco-Kelly, F.; Avila-Fernandez, A.; Merida, I. M.; Pozo-Valero, M. d.; Perea-Romero, I.; Zurita, O.; Jiménez-Rolando, B.; Swafiri, S. T.; Riveiro-Alvarez, R.; Trujillo-Tiebas, M. J.; Salas, E. C.; García-Sandoval, B.; Corton, M.; and Ayuso, C.\n\n\n \n\n\n\n medRxiv,2021.01.19.21249492. January 2021.\n Publisher: Cold Spring Harbor Laboratory Press\n\n\n\n
\n\n\n\n \n \n $\"RPE65-related$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{lopez-rodriguez_rpe65-related_2021,\n\ttitle = {{RPE65}-related retinal dystrophy: mutational and phenotypic spectrum in 45 affected patients},\n\tcopyright = {© 2021, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution-NoDerivs 4.0 International), CC BY-ND 4.0, as described at http://creativecommons.org/licenses/by-nd/4.0/},\n\tshorttitle = {{RPE65}-related retinal dystrophy},\n\turl = {https://www.medrxiv.org/content/10.1101/2021.01.19.21249492v2},\n\tdoi = {10.1101/2021.01.19.21249492},\n\tabstract = {{\\textless}p{\\textgreater}Background: Biallelic pathogenic RPE65 variants are related to a spectrum of clinically overlapping inherited retinal dystrophies (IRD). Most affected individuals show a severe progression, with 50\\% of patients legally blind by 20 years of age. A better knowledge of the mutational spectrum and the phenotype−genotype correlation in RPE65−related IRD is needed. Methods: Forty−five affected subjects from 27 unrelated families with a clinical diagnosis of RPE65−related IRD were included. Clinical evaluation consisted on self−reported ophthalmological history and objective ophthalmological examination. Patients9 genotype was classified accordingly to variant class (truncating or missense) or to variant location at different protein domains. Main phenotypic outcome was age at onset (AAO) of the symptomatic disease and a Kaplan−Meier analysis of disease symptom event−free survival was performed. Results: Twenty−nine different RPE65 variants were identified in our cohort, 7 of them novel. Most frequent variants were p.(Ile98Hisfs*26), p.(Pro111Ser) and p.(Gly187Glu) accounting for the 24\\% of the detected alleles. Patients carrying two missense alleles showed a later disease onset than those with 1 or 2 truncating variants (Log Rank test p\\&lt;0.05). While the 60\\% of patients carrying a missense/missense genotype presented symptoms before or at the first year of life, almost all patients with at least 1 truncating allele (91\\%) had an AAO ≤1 year (p\\&lt;0.05). Conclusion: Our findings suggest an association between the type of the RPE65 carried variant and the AAO. Thus, our results provide useful data on RPE65-associated IRD phenotypes which may help to improve clinical and therapeutic management of these patients.{\\textless}/p{\\textgreater}},\n\tlanguage = {en},\n\turldate = {2021-02-08},\n\tjournal = {medRxiv},\n\tauthor = {Lopez-Rodriguez, R. and Lantero, E. and Blanco-Kelly, F. and Avila-Fernandez, A. and Merida, I. Martin and Pozo-Valero, M. del and Perea-Romero, I. and Zurita, O. and Jiménez-Rolando, B. and Swafiri, S. T. and Riveiro-Alvarez, R. and Trujillo-Tiebas, M. J. and Salas, E. Carreño and García-Sandoval, B. and Corton, M. and Ayuso, C.},\n\tmonth = jan,\n\tyear = {2021},\n\tnote = {Publisher: Cold Spring Harbor Laboratory Press},\n\tkeywords = {TruSight},\n\tpages = {2021.01.19.21249492},\n}\n\n

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\n \n\n \n \n \n \n \n \n Stepwise Reversal of Immune Dysregulation Due to STAT1 Gain-of-Function Mutation Following Ruxolitinib Bridge Therapy and Transplantation.\n \n \n \n \n\n\n \n B, K.; N, K.; Ns, Y.; Lm, C.; B, G.; A, A.; Sb, E.; G, O.; A, O.; E, K.; Ta, C.; M, G.; and S, B.\n\n\n \n\n\n\n January 2021.\n ISSN: 1573-2592 Publisher: J Clin Immunol\n\n\n\n
\n\n\n\n \n \n $\"Stepwise$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@misc{b_stepwise_2021,\n\ttitle = {Stepwise {Reversal} of {Immune} {Dysregulation} {Due} to {STAT1} {Gain}-of-{Function} {Mutation} {Following} {Ruxolitinib} {Bridge} {Therapy} and {Transplantation}},\n\turl = {https://pubmed.ncbi.nlm.nih.gov/33475942/},\n\tabstract = {Our findings suggest that improved disease management and immune dysregulatory profile can be achieved with ruxolitinib treatment before transplantation and this would be beneficial to reduce the risk of adverse outcome of HSCT.},\n\tlanguage = {en},\n\turldate = {2021-02-08},\n\tjournal = {Journal of clinical immunology},\n\tauthor = {B, Kayaoglu and N, Kasap and Ns, Yilmaz and Lm, Charbonnier and B, Geckin and A, Akcay and Sb, Eltan and G, Ozturk and A, Ozen and E, Karakoc-Aydiner and Ta, Chatila and M, Gursel and S, Baris},\n\tmonth = jan,\n\tyear = {2021},\n\tpmid = {33475942},\n\tdoi = {10.1007/s10875-020-00943-y},\n\tnote = {ISSN: 1573-2592\nPublisher: J Clin Immunol},\n\tkeywords = {CES, Clinical Exome, SOPHiA DDM},\n}\n\n

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\n \n\n \n \n \n \n \n \n Management of patients with severe acute respiratory failure due to SARSCoV-2 pneumonia with non-invasive ventilatory support outside Intensive Care Unit.\n \n \n \n \n\n\n \n T, D. d. T.; M, G. M.; P, B.; G, G.; G, F.; G, R.; F, C.; M, V.; M, B.; A, P.; C, B.; A, B.; A, N.; and P, S.\n\n\n \n\n\n\n January 2021.\n ISSN: 1827-1669 Publisher: Minerva Med\n\n\n\n
\n\n\n\n \n \n $\"Management$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@misc{t_management_2021,\n\ttitle = {Management of patients with severe acute respiratory failure due to {SARSCoV}-2 pneumonia with non-invasive ventilatory support outside {Intensive} {Care} {Unit}},\n\turl = {https://pubmed.ncbi.nlm.nih.gov/33464224/},\n\tabstract = {NIVS is a safe and effective strategy in the treatment of severe ARF due to COVID 19 related pneumonia, that reduces mortality and length of hospital stay in the carefully selected patient.},\n\tlanguage = {en},\n\turldate = {2021-02-08},\n\tjournal = {Minerva medica},\n\tauthor = {T, Diaz de Teran and M, Gonzales Martinez and P, Banfi and G, Garuti and G, Ferraioli and G, Russo and F, Casu and M, Vivarelli and M, Bonfiglio and A, Perazzo and C, Barlascini and A, Bauleo and A, Nicolini and P, Solidoro},\n\tmonth = jan,\n\tyear = {2021},\n\tpmid = {33464224},\n\tdoi = {10.23736/S0026-4806.21.07134-2},\n\tnote = {ISSN: 1827-1669\nPublisher: Minerva Med},\n\tkeywords = {SARSCoV-2},\n}\n\n

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\n \n\n \n \n \n \n \n \n Whole Exome Sequencing in Coloboma/Microphthalmia: Identification of Novel and Recurrent Variants in Seven Genes.\n \n \n \n \n\n\n \n Haug, P.; Koller, S.; Maggi, J.; Lang, E.; Feil, S.; Wlodarczyk, A.; Bähr, L.; Steindl, K.; Rohrbach, M.; Gerth-Kahlert, C.; and Berger, W.\n\n\n \n\n\n\n Genes, 12(1): 65. January 2021.\n Number: 1 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Whole$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{haug_whole_2021,\n\ttitle = {Whole {Exome} {Sequencing} in {Coloboma}/{Microphthalmia}: {Identification} of {Novel} and {Recurrent} {Variants} in {Seven} {Genes}},\n\tvolume = {12},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tshorttitle = {Whole {Exome} {Sequencing} in {Coloboma}/{Microphthalmia}},\n\turl = {https://www.mdpi.com/2073-4425/12/1/65},\n\tdoi = {10.3390/genes12010065},\n\tabstract = {Coloboma and microphthalmia (C/M) are related congenital eye malformations, which can cause significant visual impairment. Molecular diagnosis is challenging as the genes associated to date with C/M account for only a small percentage of cases. Overall, the genetic cause remains unknown in up to 80\\% of patients. High throughput DNA sequencing technologies, including whole-exome sequencing (WES), are therefore a useful and efficient tool for genetic screening and identification of new mutations and novel genes in C/M. In this study, we analyzed the DNA of 19 patients with C/M from 15 unrelated families using singleton WES and data analysis for 307 genes of interest. We identified seven novel and one recurrent potentially disease-causing variants in CRIM1, CHD7, FAT1, PTCH1, PUF60, BRPF1, and TGFB2 in 47\\% of our families, three of which occurred de novo. The detection rate in patients with ocular and extraocular manifestations (67\\%) was higher than in patients with an isolated ocular phenotype (46\\%). Our study highlights the significant genetic heterogeneity in C/M cohorts and emphasizes the diagnostic power of WES for the screening of patients and families with C/M.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2021-01-12},\n\tjournal = {Genes},\n\tauthor = {Haug, Patricia and Koller, Samuel and Maggi, Jordi and Lang, Elena and Feil, Silke and Wlodarczyk, Agnès and Bähr, Luzy and Steindl, Katharina and Rohrbach, Marianne and Gerth-Kahlert, Christina and Berger, Wolfgang},\n\tmonth = jan,\n\tyear = {2021},\n\tnote = {Number: 1\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Alamut, Exome, MAC, SOPHiA DDM, anterior segment dysgenesis, coloboma, exome sequencing, genetic screening, microphthalmia, ocular development, whole-exome sequencing},\n\tpages = {65},\n}\n\n

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\n \n\n \n \n \n \n \n Performance of In Silico Prediction Tools for the Detection of Germline Copy Number Variations in Cancer Predisposition Genes in 4208 Female Index Patients with Familial Breast and Ovarian Cancer.\n \n \n \n\n\n \n Lepkes, L.; Kayali, M.; Blümcke, B.; Weber, J.; Suszynska, M.; Schmidt, S.; Borde, J.; Klonowska, K.; Wappenschmidt, B.; Hauke, J.; Kozlowski, P.; Schmutzler, R. K.; Hahnen, E.; and Ernst, C.\n\n\n \n\n\n\n Cancers, 13(1). January 2021.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 4 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{lepkes_performance_2021,\n\ttitle = {Performance of {In} {Silico} {Prediction} {Tools} for the {Detection} of {Germline} {Copy} {Number} {Variations} in {Cancer} {Predisposition} {Genes} in 4208 {Female} {Index} {Patients} with {Familial} {Breast} and {Ovarian} {Cancer}},\n\tvolume = {13},\n\tissn = {2072-6694},\n\tdoi = {10.3390/cancers13010118},\n\tabstract = {The identification of germline copy number variants (CNVs) by targeted next-generation sequencing (NGS) frequently relies on in silico CNV prediction tools with unknown sensitivities. We investigated the performances of four in silico CNV prediction tools, including one commercial (Sophia Genetics DDM) and three non-commercial tools (ExomeDepth, GATK gCNV, panelcn.MOPS) in 17 cancer predisposition genes in 4208 female index patients with familial breast and/or ovarian cancer (BC/OC). CNV predictions were verified via multiplex ligation-dependent probe amplification. We identified 77 CNVs in 76 out of 4208 patients (1.81\\%); 33 CNVs were identified in genes other than BRCA1/2, mostly in ATM, CHEK2, and RAD51C and less frequently in BARD1, MLH1, MSH2, PALB2, PMS2, RAD51D, and TP53. The Sophia Genetics DDM software showed the highest sensitivity; six CNVs were missed by at least one of the non-commercial tools. The positive predictive values ranged from 5.9\\% (74/1249) for panelcn.MOPS to 79.1\\% (72/91) for ExomeDepth. Verification of in silico predicted CNVs is required due to high frequencies of false positive predictions, particularly affecting target regions at the extremes of the GC content or target length distributions. CNV detection should not be restricted to BRCA1/2 due to the relevant proportion of CNVs in further BC/OC predisposition genes.},\n\tlanguage = {eng},\n\tnumber = {1},\n\tjournal = {Cancers},\n\tauthor = {Lepkes, Louisa and Kayali, Mohamad and Blümcke, Britta and Weber, Jonas and Suszynska, Malwina and Schmidt, Sandra and Borde, Julika and Klonowska, Katarzyna and Wappenschmidt, Barbara and Hauke, Jan and Kozlowski, Piotr and Schmutzler, Rita K. and Hahnen, Eric and Ernst, Corinna},\n\tmonth = jan,\n\tyear = {2021},\n\tpmid = {33401422},\n\tkeywords = {Benchmark, CNV, HBOC, SOPHiA DDM, breast/ovarian cancer susceptibility genes, multigene panel sequencing},\n}\n\n

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\n \n\n \n \n \n \n \n \n A new LRP6 variant and Camurati-Engelmann-like disease.\n \n \n \n \n\n\n \n Pickering, M.; Ltaief-Boudrigua, A.; Feurer, E.; Collet, C.; and Chapurlat, R.\n\n\n \n\n\n\n Bone, 143: 115706. January 2021.\n \n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{pickering_new_2021,\n\ttitle = {A new {LRP6} variant and {Camurati}-{Engelmann}-like disease},\n\tvolume = {143},\n\tissn = {8756-3282},\n\turl = {http://www.sciencedirect.com/science/article/pii/S8756328220304865},\n\tdoi = {10.1016/j.bone.2020.115706},\n\tabstract = {Introduction\nCamurati-Engelmann disease is a rare autosomal dominant bone dysplasia belonging to the group of craniotubular hyperostoses. Genetic analysis classically shows mutation on TGFβ1 gene.\nCase report\nA young woman was hospitalized with intense pain in lower limbs, associated to radiographic hyperostosis and sclerosis of the long bones.\nResults\nMutation on LRP6 has recently been associated to high bone mass. In this case report, a rare missense variant on LRP6 gene was associated to radiographic features of Camurati-Engelmann.\nConclusions\nMore studies should be conducted to assess the pathological role of this variant in Camurati-Engelmann-like disease.},\n\tlanguage = {en},\n\turldate = {2020-11-30},\n\tjournal = {Bone},\n\tauthor = {Pickering, Marie-Eva and Ltaief-Boudrigua, Aicha and Feurer, Elodie and Collet, Corinne and Chapurlat, Roland},\n\tmonth = jan,\n\tyear = {2021},\n\tkeywords = {Genetics, Osteosclerosis, SOPHiA DDM, lrp6},\n\tpages = {115706},\n}\n\n

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\n \n 2020\n \n \n (87)\n \n \n

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\n \n\n \n \n \n \n \n Mutational spectrum and classification of novel mutations in patients with metastatic gastrointestinal stromal tumours.\n \n \n \n\n\n \n Bombac, A.; Zakotnik, B.; Bucic, M.; Setrajcic Dragos, V.; Gazic, B.; Stegel, V.; Klancar, G.; and Novakovic, S.\n\n\n \n\n\n\n International Journal of Oncology, 56(6): 1468–1478. March 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{bombac_mutational_2020,\n\ttitle = {Mutational spectrum and classification of novel mutations in patients with metastatic gastrointestinal stromal tumours},\n\tvolume = {56},\n\tissn = {1791-2423},\n\tdoi = {10.3892/ijo.2020.5028},\n\tabstract = {In total, {\\textasciitilde}85\\% of malignant gastrointestinal stromal tumours (GISTs) harbour activating mutations in one of the genes KIT or PDGFRA, while 10‑15\\% of all GISTs have no detectable KIT or PDGFRA mutations, but could have alterations in genes of the succinate dehydrogenase complex or in BRAF, PIK3CA or rarely RAS family genes. The clinical benefit of tyrosine kinase inhibitors, such as imatinib, depends on the GIST genotype, therefore molecular characterization of GIST has a crucial role in overall management of GIST. The aim of the present study was to molecularly characterize a cohort of 70 patients with metastatic GISTs from the Slovenian Cancer Registry (National Cancer Registry) treated between January 2002 and December 2011. Exons 9, 11, 13 and 17 of the KIT gene and exons 12, 14 and 18 of the PDGFRA gene were analysed by direct Sanger sequencing. All KIT/PDGFRA wild‑type GISTs were tested for the presence of mutations in hot spot regions of KRAS, NRAS, BRAF, PIK3CA and AKT1 genes. Novel variants were characterized and classified using Cancer Genome Interpreter and according to The American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines. In total, 60 (85.7\\%) patients had mutations in KIT and 2 (2.9\\%) in PDGFRA. Whereas, 8 (11.4\\%) patients with GIST had no mutation in either of the analysed genes. The majority of GIST cases (n=52) had a mutation in KIT exon 11, where 40 different mutations were detected. Eight of the variants were novel: c.1652\\_1672del, c.1653\\_1660delinsAA, c.1665\\_1672delinsCC, c.1668\\_1686del, c.1676\\_1720del, c.1715\\_1756dup, c.1721\\_1765dup, and c.1722\\_1766dup. Mutation frequencies of KIT and PDGFRA genes observed in Slovenian patients are comparable with those in other European populations. In the present group of patients analysed, the most frequently mutated region was exon 11 in the KIT gene, responsible for coding juxtamembrane domain of KIT protein. In this region, eight novel mutations were identified and classified as likely pathogenic driver variants. In addition, the present study identified 6 patients with secondary KIT mutation and 1 patient with double mutant GIST, who had two different mutations in PDGFRA exon 14.},\n\tlanguage = {eng},\n\tnumber = {6},\n\tjournal = {International Journal of Oncology},\n\tauthor = {Bombac, Alenka and Zakotnik, Branko and Bucic, Marina and Setrajcic Dragos, Vita and Gazic, Barbara and Stegel, Vida and Klancar, Gasper and Novakovic, Srdjan},\n\tmonth = mar,\n\tyear = {2020},\n\tpmid = {32236636},\n\tpmcid = {PMC7170035},\n\tkeywords = {Gastrointestinal stromal tumour},\n\tpages = {1468--1478},\n}\n\n

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\n In total, ~85% of malignant gastrointestinal stromal tumours (GISTs) harbour activating mutations in one of the genes KIT or PDGFRA, while 10‑15% of all GISTs have no detectable KIT or PDGFRA mutations, but could have alterations in genes of the succinate dehydrogenase complex or in BRAF, PIK3CA or rarely RAS family genes. The clinical benefit of tyrosine kinase inhibitors, such as imatinib, depends on the GIST genotype, therefore molecular characterization of GIST has a crucial role in overall management of GIST. The aim of the present study was to molecularly characterize a cohort of 70 patients with metastatic GISTs from the Slovenian Cancer Registry (National Cancer Registry) treated between January 2002 and December 2011. Exons 9, 11, 13 and 17 of the KIT gene and exons 12, 14 and 18 of the PDGFRA gene were analysed by direct Sanger sequencing. All KIT/PDGFRA wild‑type GISTs were tested for the presence of mutations in hot spot regions of KRAS, NRAS, BRAF, PIK3CA and AKT1 genes. Novel variants were characterized and classified using Cancer Genome Interpreter and according to The American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines. In total, 60 (85.7%) patients had mutations in KIT and 2 (2.9%) in PDGFRA. Whereas, 8 (11.4%) patients with GIST had no mutation in either of the analysed genes. The majority of GIST cases (n=52) had a mutation in KIT exon 11, where 40 different mutations were detected. Eight of the variants were novel: c.1652_1672del, c.1653_1660delinsAA, c.1665_1672delinsCC, c.1668_1686del, c.1676_1720del, c.1715_1756dup, c.1721_1765dup, and c.1722_1766dup. Mutation frequencies of KIT and PDGFRA genes observed in Slovenian patients are comparable with those in other European populations. In the present group of patients analysed, the most frequently mutated region was exon 11 in the KIT gene, responsible for coding juxtamembrane domain of KIT protein. In this region, eight novel mutations were identified and classified as likely pathogenic driver variants. In addition, the present study identified 6 patients with secondary KIT mutation and 1 patient with double mutant GIST, who had two different mutations in PDGFRA exon 14.\n

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\n \n\n \n \n \n \n \n Mutational Profiling of Driver Tumor Suppressor and Oncogenic Genes in Brazilian Malignant Pleural Mesotheliomas.\n \n \n \n\n\n \n Campanella, N. C.; Silva, E. C.; Dix, G.; de Lima Vazquez, F.; Escremim de Paula, F.; Berardinelli, G. N.; Balancin, M.; Chammas, R.; Mendoza Lopez, R. V.; Silveira, H. C. S.; Capelozzi, V. L.; and Reis, R. M.\n\n\n \n\n\n\n Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology, 87(3): 208–216. May 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{campanella_mutational_2020,\n\ttitle = {Mutational {Profiling} of {Driver} {Tumor} {Suppressor} and {Oncogenic} {Genes} in {Brazilian} {Malignant} {Pleural} {Mesotheliomas}},\n\tvolume = {87},\n\tissn = {1423-0291},\n\tdoi = {10.1159/000507373},\n\tabstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly lethal disease comprising a heterogeneous group of tumors with challenging to predict biological behavior. The diagnosis is complex, and the histologic classification includes 2 major subtypes of MPM: epithelioid (∼60\\% of cases) and sarcomatous (∼20\\%). Its identification depends upon pathological investigation supported by clinical and radiological evidence and more recently ancillary molecular testing. Treatment options are currently limited, with no known targeted therapies available.\nOBJECTIVES: To elucidate the mutation profile of driver tumor suppressor and oncogenic genes in a cohort of Brazilian patients.\nMETHODS: We sequenced 16 driver genes in a series of 43 Brazilian malignant mesothelioma (MM) patients from 3 distinct Brazilian centers. Genomic DNA was extracted from formalin-fixed paraffin-embedded tumor tissue blocks, and the TERT promoter region was amplified by PCR followed by direct capillary sequencing. The Illumina TruSight Tumor 15 was used to evaluate 250 amplicons from 15 genes associated with solid tumors (AKT1, GNA11, NRAS, BRAF, GNAQ, PDGFRA, EGFR, KIT, PIK3CA, ERBB2, KRAS, RET, FOXL2, MET,and TP53). Library preparation with the TruSight Tumor 15 was performed before sequencing at the MiSeq platform. Data analysis was performed using Sophia DDM software.\nRESULTS: Out of 43 MPM patients, 38 (88.4\\%) were epithelioid subtype and 5 (11.6\\%) were sarcomatoid histotype. Asbestos exposure was present in 15 (39.5\\%) patients with epithelioid MPM and 3 (60\\%) patients with sarcomatoid MPM. We found a TERT promoter mutation in 11.6\\% of MM, and the c.-146C{\\textgreater}T mutation was the most common event. The next-generation sequencing was successful in 33 cases. A total of 18 samples showed at least 1 pathogenic, with a median of 1.8 variants, ranging from 1 to 6. The most mutated genes were TP53 and ERBB2 with 7 variants each, followed by NRAS BRAF, PI3KCA, EGFR and PDGFRA with 2 variants each. KIT, AKT1, and FOXL2 genes exhibited 1 variant each. Interestingly, 2 variants observed in the PDGFRA gene are classic imatinib-sensitive therapy.\nCONCLUSIONS: We concluded that Brazilian MPM harbor mutation in classic tumor suppressor and oncogenic genes, which might help in the guidance of personalized treatment of MPM.},\n\tlanguage = {eng},\n\tnumber = {3},\n\tjournal = {Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology},\n\tauthor = {Campanella, Nathália C. and Silva, Eduardo Caetano and Dix, Gustavo and de Lima Vazquez, Fabiana and Escremim de Paula, Flávia and Berardinelli, Gustavo N. and Balancin, Marcelo and Chammas, Roger and Mendoza Lopez, Rossana V. and Silveira, Henrique César S. and Capelozzi, Vera Luiza and Reis, Rui Manuel},\n\tmonth = may,\n\tyear = {2020},\n\tpmid = {32369821},\n\tkeywords = {Asbestos, Malignant mesothelioma, Mutation, Next-generation sequencing, Oncogenes, SOPHiA DDM, TST15, Tumor suppressor genes},\n\tpages = {208--216},\n}\n\n

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\n BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly lethal disease comprising a heterogeneous group of tumors with challenging to predict biological behavior. The diagnosis is complex, and the histologic classification includes 2 major subtypes of MPM: epithelioid (∼60% of cases) and sarcomatous (∼20%). Its identification depends upon pathological investigation supported by clinical and radiological evidence and more recently ancillary molecular testing. Treatment options are currently limited, with no known targeted therapies available. OBJECTIVES: To elucidate the mutation profile of driver tumor suppressor and oncogenic genes in a cohort of Brazilian patients. METHODS: We sequenced 16 driver genes in a series of 43 Brazilian malignant mesothelioma (MM) patients from 3 distinct Brazilian centers. Genomic DNA was extracted from formalin-fixed paraffin-embedded tumor tissue blocks, and the TERT promoter region was amplified by PCR followed by direct capillary sequencing. The Illumina TruSight Tumor 15 was used to evaluate 250 amplicons from 15 genes associated with solid tumors (AKT1, GNA11, NRAS, BRAF, GNAQ, PDGFRA, EGFR, KIT, PIK3CA, ERBB2, KRAS, RET, FOXL2, MET,and TP53). Library preparation with the TruSight Tumor 15 was performed before sequencing at the MiSeq platform. Data analysis was performed using Sophia DDM software. RESULTS: Out of 43 MPM patients, 38 (88.4%) were epithelioid subtype and 5 (11.6%) were sarcomatoid histotype. Asbestos exposure was present in 15 (39.5%) patients with epithelioid MPM and 3 (60%) patients with sarcomatoid MPM. We found a TERT promoter mutation in 11.6% of MM, and the c.-146C\\textgreaterT mutation was the most common event. The next-generation sequencing was successful in 33 cases. A total of 18 samples showed at least 1 pathogenic, with a median of 1.8 variants, ranging from 1 to 6. The most mutated genes were TP53 and ERBB2 with 7 variants each, followed by NRAS BRAF, PI3KCA, EGFR and PDGFRA with 2 variants each. KIT, AKT1, and FOXL2 genes exhibited 1 variant each. Interestingly, 2 variants observed in the PDGFRA gene are classic imatinib-sensitive therapy. CONCLUSIONS: We concluded that Brazilian MPM harbor mutation in classic tumor suppressor and oncogenic genes, which might help in the guidance of personalized treatment of MPM.\n

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\n \n\n \n \n \n \n \n Insights into the pathophysiology of DFNA10 hearing loss associated with novel EYA4 variants.\n \n \n \n\n\n \n Morín, M.; Borreguero, L.; Booth, K. T.; Lachgar, M.; Huygen, P.; Villamar, M.; Mayo, F.; Barrio, L. C.; Santos Serrão de Castro, L.; Morales, C.; Del Castillo, I.; Arellano, B.; Tellería, D.; Smith, R. J. H.; Azaiez, H.; and Moreno Pelayo, M. A.\n\n\n \n\n\n\n Scientific Reports, 10(1): 6213. April 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{morin_insights_2020,\n\ttitle = {Insights into the pathophysiology of {DFNA10} hearing loss associated with novel {EYA4} variants},\n\tvolume = {10},\n\tissn = {2045-2322},\n\tdoi = {10.1038/s41598-020-63256-5},\n\tabstract = {The mutational spectrum of many genes and their contribution to the global prevalence of hereditary hearing loss is still widely unknown. In this study, we have performed the mutational screening of EYA4 gene by DHLPC and NGS in a large cohort of 531 unrelated Spanish probands and one Australian family with autosomal dominant non-syndromic hearing loss (ADNSHL). In total, 9 novel EYA4 variants have been identified, 3 in the EYA4 variable region (c.160G {\\textgreater} T; p.Glu54*, c.781del; p.Thr261Argfs*34 and c.1078C {\\textgreater} A; p.Pro360Thr) and 6 in the EYA-HR domain (c.1107G {\\textgreater} T; p.Glu369Asp, c.1122G {\\textgreater} T; p.Trp374Cys, c.1281G {\\textgreater} A; p.Glu427Glu, c.1282-1G {\\textgreater} A, c.1601C {\\textgreater} G; p.S534* and an heterozygous copy number loss encompassing exons 15 to 17). The contribution of EYA4 mutations to ADNSHL in Spain is, therefore, very limited ({\\textasciitilde}1.5\\%, 8/531). The pathophysiology of some of these novel variants has been explored. Transient expression of the c-myc-tagged EYA4 mutants in mammalian COS7 cells revealed absence of expression of the p.S534* mutant, consistent with a model of haploinsufficiency reported for all previously described EYA4 truncating mutations. However, normal expression pattern and translocation to the nucleus were observed for the p.Glu369Asp mutant in presence of SIX1. Complementary in silico analysis suggested that c.1107G {\\textgreater} T (p.Glu369Asp), c.1281G {\\textgreater} A (p.Glu427Glu) and c.1282-1G {\\textgreater} A variants alter normal splicing. Minigene assays in NIH3T3 cells further confirmed that all 3 variants caused exon skipping resulting in frameshifts that lead to premature stop codons. Our study reports the first likely pathogenic synonymous variant linked to DFNA10 and provide further evidence for haploinsufficiency as the common underlying disease-causing mechanism for DFNA10-related hearing loss.},\n\tlanguage = {eng},\n\tnumber = {1},\n\tjournal = {Scientific Reports},\n\tauthor = {Morín, Matias and Borreguero, Lucía and Booth, Kevin T. and Lachgar, María and Huygen, Patrick and Villamar, Manuela and Mayo, Fernando and Barrio, Luis Carlos and Santos Serrão de Castro, Luciana and Morales, Carmelo and Del Castillo, Ignacio and Arellano, Beatriz and Tellería, Dolores and Smith, Richard J. H. and Azaiez, Hela and Moreno Pelayo, M. A.},\n\tmonth = apr,\n\tyear = {2020},\n\tpmid = {32277154},\n\tpmcid = {PMC7148344},\n\tpages = {6213},\n}\n\n

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\n \n\n \n \n \n \n \n Assessment of the clinical utility of four NGS panels in myeloid malignancies. Suggestions for NGS panel choice or design.\n \n \n \n\n\n \n Aguilera-Diaz, A.; Vazquez, I.; Ariceta, B.; Mañú, A.; Blasco-Iturri, Z.; Palomino-Echeverría, S.; Larrayoz, M. J.; García-Sanz, R.; Prieto-Conde, M. I.; Del Carmen Chillón, M.; Alfonso-Pierola, A.; Prosper, F.; Fernandez-Mercado, M.; and Calasanz, M. J.\n\n\n \n\n\n\n PloS One, 15(1): e0227986. January 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 4 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{aguilera-diaz_assessment_2020,\n\ttitle = {Assessment of the clinical utility of four {NGS} panels in myeloid malignancies. {Suggestions} for {NGS} panel choice or design},\n\tvolume = {15},\n\tissn = {1932-6203},\n\tdoi = {10.1371/journal.pone.0227986},\n\tabstract = {The diagnosis of myeloid neoplasms (MN) has significantly evolved through the last few decades. Next Generation Sequencing (NGS) is gradually becoming an essential tool to help clinicians with disease management. To this end, most specialized genetic laboratories have implemented NGS panels targeting a number of different genes relevant to MN. The aim of the present study is to evaluate the performance of four different targeted NGS gene panels based on their technical features and clinical utility. A total of 32 patient bone marrow samples were accrued and sequenced with 3 commercially available panels and 1 custom panel. Variants were classified by two geneticists based on their clinical relevance in MN. There was a difference in panel's depth of coverage. We found 11 discordant clinically relevant variants between panels, with a trend to miss long insertions. Our data show that there is a high risk of finding different mutations depending on the panel of choice, due both to the panel design and the data analysis method. Of note, CEBPA, CALR and FLT3 genes, remains challenging the use of NGS for diagnosis of MN in compliance with current guidelines. Therefore, conventional molecular testing might need to be kept in place for the correct diagnosis of MN for now.},\n\tlanguage = {eng},\n\tnumber = {1},\n\tjournal = {PloS One},\n\tauthor = {Aguilera-Diaz, Almudena and Vazquez, Iria and Ariceta, Beñat and Mañú, Amagoia and Blasco-Iturri, Zuriñe and Palomino-Echeverría, Sara and Larrayoz, María José and García-Sanz, Ramón and Prieto-Conde, María Isabel and Del Carmen Chillón, María and Alfonso-Pierola, Ana and Prosper, Felipe and Fernandez-Mercado, Marta and Calasanz, María José},\n\tmonth = jan,\n\tyear = {2020},\n\tpmid = {31978184},\n\tpmcid = {PMC6980571},\n\tkeywords = {Benchmark, Genes, Neoplasm, Genomics, High-Throughput Nucleotide Sequencing, Humans, Leukemia, Myeloid, Liquid Biopsy, Liquid tumor, MYS, Mutation, Oncology, Targeted},\n\tpages = {e0227986},\n}\n\n

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\n \n\n \n \n \n \n \n \n A Population-Based Analysis of Outcomes in Patients with Enteropathy-Associated T-cell Lymphoma (EATL).\n \n \n \n \n\n\n \n Anusim, N.; Antonios, B.; Gupta, R.; Jindal, V.; Khoury, J.; and Jaiyesimi, I.\n\n\n \n\n\n\n American Journal of Hematology, 95(S1): S3–S38. October 2020.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajh.26005\n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{anusim_population-based_2020,\n\ttitle = {A {Population}-{Based} {Analysis} of {Outcomes} in {Patients} with {Enteropathy}-{Associated} {T}-cell {Lymphoma} ({EATL})},\n\tvolume = {95},\n\tcopyright = {© 2020 Wiley Periodicals LLC.},\n\tissn = {1096-8652},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/ajh.26005},\n\tdoi = {https://doi.org/10.1002/ajh.26005},\n\tabstract = {Background: EATL is very rare and accounts for less than 1 percent of all non-Hodgkin lymphomas. EATL occurs most commonly in patients with celiac disease and carries a uniformly poor prognosis. The optimal treatment for EATL is unclear and the data is limited to case reports and small retrospective studies.\n\nMethods: ICD-O-3 (9717) histological code was used to identify cases of EATL from the population-based cancer registries of the Surveillance Epidemiology and End Results program (SEER) between 2006 and 2016. Frequency, demographics, and survival data were assessed using SPSS statistical software.\n\nResults: A total of 138 cases were found. The median age of diagnosis was 66. EATL was more common in men (54.3\\%) and in Caucasians (76.8\\%). Of all EATL cases, 53.6\\% received chemotherapy and only 3.6\\% received radiation therapy. EATL was the cause of death in 58 \\% of the cases. Median overall survival (OS) was 3 months; 95\\% CI, (1.4 to 4.5 months) and disease specific overall survival (DSOS) was 8 months; 95\\% CI, (3.8 to 12.1 months). Chemotherapy significantly improved both OS (7 months vs 1 month; P{\\textless} 0.001) and DSOS (12 months vs 6 months; P=0.005). Multivariable analysis demonstrated that age, sex, race and radiation therapy were not associated with mortality. Chemotherapy was associated with decreased mortality risk (HR, 0.48; CI, 0.32 -0.71; p{\\textless} 0.001)\n\nConclusions: EATL is a rare subtype of non-Hodgkin lymphoma. Despite the advances in treating non-Hodgkin lymphomas, EATL prognosis remains poor. In concordance with previously reported data, chemotherapy has shown to mitigate the poor prognosis associated with EATL in our study.},\n\tlanguage = {en},\n\tnumber = {S1},\n\turldate = {2021-05-20},\n\tjournal = {American Journal of Hematology},\n\tauthor = {Anusim, Nwabundo and Antonios, Bana and Gupta, Ruby and Jindal, Vishal and Khoury, John and Jaiyesimi, Ishmael},\n\tmonth = oct,\n\tyear = {2020},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajh.26005},\n\tkeywords = {MYS},\n\tpages = {S3--S38},\n}\n\n

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\n \n\n \n \n \n \n \n \n Ethnicity-related DMD Genotype Landscapes in European and Non-European Countries.\n \n \n \n \n\n\n \n Selvatici, R.; Rossi, R.; Fortunato, F.; Trabanelli, C.; Sifi, Y.; Margutti, A.; Neri, M.; Gualandi, F.; Szabò, L.; Fekete, B.; Angelova, L.; Litvinenko, I.; Ivanov, I.; Vildan, Y.; Iuhas, O. A.; Vintan, M.; Burloiu, C.; Lacramioara, B.; Visa, G.; Epure, D.; Rusu, C.; Vasile, D.; Sandu, M.; Vlodavets, D.; Mager, M.; Kyriakides, T.; Delin, S.; Lehman, I.; Fureš, J. S.; Bojinova, V.; Militaru, M.; Guergueltcheva, V.; Burnyte, B.; Molnar, M. J.; Butoianu, N.; Bensemmane, S. D.; Makri-Mokrane, S.; Herczegfalvi, A.; Panzaru, M.; Emandi, A. C.; Lusakowska, A.; Potulska-Chromik, A.; Kostera-Pruszczyk, A.; Shatillo, A.; Khelladi, D. B.; Dendane, O.; Fang, M.; Lu, Z.; and Ferlini, A.\n\n\n \n\n\n\n Neurology Genetics, 7(1). December 2020.\n Publisher: Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology Section: Article\n\n\n\n
\n\n\n\n \n \n $\"Ethnicity-related$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{selvatici_ethnicity-related_2020,\n\ttitle = {Ethnicity-related {DMD} {Genotype} {Landscapes} in {European} and {Non}-{European} {Countries}},\n\tvolume = {7},\n\tcopyright = {© 2020 American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.},\n\tissn = {2376-7839},\n\turl = {https://ng.neurology.org/content/7/1/e536},\n\tdoi = {10.1212/NXG.0000000000000536},\n\tabstract = {Objective Genetic diagnosis and mutation identification are now compulsory for Duchenne (DMD) and Becker muscular dystrophies (BMD), which are due to dystrophin (DMD) gene mutations, either for disease prevention or personalized therapies. To evaluate the ethnic-related genetic assortments of DMD mutations, which may impact on DMD genetic diagnosis pipelines, we studied 328 patients with DMD and BMD from non-European countries.\nMethods We performed a full DMD mutation detection in 328 patients from 10 Eastern European countries (Poland, Hungary, Lithuania, Romania, Serbia, Croatia, Bosnia, Bulgaria, Ukraine, and Russia) and 2 non-European countries (Cyprus and Algeria). We used both conventional methods (multiplex ligation-dependent probe amplification [MLPA] followed by gene-specific sequencing) and whole-exome sequencing (WES) as a pivotal study ran in 28 patients where DMD mutations were already identified by standard techniques. WES output was also interrogated for DMD gene modifiers.\nResults We identified DMD gene mutations in 222 male patients. We identified a remarkable allele heterogeneity among different populations with a mutation landscape often country specific. We also showed that WES is effective for picking up all DMD deletions and small mutations and its adoption could allow a detection rate close to 90\\% of all occurring mutations. Gene modifiers haplotypes were identified with some ethnic-specific configurations.\nConclusions Our data provide unreported mutation landscapes in different countries, suggesting that ethnicity may orient genetic diagnosis flowchart, which can be adjusted depending on the mutation type frequency, with impact in drug eligibility.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2021-01-04},\n\tjournal = {Neurology Genetics},\n\tauthor = {Selvatici, Rita and Rossi, Rachele and Fortunato, Fernanda and Trabanelli, Cecilia and Sifi, Yamina and Margutti, Alice and Neri, Marcella and Gualandi, Francesca and Szabò, Lena and Fekete, Balint and Angelova, Lyudmilla and Litvinenko, Ivan and Ivanov, Ivan and Vildan, Yurtsever and Iuhas, Oana Alexandra and Vintan, Mihaela and Burloiu, Carmen and Lacramioara, Butnariu and Visa, Gabriela and Epure, Diana and Rusu, Cristina and Vasile, Daniela and Sandu, Magdalena and Vlodavets, Dmitry and Mager, Monica and Kyriakides, Theodore and Delin, Sanja and Lehman, Ivan and Fureš, Jadranka Sekelj and Bojinova, Veneta and Militaru, Mariela and Guergueltcheva, Velina and Burnyte, Birute and Molnar, Maria Judith and Butoianu, Niculina and Bensemmane, Selma Dounia and Makri-Mokrane, Samira and Herczegfalvi, Agnes and Panzaru, Monica and Emandi, Adela Chirita and Lusakowska, Anna and Potulska-Chromik, Anna and Kostera-Pruszczyk, Anna and Shatillo, Andriy and Khelladi, Djawed Bouchenak and Dendane, Oussama and Fang, Mingyan and Lu, Zhiyuan and Ferlini, Alessandra},\n\tmonth = dec,\n\tyear = {2020},\n\tnote = {Publisher: Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology\nSection: Article},\n\tkeywords = {SOPHiA DDM},\n}\n\n

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\n \n\n \n \n \n \n \n \n Verification of the Dutch criteria for familial hypercholesterolemia among a contingent of patients in Southern Bulgaria.\n \n \n \n \n\n\n \n Kitova, L. G.; Assenova, R. S.; Dobreva, B. V.; and Kitov, S. I.\n\n\n \n\n\n\n Atherosclerosis, 315: e210. December 2020.\n Publisher: Elsevier\n\n\n\n
\n\n\n\n \n \n $\"Verification$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 7 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{kitova_verification_2020,\n\ttitle = {Verification of the {Dutch} criteria for familial hypercholesterolemia among a contingent of patients in {Southern} {Bulgaria}},\n\tvolume = {315},\n\tissn = {0021-9150, 1879-1484},\n\turl = {https://www.atherosclerosis-journal.com/article/S0021-9150(20)31238-7/abstract},\n\tdoi = {10.1016/j.atherosclerosis.2020.10.656},\n\tabstract = {Background and Aims: The Dutch criteria for FH are routinely used in everyday practice\nin Bulgaria. The goal of the study was to detect patients with Familial hypercholesterolemia\nin the outpatient care system through application of the Dutch criteria and to verify\nthat with genetic analysis.},\n\tlanguage = {English},\n\turldate = {2021-01-04},\n\tjournal = {Atherosclerosis},\n\tauthor = {Kitova, L. G. and Assenova, R. S. and Dobreva, B. V. and Kitov, S. I.},\n\tmonth = dec,\n\tyear = {2020},\n\tnote = {Publisher: Elsevier},\n\tkeywords = {SOPHiA DDM},\n\tpages = {e210},\n}\n\n

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\n \n\n \n \n \n \n \n \n Genetic analysis of a rare form of dyslipidemia: Sitosterolemia in a Greek patient.\n \n \n \n \n\n\n \n Koniari, E.; Skouma, A.; Dragoti, A.; Oikonomaki, K.; Constantoulakis, P.; and Chrousos, G.\n\n\n \n\n\n\n Atherosclerosis, 315: e210. December 2020.\n Publisher: Elsevier\n\n\n\n
\n\n\n\n \n \n $\"Genetic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{koniari_genetic_2020,\n\ttitle = {Genetic analysis of a rare form of dyslipidemia: {Sitosterolemia} in a {Greek} patient},\n\tvolume = {315},\n\tissn = {0021-9150, 1879-1484},\n\tshorttitle = {Genetic analysis of a rare form of dyslipidemia},\n\turl = {https://www.atherosclerosis-journal.com/article/S0021-9150(20)31240-5/abstract},\n\tdoi = {10.1016/j.atherosclerosis.2020.10.658},\n\tabstract = {Background and Aims: Sitosterolemia is a rare autosomal recessive inherited metabolic\ndisorder of lipids, characterized by particularly elevated levels of plant sterols\nin plasma. The disease is underdiagnosed as it is often treated as common dyslipidaemia.},\n\tlanguage = {English},\n\turldate = {2021-01-04},\n\tjournal = {Atherosclerosis},\n\tauthor = {Koniari, E. and Skouma, A. and Dragoti, A. and Oikonomaki, K. and Constantoulakis, P. and Chrousos, G.},\n\tmonth = dec,\n\tyear = {2020},\n\tnote = {Publisher: Elsevier},\n\tkeywords = {SOPHiA DDM},\n\tpages = {e210},\n}\n\n

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\n \n\n \n \n \n \n \n \n Detection of a new mutation in the apoB gene: A case report of a pediatric patient with familial hypobetalipoproteinemia (FHBL).\n \n \n \n \n\n\n \n Koniari, E.; Skouma, A.; Zarkada, I.; Dragoti, A.; Constantoulakis, P.; Samara, S.; and Chrousos, G.\n\n\n \n\n\n\n Atherosclerosis, 315: e210. December 2020.\n Publisher: Elsevier\n\n\n\n
\n\n\n\n \n \n $\"Detection$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{koniari_detection_2020,\n\ttitle = {Detection of a new mutation in the {apoB} gene: {A} case report of a pediatric patient with familial hypobetalipoproteinemia ({FHBL})},\n\tvolume = {315},\n\tissn = {0021-9150, 1879-1484},\n\tshorttitle = {Detection of a new mutation in the {apoB} gene},\n\turl = {https://www.atherosclerosis-journal.com/article/S0021-9150(20)31239-9/abstract},\n\tdoi = {10.1016/j.atherosclerosis.2020.10.657},\n\tabstract = {Background and Aims: Hypolipidemias are metabolic disorders that are generally underdiagnosed\nand therefore not treated properly. Low levels of lipids and lipoproteins result in\nsevere morbidity.},\n\tlanguage = {English},\n\turldate = {2021-01-04},\n\tjournal = {Atherosclerosis},\n\tauthor = {Koniari, E. and Skouma, A. and Zarkada, I. and Dragoti, A. and Constantoulakis, P. and Samara, S. and Chrousos, G.},\n\tmonth = dec,\n\tyear = {2020},\n\tnote = {Publisher: Elsevier},\n\tkeywords = {SOPHiA DDM},\n\tpages = {e210},\n}\n\n

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\n \n\n \n \n \n \n \n \n Clinical characteristics of patients with familial hypercholesterolemia: Data from the HELLAS-FH registry.\n \n \n \n \n\n\n \n Rizos, C.; Liamis, G.; Skoumas, I.; Rallidis, L.; Tziomalos, K.; Skalides, E.; Kotsis, V.; Garoufi, A.; Athyros, V. G.; Kolovou, G.; Sfikas, G.; Bilianou, E.; Koutagiar, I.; Kiouri, E.; Agapakis, D.; Zacharis, E.; Antza, C.; Attilakos, A.; Katsiki, N.; Anagnostis, P.; Koumaras, C.; and Liberopoulos, E.\n\n\n \n\n\n\n Atherosclerosis, 315: e210–e211. December 2020.\n Publisher: Elsevier\n\n\n\n
\n\n\n\n \n \n $\"Clinical$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{rizos_clinical_2020,\n\ttitle = {Clinical characteristics of patients with familial hypercholesterolemia: {Data} from the {HELLAS}-{FH} registry},\n\tvolume = {315},\n\tissn = {0021-9150, 1879-1484},\n\tshorttitle = {Clinical characteristics of patients with familial hypercholesterolemia},\n\turl = {https://www.atherosclerosis-journal.com/article/S0021-9150(20)31241-7/abstract},\n\tdoi = {10.1016/j.atherosclerosis.2020.10.659},\n\tabstract = {Background and Aims: Familial hypercholesterolemia (FH) is characterized by a high\nprevalence of cardiovascular disease (CVD). The aim of this study was to investigate\nthe correlation between CVD incidence and clinical features in adult FH patients participating\nin the HELLAS FH registry.},\n\tlanguage = {English},\n\turldate = {2021-01-04},\n\tjournal = {Atherosclerosis},\n\tauthor = {Rizos, C. and Liamis, G. and Skoumas, I. and Rallidis, L. and Tziomalos, K. and Skalides, E. and Kotsis, V. and Garoufi, A. and Athyros, V. G. and Kolovou, G. and Sfikas, G. and Bilianou, E. and Koutagiar, I. and Kiouri, E. and Agapakis, D. and Zacharis, E. and Antza, C. and Attilakos, A. and Katsiki, N. and Anagnostis, P. and Koumaras, C. and Liberopoulos, E.},\n\tmonth = dec,\n\tyear = {2020},\n\tnote = {Publisher: Elsevier},\n\tkeywords = {SOPHiA DDM},\n\tpages = {e210--e211},\n}\n\n

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\n \n\n \n \n \n \n \n The First Case of Congenital Myasthenic Syndrome Caused by a Large Homozygous Deletion in the C-Terminal Region of COLQ (Collagen Like Tail Subunit of Asymmetric Acetylcholinesterase) Protein.\n \n \n \n\n\n \n Laforgia, N.; De Cosmo, L.; Palumbo, O.; Ranieri, C.; Sesta, M.; Capodiferro, D.; Pantaleo, A.; Iapicca, P.; Lastella, P.; Capozza, M.; Schettini, F.; Bukvic, N.; Bagnulo, R.; and Resta, N.\n\n\n \n\n\n\n Genes, 11(12). December 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{laforgia_first_2020,\n\ttitle = {The {First} {Case} of {Congenital} {Myasthenic} {Syndrome} {Caused} by a {Large} {Homozygous} {Deletion} in the {C}-{Terminal} {Region} of {COLQ} ({Collagen} {Like} {Tail} {Subunit} of {Asymmetric} {Acetylcholinesterase}) {Protein}},\n\tvolume = {11},\n\tissn = {2073-4425},\n\tdoi = {10.3390/genes11121519},\n\tabstract = {Congenital myasthenic syndromes (CMSs) are caused by mutations in genes that encode proteins involved in the organization, maintenance, function, or modification of the neuromuscular junction. Among these, the collagenic tail of endplate acetylcholinesterase protein (COLQ; MIM 603033) has a crucial role in anchoring the enzyme into the synaptic basal lamina. Here, we report on the first case of a patient with a homozygous deletion affecting the last exons of the COLQ gene in a CMS patient born to consanguineous parents of Pakistani origin. Electromyography (EMG), electroencephalography (EEG), clinical exome sequencing (CES), and single nucleotide polymorphism (SNP) array analyses were performed. The subject was born at term after an uneventful pregnancy and developed significant hypotonia and dystonia, clinical pseudoseizures, and recurring respiratory insufficiency with a need for mechanical ventilation. CES analysis of the patient revealed a homozygous deletion of the COLQ gene located on the 3p25.1 chromosome region. The SNP-array confirmed the presence of deletion that extended from exon 11 to the last exon 17 with a size of 19.5 Kb. Our results add new insights about the underlying pathogenetic mechanisms expanding the spectrum of causative COLQ mutations. It is relevant, considering the therapeutic implications, to apply suitable molecular approaches so that no type of mutation is missed: "each lost mutation means a baby treated improperly".},\n\tlanguage = {eng},\n\tnumber = {12},\n\tjournal = {Genes},\n\tauthor = {Laforgia, Nicola and De Cosmo, Lucrezia and Palumbo, Orazio and Ranieri, Carlotta and Sesta, Michela and Capodiferro, Donatella and Pantaleo, Antonino and Iapicca, Pierluigi and Lastella, Patrizia and Capozza, Manuela and Schettini, Federico and Bukvic, Nenad and Bagnulo, Rosanna and Resta, Nicoletta},\n\tmonth = dec,\n\tyear = {2020},\n\tpmid = {33353066},\n\tpmcid = {PMC7765904},\n\tkeywords = {COLQ, SNP-array, SOPHiA DDM, clinical exome sequencing, congenital myasthenic syndrome},\n}\n\n

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\n \n\n \n \n \n \n \n Artificial Intelligence and Healthcare in Emerging Markets.\n \n \n \n\n\n \n Mrazek, M.; and O’Neill, F.\n\n\n \n\n\n\n ,8. September 2020.\n \n\n\n\n
\n\n\n\n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{mrazek_artificial_2020,\n\ttitle = {Artificial {Intelligence} and {Healthcare} in {Emerging} {Markets}},\n\tlanguage = {en},\n\tauthor = {Mrazek, Monique and O’Neill, Felicity},\n\tmonth = sep,\n\tyear = {2020},\n\tkeywords = {SOPHiA DDM},\n\tpages = {8},\n}\n\n

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\n \n\n \n \n \n \n \n Sensitivity and specificity of loss of heterozygosity analysis for the classification of rare germline variants in BRCA1/2: results of the observational AGO-TR1 study (NCT02222883).\n \n \n \n\n\n \n Hauke, J.; Harter, P.; Ernst, C.; Burges, A.; Schmidt, S.; Reuss, A.; Borde, J.; De Gregorio, N.; Dietrich, D.; El-Balat, A.; Kayali, M.; Gevensleben, H.; Hilpert, F.; Altmüller, J.; Heimbach, A.; Meier, W.; Schoemig-Markiefka, B.; Thiele, H.; Kimmig, R.; Nürnberg, P.; Kast, K.; Richters, L.; Sehouli, J.; Schmutzler, R. K.; and Hahnen, E.\n\n\n \n\n\n\n Journal of Medical Genetics. December 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{hauke_sensitivity_2020,\n\ttitle = {Sensitivity and specificity of loss of heterozygosity analysis for the classification of rare germline variants in {BRCA1}/2: results of the observational {AGO}-{TR1} study ({NCT02222883})},\n\tissn = {1468-6244},\n\tshorttitle = {Sensitivity and specificity of loss of heterozygosity analysis for the classification of rare germline variants in {BRCA1}/2},\n\tdoi = {10.1136/jmedgenet-2020-107353},\n\tabstract = {Variant-specific loss of heterozygosity (LOH) analyses may be useful to classify BRCA1/2 germline variants of unknown significance (VUS). The sensitivity and specificity of this approach, however, remains unknown. We performed comparative next-generation sequencing analyses of the BRCA1/2 genes using blood-derived and tumour-derived DNA of 488 patients with ovarian cancer enrolled in the observational AGO-TR1 trial (NCT02222883). Overall, 94 pathogenic, 90 benign and 24 VUS were identified in the germline. A significantly increased variant fraction (VF) of a germline variant in the tumour indicates loss of the wild-type allele; a decreased VF indicates loss of the variant allele. We demonstrate that significantly increased VFs predict pathogenicity with high sensitivity (0.84, 95\\% CI 0.77 to 0.91), poor specificity (0.63, 95\\% CI 0.53 to 0.73) and poor positive predictive value (PPV; 0.71, 95\\% CI 0.62 to 0.79). Significantly decreased VFs predict benignity with low sensitivity (0.26, 95\\% CI 0.17 to 0.35), high specificity (1.0, 95\\% CI 0.96 to 1.00) and PPV (1.0, 95\\% CI 0.85 to 1.00). Variant classification based on significantly increased VFs results in an unacceptable proportion of false-positive results. A significantly decreased VF in the tumour may be exploited as a reliable predictor for benignity, with no false-negative result observed. When applying the latter approach, VUS identified in four patients can now be considered benign. Trial registration number NCT02222883.},\n\tlanguage = {eng},\n\tjournal = {Journal of Medical Genetics},\n\tauthor = {Hauke, Jan and Harter, Philipp and Ernst, Corinna and Burges, Alexander and Schmidt, Sandra and Reuss, Alexander and Borde, Julika and De Gregorio, Nikolaus and Dietrich, Dimo and El-Balat, Ahmed and Kayali, Mohamad and Gevensleben, Heidrun and Hilpert, Felix and Altmüller, Janine and Heimbach, André and Meier, Werner and Schoemig-Markiefka, Birgid and Thiele, Holger and Kimmig, Rainer and Nürnberg, Peter and Kast, Karin and Richters, Lisa and Sehouli, Jalid and Schmutzler, Rita K. and Hahnen, Eric},\n\tmonth = dec,\n\tyear = {2020},\n\tpmid = {33273034},\n\tkeywords = {SOPHiA DDM, genetic predisposition to disease, genetic research, genetic testing, germ-line mutation},\n}\n\n

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\n \n\n \n \n \n \n \n \n Abstracts from the 53rd European Society of Human Genetics (ESHG) Conference: e-Posters.\n \n \n \n \n\n\n \n \n\n\n \n\n\n\n European Journal of Human Genetics, 28(Suppl 1): 798–1016. December 2020.\n \n\n\n\n
\n\n\n\n \n \n $\"Abstracts$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 5 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{noauthor_abstracts_2020,\n\ttitle = {Abstracts from the 53rd {European} {Society} of {Human} {Genetics} ({ESHG}) {Conference}: e-{Posters}},\n\tvolume = {28},\n\tissn = {1018-4813},\n\tshorttitle = {Abstracts from the 53rd {European} {Society} of {Human} {Genetics} ({ESHG}) {Conference}},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705408/},\n\tdoi = {10.1038/s41431-020-00741-5},\n\tnumber = {Suppl 1},\n\turldate = {2020-12-11},\n\tjournal = {European Journal of Human Genetics},\n\tmonth = dec,\n\tyear = {2020},\n\tpmid = {null},\n\tpmcid = {PMC7705408},\n\tkeywords = {CES, Clinical Exome, Exome, exome sequencing},\n\tpages = {798--1016},\n}\n\n

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\n \n\n \n \n \n \n \n Antigen Expression Varies Significantly between Molecular Subgroups of Acute Myeloid Leukemia Patients: Clinical Applicability Is Hampered by Establishment of Relevant Cutoffs.\n \n \n \n\n\n \n Herborg, L. L.; Nederby, L.; Brøndum, R. F.; Hansen, M.; Hokland, P.; and Roug, A. S.\n\n\n \n\n\n\n Acta Haematologica,1–10. December 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{herborg_antigen_2020,\n\ttitle = {Antigen {Expression} {Varies} {Significantly} between {Molecular} {Subgroups} of {Acute} {Myeloid} {Leukemia} {Patients}: {Clinical} {Applicability} {Is} {Hampered} by {Establishment} of {Relevant} {Cutoffs}},\n\tissn = {1421-9662},\n\tshorttitle = {Antigen {Expression} {Varies} {Significantly} between {Molecular} {Subgroups} of {Acute} {Myeloid} {Leukemia} {Patients}},\n\tdoi = {10.1159/000510504},\n\tabstract = {INTRODUCTION: In this single-center study of 268 acute myeloid leukemia (AML) patients, we have tested if a subset of 4 routinely employed immunophenotypic stem cell-associated markers correlated with the presence of recurrently mutated genes and if the markers were predictive for mutational status.\nMETHODS: Immunophenotypic data from 268 diagnostic AML samples obtained in 2009-2018 were analyzed retrospectively for the antigens CD34, CD117, CD123, and CLEC12A. Correlation between immunophenotypes and mutations was analyzed by Fischer's exact test. Clinical applicability of the markers for predicting mutational status was evaluated by receiver operating characteristics analyses, where an area under the curve (AUC) of at least 0.85 was accepted as clinically relevant.\nRESULTS: For a number of genes, the antigen expression differed significantly between mutated and wild-type gene expression. Despite low AUCs, CD123 and CLEC12A correlated with FLT3+NPM1- and FLT3+NPM1+. Three subsets met the AUC requirements (CD34+, CD34+CD117+, and CD34-CD117+) for predicting FLT3-NPM1+ or FLT3+NPM1+.\nCONCLUSION: The value of immunophenotypes as surrogate markers for mutational status in AML seems limited when employing CD123 and CLEC12A in combination with CD34 and CD117. Defining relevant cutoffs for given markers is challenging and hampered by variation between laboratories and patient groups.},\n\tlanguage = {eng},\n\tjournal = {Acta Haematologica},\n\tauthor = {Herborg, Laura Laine and Nederby, Line and Brøndum, Rasmus Froberg and Hansen, Maria and Hokland, Peter and Roug, Anne Stidsholt},\n\tmonth = dec,\n\tyear = {2020},\n\tpmid = {33271547},\n\tkeywords = {Acute myeloid leukemia, Flow cytometry, Immunophenotype, MYS+, Mutations, Myeloid, Prognosis},\n\tpages = {1--10},\n}\n\n

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\n \n\n \n \n \n \n \n \n Assessment of Minimal Residual Disease by Next Generation Sequencing in Peripheral Blood as a Complementary Tool for Personalized Transplant Monitoring in Myeloid Neoplasms.\n \n \n \n \n\n\n \n Aguirre-Ruiz, P.; Ariceta, B.; Viguria, M. C.; Zudaire, M. T.; Blasco-Iturri, Z.; Arnedo, P.; Aguilera-Diaz, A.; Jauregui, A.; Mañú, A.; Prosper, F.; Mateos, M. C.; Fernández-Mercado, M.; Larráyoz, M. J.; Redondo, M.; Calasanz, M. J.; Vázquez, I.; and Bandrés, E.\n\n\n \n\n\n\n Journal of Clinical Medicine, 9(12): 3818. November 2020.\n Number: 12 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Assessment$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 4 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{aguirre-ruiz_assessment_2020,\n\ttitle = {Assessment of {Minimal} {Residual} {Disease} by {Next} {Generation} {Sequencing} in {Peripheral} {Blood} as a {Complementary} {Tool} for {Personalized} {Transplant} {Monitoring} in {Myeloid} {Neoplasms}},\n\tvolume = {9},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\turl = {https://www.mdpi.com/2077-0383/9/12/3818},\n\tdoi = {10.3390/jcm9123818},\n\tabstract = {Patients with myeloid neoplasms who relapsed after allogenic hematopoietic stem cell transplant (HSCT) have poor prognosis. Monitoring of chimerism and specific molecular markers as a surrogate measure of relapse is not always helpful; therefore, improved systems to detect early relapse are needed. We hypothesized that the use of next generation sequencing (NGS) could be a suitable approach for personalized follow-up post-HSCT. To validate our hypothesis, we analyzed by NGS, a retrospective set of peripheral blood (PB) DNA samples previously evaluated by high-sensitive quantitative PCR analysis using insertion/deletion polymorphisms (indel-qPCR) chimerism engraftment. Post-HCST allelic burdens assessed by NGS and chimerism status showed a similar time-course pattern. At time of clinical relapse in 8/12 patients, we detected positive NGS-based minimal residual disease (NGS-MRD). Importantly, in 6/8 patients, we were able to detect NGS-MRD at time points collected prior to clinical relapse. We also confirmed the disappearance of post-HCST allelic burden in non-relapsed patients, indicating true clinical specificity. This study highlights the clinical utility of NGS-based post-HCST monitoring in myeloid neoplasia as a complementary specific analysis to high-sensitive engraftment testing. Overall, NGS-MRD testing in PB is widely applicable for the evaluation of patients following HSCT and highly valuable to personalized early treatment intervention when mixed chimerism is detected.},\n\tlanguage = {en},\n\tnumber = {12},\n\turldate = {2020-11-30},\n\tjournal = {Journal of Clinical Medicine},\n\tauthor = {Aguirre-Ruiz, Paula and Ariceta, Beñat and Viguria, María Cruz and Zudaire, María Teresa and Blasco-Iturri, Zuriñe and Arnedo, Patricia and Aguilera-Diaz, Almudena and Jauregui, Axier and Mañú, Amagoia and Prosper, Felipe and Mateos, María Carmen and Fernández-Mercado, Marta and Larráyoz, María José and Redondo, Margarita and Calasanz, María José and Vázquez, Iria and Bandrés, Eva},\n\tmonth = nov,\n\tyear = {2020},\n\tnote = {Number: 12\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {SOPHiA DDM, SOPHiA Fever \\& Auto Inflammatory Diseases, chimerism, hematopoietic stem cell transplant (HSCT), minimal residual disease (MRD), myeloid leukemia, next generation sequencing (NGS)},\n\tpages = {3818},\n}\n\n

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\n \n\n \n \n \n \n \n \n Transient expansion of TP53 mutated clones in polycythemia vera patients treated with idasanutlin.\n \n \n \n \n\n\n \n Marcellino, B. K.; Farnoud, N.; Cassinat, B.; Lu, M.; Verger, E.; McGovern, E.; Patel, M.; Medina-Martinez, J.; Levine, M. F.; Arango Ossa, J. E.; Zhou, Y.; Kosiorek, H.; Mehrotra, M.; Houldsworth, J.; Dueck, A.; Rossi, M.; Mascarenhas, J.; Kiladjian, J.; Rampal, R. K.; and Hoffman, R.\n\n\n \n\n\n\n Blood Advances, 4(22): 5735–5744. November 2020.\n \n\n\n\n
\n\n\n\n \n \n $\"Transient$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 4 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{marcellino_transient_2020,\n\ttitle = {Transient expansion of {TP53} mutated clones in polycythemia vera patients treated with idasanutlin},\n\tvolume = {4},\n\tissn = {2473-9529},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686898/},\n\tdoi = {10.1182/bloodadvances.2020002379},\n\tabstract = {Idasanutlin treatment of patients with PV promotes expansion of TP53 mutant subclones.\n            \n            \n              After cessation of idasanutlin treatment, the majority of TP53 mutant clones stabilize and decrease in size.\n            \n          \n        , Activation of the P53 pathway through inhibition of MDM2 using nutlins has shown clinical promise in the treatment of solid tumors and hematologic malignancies. There is concern, however, that nutlin therapy might stimulate the emergence or expansion of TP53-mutated subclones. We recently published the results of a phase 1 trial of idasanutlin in patients with polycythemia vera (PV) that revealed tolerability and clinical activity. Here, we present data indicating that idasanutlin therapy is associated with expansion of TP53 mutant subclones. End-of-study sequencing of patients found that 5 patients in this trial harbored 12 TP53 mutations; however, only 1 patient had been previously identified as having a TP53 mutation at baseline. To identify the origin of these mutations, further analysis of raw sequencing data of baseline samples was performed and revealed that a subset of these mutations was present at baseline and expanded during treatment with idasanutlin. Follow-up samples were obtained from 4 of 5 patients in this cohort, and we observed that after cessation of idasanutlin, the variant allele frequency (VAF) of 8 of 9 TP53 mutations decreased. Furthermore, disease progression to myelofibrosis or myeloproliferative neoplasm blast phase was not observed in any of these patients after 19- to 32-month observation. These data suggest that idasanutlin treatment may promote transient TP53 mutant clonal expansion. A larger study geared toward high-resolution detection of low VAF mutations is required to explore whether patients acquire de novo TP53 mutations after idasanutlin therapy.,},\n\tnumber = {22},\n\turldate = {2020-11-30},\n\tjournal = {Blood Advances},\n\tauthor = {Marcellino, Bridget K. and Farnoud, Noushin and Cassinat, Bruno and Lu, Min and Verger, Emanuelle and McGovern, Erin and Patel, Minal and Medina-Martinez, Juan and Levine, Max Fine and Arango Ossa, Juanes E. and Zhou, Yangyu and Kosiorek, Heidi and Mehrotra, Meenakshi and Houldsworth, Jane and Dueck, Amylou and Rossi, Michael and Mascarenhas, John and Kiladjian, Jean-Jacques and Rampal, Raajit K. and Hoffman, Ronald},\n\tmonth = nov,\n\tyear = {2020},\n\tpmid = {33216890},\n\tpmcid = {PMC7686898},\n\tkeywords = {Clinical study},\n\tpages = {5735--5744},\n}\n\n

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\n \n\n \n \n \n \n \n \n Comparison of the clinical diagnostic criteria and the results of the next-generation sequence gene panel in patients with monogenic systemic autoinflammatory diseases.\n \n \n \n \n\n\n \n Sözeri, B.; Demir, F.; Sönmez, H. E.; Karadağ, Ş. G.; Demirkol, Y. K.; Doğan, Ö. A.; Doğanay, H. L.; and Ayaz, N. A.\n\n\n \n\n\n\n Clinical Rheumatology. November 2020.\n \n\n\n\n
\n\n\n\n \n \n $\"Comparison$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 4 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{sozeri_comparison_2020,\n\ttitle = {Comparison of the clinical diagnostic criteria and the results of the next-generation sequence gene panel in patients with monogenic systemic autoinflammatory diseases},\n\tissn = {1434-9949},\n\turl = {https://doi.org/10.1007/s10067-020-05492-8},\n\tdoi = {10.1007/s10067-020-05492-8},\n\tabstract = {The clinicians initially prefer to define patients with the systemic autoinflammatory disease (SAID)’s based on recommended clinical classification criteria; then, they confirm the diagnosis with genetic testing. We aimed to compare the initial phenotypic diagnoses of the patients who were followed up with the preliminary diagnosis of a monogenic SAID, and the genotypic results obtained from the next-generation sequence (NGS) panel.},\n\tlanguage = {en},\n\turldate = {2020-11-30},\n\tjournal = {Clinical Rheumatology},\n\tauthor = {Sözeri, Betül and Demir, Ferhat and Sönmez, Hafize Emine and Karadağ, Şerife Gül and Demirkol, Yasemin Kendir and Doğan, Özlem Akgün and Doğanay, Hamdi Levent and Ayaz, Nuray Aktay},\n\tmonth = nov,\n\tyear = {2020},\n\tkeywords = {Custom Panel},\n}\n\n

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\n \n\n \n \n \n \n \n Clinical utility of Whole Exome Sequencing for rare Mendelian disorders: phenotypic-driven strategy for a high diagnostic yield and identification of 48 novel variants.\n \n \n \n\n\n \n Marinakis, N.; Veltra, D.; Sviggou, M.; Sofocleous, C.; Kekou, K.; Tsoutsou, E.; Kosma, K.; and Traeger-Synodinos, J.\n\n\n \n\n\n\n . November 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{marinakis_clinical_2020,\n\ttitle = {Clinical utility of {Whole} {Exome} {Sequencing} for rare {Mendelian} disorders: phenotypic-driven strategy for a high diagnostic yield and identification of 48 novel variants},\n\tdoi = {https://doi.org/10.22541/au.160425547.72459540/v1},\n\tabstract = {About 6,000 to 7,000 different rare disorders with suspected genetic etiologies have been described and in almost 4,500 of them the causative gene(s) have been identified. The advent of Next-Generation Sequencing (NGS) technologies has revolutionized genomic research and diagnostics, representing a major advance in identification of pathogenic genetic variations. WES facilitates a faster and more cost-effective route for definite diagnosis of rare genetic disorders, minimizing previous “diagnostic odysseys” for the patients. Due to the limitation that WES is not reimbursed in Greece, we aimed to minimize cost per patient/family through applying WES in the proband, followed by targeted family segregation studies when necessary. Furthermore, for variant filtration and interpretation we applied a phenotypic-driven strategy in close collaboration with clinical geneticists or referring clinicians. In this study we report the clinical application of WES in the diagnosis of 162 cases referred to investigate patients with undiagnosed genetic disorders. The overall molecular diagnostic yield reached 52.5\\%. Our experience as an academic diagnostic laboratory using WES, although limited to the last two years, allowed characterization of 94 pathogenic variants in 85 positive cases, 48 of which were novel, contributing information to the community of disease and variant databases.},\n\tauthor = {Marinakis, Nikolaos and Veltra, Danai and Sviggou, Maria and Sofocleous, Christalena and Kekou, Kyriaki and Tsoutsou, Eirini and Kosma, Konstantina and Traeger-Synodinos, Jan},\n\tmonth = nov,\n\tyear = {2020},\n\tkeywords = {WES},\n}\n\n

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\n \n\n \n \n \n \n \n NGS for (Hemato-) Oncology in Belgium: Evaluation of Laboratory Performance and Feasibility of a National External Quality Assessment Program.\n \n \n \n\n\n \n Delcourt, T.; Vanneste, K.; Soumali, M. R.; Coucke, W.; Ghislain, V.; Hebrant, A.; Van Valckenborgh, E.; De Keersmaecker, S. C. J.; Roosens, N. H.; Van De Walle, P.; Van Den Bulcke, M.; and Antoniou, A.\n\n\n \n\n\n\n Cancers, 12(11). October 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{delcourt_ngs_2020,\n\ttitle = {{NGS} for ({Hemato}-) {Oncology} in {Belgium}: {Evaluation} of {Laboratory} {Performance} and {Feasibility} of a {National} {External} {Quality} {Assessment} {Program}},\n\tvolume = {12},\n\tissn = {2072-6694},\n\tshorttitle = {{NGS} for ({Hemato}-) {Oncology} in {Belgium}},\n\tdoi = {10.3390/cancers12113180},\n\tabstract = {Next-generation sequencing (NGS) is being integrated into routine clinical practice in the field of (hemato-) oncology to search for variants with diagnostic, prognostic, or therapeutic value at potentially low allelic frequencies. The complex sequencing workflows used require careful validation and continuous quality control. Participation in external quality assessments (EQA) helps laboratories evaluate their performance and guarantee the validity of tests results with the ultimate goal of ensuring high-quality patient care. Here, we describe three benchmarking trials performed during the period 2017-2018 aiming firstly at establishing the state-of-the-art and secondly setting up a NGS-specific EQA program at the national level in the field of clinical (hemato-) oncology in Belgium. DNA samples derived from cell line mixes and artificially mutated cell lines, designed to carry variants of clinical relevance occurring in solid tumors, hematological malignancies, and BRCA1/BRCA2 genes, were sent to Belgian human genetics, anatomic pathology, and clinical biology laboratories, to be processed following routine practices, together with surveys covering technical aspects of the NGS workflows. Despite the wide variety of platforms and workflows currently applied in routine clinical practice, performance was satisfactory, since participating laboratories identified the targeted variants with success rates ranging between 93.06\\% and 97.63\\% depending on the benchmark, and few false negative or repeatability issues were identified. However, variant reporting and interpretation varied, underlining the need for further standardization. Our approach showcases the feasibility of developing and implementing EQA for routine clinical practice in the field of (hemato-) oncology, while highlighting the challenges faced.},\n\tlanguage = {eng},\n\tnumber = {11},\n\tjournal = {Cancers},\n\tauthor = {Delcourt, Thomas and Vanneste, Kevin and Soumali, Mohamed Rida and Coucke, Wim and Ghislain, Vanessa and Hebrant, Aline and Van Valckenborgh, Els and De Keersmaecker, Sigrid C. J. and Roosens, Nancy H. and Van De Walle, Philippe and Van Den Bulcke, Marc and Antoniou, Aline},\n\tmonth = oct,\n\tyear = {2020},\n\tpmid = {33138022},\n\tpmcid = {PMC7692129},\n\tkeywords = {Benchmark, SOPHiA DDM, cancer, external quality assessment, hemato-oncology, next-generation sequencing, oncology},\n}\n\n

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\n \n\n \n \n \n \n \n ctDNA in neuroendocrine carcinoma of gastroenteropancreatic origin or of unknown primary: the CIRCAN-NEC pilot study.\n \n \n \n\n\n \n Gerard, L.; Garcia, J.; Gauthier, A.; Lopez, J.; Durand, A.; Hervieu, V.; Lemelin, A.; Chardon, L.; Landel, V.; Gibert, B.; Lombard-Bohas, C.; Payen, L.; and Walter, T.\n\n\n \n\n\n\n Neuroendocrinology. October 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{gerard_ctdna_2020,\n\ttitle = {{ctDNA} in neuroendocrine carcinoma of gastroenteropancreatic origin or of unknown primary: the {CIRCAN}-{NEC} pilot study},\n\tissn = {1423-0194},\n\tshorttitle = {{ctDNA} in neuroendocrine carcinoma of gastroenteropancreatic origin or of unknown primary},\n\tdoi = {10.1159/000512502},\n\tabstract = {INTRODUCTION: Gastroenteropancreatic neuroendocrine carcinomas (GEPNEC) are characterised by a heterogeneous molecular profile and a poor prognosis. Circulating tumour DNA (ctDNA) analysis may be useful for NEC management. This study aimed at describing ctDNA mutations, to assess their predictive value for response to chemotherapies, and their change according to disease progression.\nMETHODS: The CIRCAN-NEC study included patients with GEPNEC or NEC from an unknown primary, scheduled to begin first or second-line chemotherapy. Blood samples were collected prior to chemotherapy initiation, at first evaluation, and during disease progression. ctDNA were sequenced by next-generation sequencing (NGS). Molecular response was defined as a decrease of at least 30\\% of the mutant allele fraction (MAF).\nRESULTS: All 24 patients included received platinum-etoposide first-line chemotherapy; 19 received a FOLFIRI-based post first-line regimen. Twenty-two patients had at least one driver mutation: TP53 (n=21), RB1 (n=2), KRAS (n=4), BRAF (n=3). Ten (42\\%) had a "adenocarcinoma-like" profile. Five of six patients with matching ctDNA/tissue NGS harboured at least one concordant mutation (44\\% concordance at the gene level). The concordance rate between ctDNA-mutation/immunohistochemistry-profile was 64\\% (7/11) for TP53/p53+ and 14\\% (1/7) for RB1/pRb-. In this pilot study including few patients by subgroups, patients with KRAS (HR=3.60, 95\\%CI [1.06-12.04]) and BRAF (HR=4.25, 95\\%CI [1.11-16.40]) mutations had shorter progression-free survival (PFS) under platinum-etoposide, while the two patients with RB1 mutations had shorter PFS under FOLFIRI-based chemotherapy. Twenty-eight periods of treatment were assessed: 10 patients had a molecular response (7/10 had a morphological response), which was associated with longer PFS (HR=0.37, 95\\%CI [0.15; 0.91]).\nCONCLUSION: This pilot study shows a high sensitivity of ctDNA assessment, which is encouraging for the future management of GEPNEC (tumour molecular diagnosis and evaluation of disease progression).},\n\tlanguage = {eng},\n\tjournal = {Neuroendocrinology},\n\tauthor = {Gerard, Laura and Garcia, Jessica and Gauthier, Arnaud and Lopez, Jonathan and Durand, Alice and Hervieu, Valérie and Lemelin, Annie and Chardon, Laurence and Landel, Verena and Gibert, Benjamin and Lombard-Bohas, Catherine and Payen, Lea and Walter, Thomas},\n\tmonth = oct,\n\tyear = {2020},\n\tpmid = {33099543},\n\tkeywords = {Custom Panel, SOPHiA DDM},\n}\n\n

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\n INTRODUCTION: Gastroenteropancreatic neuroendocrine carcinomas (GEPNEC) are characterised by a heterogeneous molecular profile and a poor prognosis. Circulating tumour DNA (ctDNA) analysis may be useful for NEC management. This study aimed at describing ctDNA mutations, to assess their predictive value for response to chemotherapies, and their change according to disease progression. METHODS: The CIRCAN-NEC study included patients with GEPNEC or NEC from an unknown primary, scheduled to begin first or second-line chemotherapy. Blood samples were collected prior to chemotherapy initiation, at first evaluation, and during disease progression. ctDNA were sequenced by next-generation sequencing (NGS). Molecular response was defined as a decrease of at least 30% of the mutant allele fraction (MAF). RESULTS: All 24 patients included received platinum-etoposide first-line chemotherapy; 19 received a FOLFIRI-based post first-line regimen. Twenty-two patients had at least one driver mutation: TP53 (n=21), RB1 (n=2), KRAS (n=4), BRAF (n=3). Ten (42%) had a \"adenocarcinoma-like\" profile. Five of six patients with matching ctDNA/tissue NGS harboured at least one concordant mutation (44% concordance at the gene level). The concordance rate between ctDNA-mutation/immunohistochemistry-profile was 64% (7/11) for TP53/p53+ and 14% (1/7) for RB1/pRb-. In this pilot study including few patients by subgroups, patients with KRAS (HR=3.60, 95%CI [1.06-12.04]) and BRAF (HR=4.25, 95%CI [1.11-16.40]) mutations had shorter progression-free survival (PFS) under platinum-etoposide, while the two patients with RB1 mutations had shorter PFS under FOLFIRI-based chemotherapy. Twenty-eight periods of treatment were assessed: 10 patients had a molecular response (7/10 had a morphological response), which was associated with longer PFS (HR=0.37, 95%CI [0.15; 0.91]). CONCLUSION: This pilot study shows a high sensitivity of ctDNA assessment, which is encouraging for the future management of GEPNEC (tumour molecular diagnosis and evaluation of disease progression).\n

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\n \n\n \n \n \n \n \n \n Genome‑wide methylation profiles in monozygotic twins with discordance for ovarian carcinoma.\n \n \n \n \n\n\n \n Erdogan, O. S.; Tuncer, S. B.; Kilic, S.; Odemis, D. A.; Turkcan, G. K.; Celik, B.; Avsar, M.; and Yazici, H.\n\n\n \n\n\n\n Oncology Letters, 20(6): 1–1. October 2020.\n Publisher: Spandidos Publications\n\n\n\n
\n\n\n\n \n \n $\"Genome‑wide$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 4 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{erdogan_genomewide_2020,\n\ttitle = {Genome‑wide methylation profiles in monozygotic twins with discordance for ovarian carcinoma},\n\tvolume = {20},\n\tissn = {1792-1074},\n\turl = {http://www.spandidos-publications.com/10.3892/ol.2020.12221/abstract},\n\tdoi = {10.3892/ol.2020.12221},\n\tnumber = {6},\n\turldate = {2020-10-20},\n\tjournal = {Oncology Letters},\n\tauthor = {Erdogan, Ozge Sukruoglu and Tuncer, Seref Bugra and Kilic, Seda and Odemis, Demet Akdeniz and Turkcan, Gozde Kuru and Celik, Betul and Avsar, Mukaddes and Yazici, Hulya},\n\tmonth = oct,\n\tyear = {2020},\n\tnote = {Publisher: Spandidos Publications},\n\tkeywords = {Ovarian Cancer, SOPHiA DDM},\n\tpages = {1--1},\n}\n\n

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\n \n\n \n \n \n \n \n An intronic variant in BRAT1 creates a cryptic splice site, causing epileptic encephalopathy without prominent rigidity.\n \n \n \n\n\n \n Colak, F. K.; Guleray, N.; Azapagasi, E.; Yazıcı, M. U.; Aksoy, E.; and Ceylan, N.\n\n\n \n\n\n\n Acta Neurologica Belgica. October 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{colak_intronic_2020,\n\ttitle = {An intronic variant in {BRAT1} creates a cryptic splice site, causing epileptic encephalopathy without prominent rigidity},\n\tissn = {2240-2993},\n\tdoi = {10.1007/s13760-020-01513-0},\n\tabstract = {BRAT1-related neurodevelopmental disorders are characterized by heterogeneous phenotypes with varying levels of clinical severity. Since the discovery of BRAT1 variants as the molecular etiology of lethal neonatal rigidity and multifocal seizure syndrome (RMFSL, OMIM 614498), these variants have also been identified in patients with milder clinical forms including neurodevelopmental disorder with cerebellar atrophy and with or without seizures (NEDCAS, OMIM 618056), epilepsy of infancy with migrating focal seizures (EIMFS), and congenital ataxia (CA). This study aims to examine the consequences and pathogenicity of a novel homozygous splice site variant in BRAT1 in a patient presenting with migrating focal seizures since birth without prominent rigidity. The patient was born from a consanguineous marriage and has had seizures since the neonatal period. He presented with dysmorphic features, pontocerebellar hypoplasia, and migrating focal seizures. Despite supportive treatment, his symptoms rapidly progressed to intractable myoclonic seizures, bouts of apnea and bradycardia, and arrest of head growth, with no acquisition of developmental milestones. Clinical exome sequencing yielded a novel homozygous splice variant in BRAT1. Genetic analysis based on reverse transcription of the patient's RNA followed by PCR amplifications performed on synthesized cDNA and Sanger sequencing was undertaken, and the functional effect of a BRAT1 variant on splicing machinery was demonstrated for the first time. The severe clinical presentation of migrating focal seizures and pontocerebellar hypoplasia in the absence of rigidity further expands the genotypic and phenotypic spectrum of BRAT1-related neurodevelopmental disorders.},\n\tlanguage = {eng},\n\tjournal = {Acta Neurologica Belgica},\n\tauthor = {Colak, Fatma Kurt and Guleray, Naz and Azapagasi, Ebru and Yazıcı, Mutlu Uysal and Aksoy, Erhan and Ceylan, Nesrin},\n\tmonth = oct,\n\tyear = {2020},\n\tpmid = {33040300},\n\tkeywords = {BRAT1, Migrating focal seizure, Pontocerebellar hypoplasia, SOPHiA DDM, Splice variant, TruSight},\n}\n\n

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\n \n\n \n \n \n \n \n \n New germline RAD51D gene variant in the Mongol breast cancer patients.\n \n \n \n \n\n\n \n Molokov, A.; Gervas, P.; and Cherdyntseva, N.\n\n\n \n\n\n\n European Journal of Cancer, 138: S79–S80. October 2020.\n Publisher: Elsevier\n\n\n\n
\n\n\n\n \n \n $\"New$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 4 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{molokov_new_2020,\n\ttitle = {New germline {RAD51D} gene variant in the {Mongol} breast cancer patients},\n\tvolume = {138},\n\tissn = {0959-8049, 1879-0852},\n\turl = {https://www.ejcancer.com/article/S0959-8049(20)30743-7/abstract},\n\tdoi = {10.1016/S0959-8049(20)30743-7},\n\tabstract = {Background: In recent decades, breast cancer (BC) is the most common malignancy in\nthe Russian Federation. The population is descended primarily from newcomers (Slavic\nancestors) and indigenous population (Mongoloid race). Currently, nothing is known\nregarding the molecular factors associated with increased risk of hereditary BC in\nthe indigenous population of Russia. BC prevention models for indigenous population\nhave not been developed yet. Our aim was to evaluate the frequency of hereditary mutations\nof RAD50 and RAD51D genes in Mongol BC patients.},\n\tlanguage = {English},\n\turldate = {2020-10-12},\n\tjournal = {European Journal of Cancer},\n\tauthor = {Molokov, A. and Gervas, P. and Cherdyntseva, N.},\n\tmonth = oct,\n\tyear = {2020},\n\tnote = {Publisher: Elsevier},\n\tpages = {S79--S80},\n}\n\n

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\n \n\n \n \n \n \n \n \n Non-BRCA hereditary gene mutations in the Mongol breast cancer patients of Russia.\n \n \n \n \n\n\n \n Gervas, P.; Denisov, E.; Kiselev, A.; Molokov, A.; Ivanova, A.; Choynzonov, E.; and Cherdyntseva, N.\n\n\n \n\n\n\n European Journal of Cancer, 138: S78. October 2020.\n Publisher: Elsevier\n\n\n\n
\n\n\n\n \n \n $\"Non-BRCA$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 4 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{gervas_non-brca_2020,\n\ttitle = {Non-{BRCA} hereditary gene mutations in the {Mongol} breast cancer patients of {Russia}},\n\tvolume = {138},\n\tissn = {0959-8049, 1879-0852},\n\turl = {https://www.ejcancer.com/article/S0959-8049(20)30739-5/abstract},\n\tdoi = {10.1016/S0959-8049(20)30739-5},\n\tabstract = {Background: Breast cancer (BC) is the most prevalent female malignancy worldwide.\nIn Russians, who were descended primarily from Slavic ancestors (newcomers), a strong\nfounder effect was observed for the BRCA1 5382insC allele, which account up to 90\\%\nof all known BC-associated mutations in this population. To date, despite a significant\nburden of cancer and limited access to genetic cancer risk assessments there are a\nlimited number of reports on the inherited gene mutations associated with BC among\nethnic groups in Russia.},\n\tlanguage = {English},\n\turldate = {2020-10-12},\n\tjournal = {European Journal of Cancer},\n\tauthor = {Gervas, P. and Denisov, E. and Kiselev, A. and Molokov, A. and Ivanova, A. and Choynzonov, E. and Cherdyntseva, N.},\n\tmonth = oct,\n\tyear = {2020},\n\tnote = {Publisher: Elsevier},\n\tkeywords = {HCS, SOPHiA DDM},\n\tpages = {S78},\n}\n\n

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\n \n\n \n \n \n \n \n \n Reliability and reproducibility among different platforms for tumour BRCA testing in ovarian cancer: a study of the Italian NGS Network.\n \n \n \n \n\n\n \n Fumagalli, C.; Guerini-Rocco, E.; Buttitta, F.; Iapicca, P.; You, W.; Mauri, M.; Felicioni, L.; Troncone, G.; Malapelle, U.; Scarpa, A.; Zamboni, G.; Calistri, D.; Barberis, M.; and Marchetti, A.\n\n\n \n\n\n\n Journal of Clinical Pathology. October 2020.\n Publisher: BMJ Publishing Group Section: Short report\n\n\n\n
\n\n\n\n \n \n $\"Reliability$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{fumagalli_reliability_2020,\n\ttitle = {Reliability and reproducibility among different platforms for tumour {BRCA} testing in ovarian cancer: a study of the {Italian} {NGS} {Network}},\n\tcopyright = {© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.},\n\tissn = {0021-9746, 1472-4146},\n\tshorttitle = {Reliability and reproducibility among different platforms for tumour {BRCA} testing in ovarian cancer},\n\turl = {https://jcp.bmj.com/content/early/2020/10/05/jclinpath-2020-206800},\n\tdoi = {10.1136/jclinpath-2020-206800},\n\tabstract = {Introduction BRCA tumour testing is a crucial tool for personalised therapy of patients with ovarian cancer. Since different next-generation sequencing (NGS) platforms and BRCA panels are available, the NGS Italian Network proposed to assess the robustness of different technologies.\nMethods Six centres, using four different technologies, provided raw data of 284 cases, including 75 cases with pathogenic/likely pathogenic variants, for a revision blindly performed by an external bioinformatic platform.\nResults The third-party revision assessed that all the 284 raw data reached good quality parameters. The variant calling analysis confirmed all the 75 pathogenic/likely pathogenic variants, including challenging variants, achieving a concordance rate of 100\\% regardless of the panel, instrument and bioinformatic pipeline adopted. No additional variants were identified in the reanalysis of a subset of 41 cases.\nConclusions BRCA tumour testing performed with different technologies in different centres, may achieve the realibility and reproducibility required for clinical diagnostic procedures.},\n\tlanguage = {en},\n\turldate = {2020-10-07},\n\tjournal = {Journal of Clinical Pathology},\n\tauthor = {Fumagalli, Caterina and Guerini-Rocco, Elena and Buttitta, Fiamma and Iapicca, Pierluigi and You, Wenqi and Mauri, Michela and Felicioni, Lara and Troncone, Giancarlo and Malapelle, Umberto and Scarpa, Aldo and Zamboni, Giuseppe and Calistri, Daniele and Barberis, Massimo and Marchetti, Antonio},\n\tmonth = oct,\n\tyear = {2020},\n\tpmid = {33020174},\n\tnote = {Publisher: BMJ Publishing Group\nSection: Short report},\n\tkeywords = {BRCA-related cancer, BRCA1/2, Benchmark, SOPHiA DDM, molecular, molecular biology, ovarian neoplasms, pathology},\n}\n\n

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\n \n\n \n \n \n \n \n \n Evaluation of 3 molecular-based assays for microsatellite instability detection in formalin-fixed tissues of patients with endometrial and colorectal cancers.\n \n \n \n \n\n\n \n Gilson, P.; Levy, J.; Rouyer, M.; Demange, J.; Husson, M.; Bonnet, C.; Salleron, J.; Leroux, A.; Merlin, J.; and Harlé, A.\n\n\n \n\n\n\n Scientific Reports, 10(1): 16386. October 2020.\n Number: 1 Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"Evaluation$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{gilson_evaluation_2020,\n\ttitle = {Evaluation of 3 molecular-based assays for microsatellite instability detection in formalin-fixed tissues of patients with endometrial and colorectal cancers},\n\tvolume = {10},\n\tcopyright = {2020 The Author(s)},\n\tissn = {2045-2322},\n\turl = {https://www.nature.com/articles/s41598-020-73421-5},\n\tdoi = {10.1038/s41598-020-73421-5},\n\tabstract = {Microsatellite instability (MSI) status is routinely assessed in patients with colorectal and endometrial cancers as it contributes to Lynch syndrome initial screening, tumour prognosis and selecting patients for immunotherapy. Currently, standard reference methods recommended for MSI/dMMR (deficient MisMatch Repair) testing consist of immunohistochemistry and pentaplex PCR-based assays, however, novel molecular-based techniques are emerging. Here, we aimed to evaluate the performance of a custom capture-based NGS method and the Bio-Rad ddPCR and Idylla approaches for the determination of MSI status for theranostic purposes in 30 formalin-fixed paraffin embedded (FFPE) tissue samples from patients with endometrial (n = 15) and colorectal (n = 15) cancers. All samples were previously characterised using IHC and Promega MSI Analysis System and these assays set as golden standard. Overall agreement, sensitivity and specificity of our custom-built NGS panel were 93.30\\%, 93.75\\% and 92.86\\% respectively. Overall agreement, sensitivity and specificity were 100\\% with the Idylla MSI system. The Bio-Rad ddPCR MSI assay showed a 100\\% concordance, sensitivity and specificity. The custom capture-based NGS, Bio-Rad ddPCR and Idylla approaches represent viable and complementary options to IHC and Promega MSI Analysis System for the detection of MSI. Bio-Rad ddPCR and Idylla MSI assays accounts for easy and fast screening assays while the NGS approach offers the advantages to simultaneously detect MSI and clinically relevant genomic alterations.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2020-10-06},\n\tjournal = {Scientific Reports},\n\tauthor = {Gilson, Pauline and Levy, Julien and Rouyer, Marie and Demange, Jessica and Husson, Marie and Bonnet, Céline and Salleron, Julia and Leroux, Agnès and Merlin, Jean-Louis and Harlé, Alexandre},\n\tmonth = oct,\n\tyear = {2020},\n\tnote = {Number: 1\nPublisher: Nature Publishing Group},\n\tkeywords = {MSI, MicroSatellite Instability analysis (MSI), SOPHiA DDM, STS},\n\tpages = {16386},\n}\n\n

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\n \n\n \n \n \n \n \n Artificial Intelligence Fuelling the Health Care.\n \n \n \n\n\n \n Jindal, S.; Sharma, A.; Joshi, A.; and Gupta, M.\n\n\n \n\n\n\n In Marriwala, N.; Tripathi, C. C.; Kumar, D.; and Jain, S., editor(s), Mobile Radio Communications and 5G Networks, of Lecture Notes in Networks and Systems, pages 501–507, Singapore, September 2020. Springer\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@inproceedings{jindal_artificial_2020,\n\taddress = {Singapore},\n\tseries = {Lecture {Notes} in {Networks} and {Systems}},\n\ttitle = {Artificial {Intelligence} {Fuelling} the {Health} {Care}},\n\tisbn = {9789811571305},\n\tdoi = {10.1007/978-981-15-7130-5_40},\n\tabstract = {Artificial intelligence (AI) is defined as the power of intellectual human mind that designs an intelligent working system which proves in terms of computational power designed by the human intelligence. AI is designed in such a way that it commences to simulate the thought of brain, their thinking pattern, analysing approach and way of computing the problem. AI is one of the most notable fields in the current scenario of Fourth Industrial Revolution. AI is not a concept which finds its application in single field, but it can be used in many domains such as health care, medicines, evolutionary computation, security purposes, diagnosis and evaluation, image classification, accounting databases, transportation and smart cities. AI explores new routes of computation and follows heuristic approaches in order to solve biological problems. The present paper defines applications and current role of AI in health care and how it relates in studies including diagnosis process, image classification for diagnostic sciences, measuring the tendency of congestive heart failure, genetic analysis, drug discovery and much more. New techniques and methods are always a great tool to learn more, analyse more, as well as extract some useful information. Finally, a broad perception of this emerging topic is mentioned here to prove the positive role of AI with biotechnology and health care.},\n\tlanguage = {en},\n\tbooktitle = {Mobile {Radio} {Communications} and {5G} {Networks}},\n\tpublisher = {Springer},\n\tauthor = {Jindal, Sahil and Sharma, Archit and Joshi, Akanksha and Gupta, Muskan},\n\teditor = {Marriwala, Nikhil and Tripathi, C. C. and Kumar, Dinesh and Jain, Shruti},\n\tmonth = sep,\n\tyear = {2020},\n\tkeywords = {Artificial intelligence, Biotechnology, Diagnosis and health care},\n\tpages = {501--507},\n}\n\n

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\n \n\n \n \n \n \n \n Generalized Additive Models for the Detection of Copy Number Variations (CNVs) Using Multi-gene Panel Sequencing Data.\n \n \n \n\n\n \n Ernst, C.; Schmutzler, R. K.; and Hahnen, E.\n\n\n \n\n\n\n In Imaizumi, T.; Okada, A.; Miyamoto, S.; Sakaori, F.; Yamamoto, Y.; and Vichi, M., editor(s), Advanced Studies in Classification and Data Science, of Studies in Classification, Data Analysis, and Knowledge Organization, pages 199–213, Singapore, September 2020. Springer\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@inproceedings{ernst_generalized_2020,\n\taddress = {Singapore},\n\tseries = {Studies in {Classification}, {Data} {Analysis}, and {Knowledge} {Organization}},\n\ttitle = {Generalized {Additive} {Models} for the {Detection} of {Copy} {Number} {Variations} ({CNVs}) {Using} {Multi}-gene {Panel} {Sequencing} {Data}},\n\tisbn = {9789811533112},\n\tdoi = {10.1007/978-981-15-3311-2_16},\n\tabstract = {We present a generalized additive models framework for the detection of germline chromosomal copy number variations from multi-gene panel sequencing data. Mean read abundances along a gene panel target are modelled as a product of two smooth functions, namely a generic background function that contributes to all samples under consideration and a sample-specific smooth function which is used for final copy number variation calling. We validated our approach on 442 germline samples that were sequenced on a customized diagnostic gene panel comprising exons of 49 genes and found that the proposed method outperforms existing approaches both in sensitivity and specificity.},\n\tlanguage = {en},\n\tbooktitle = {Advanced {Studies} in {Classification} and {Data} {Science}},\n\tpublisher = {Springer},\n\tauthor = {Ernst, Corinna and Schmutzler, Rita K. and Hahnen, Eric},\n\teditor = {Imaizumi, Tadashi and Okada, Akinori and Miyamoto, Sadaaki and Sakaori, Fumitake and Yamamoto, Yoshiro and Vichi, Maurizio},\n\tmonth = sep,\n\tyear = {2020},\n\tkeywords = {BRCA1, CNV, SOPHiA DDM},\n\tpages = {199--213},\n}\n\n

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\n \n\n \n \n \n \n \n \n First Infertile Case with CSTF2TGene Mutation.\n \n \n \n \n\n\n \n Gorukmez, O.; and Gorukmez, O.\n\n\n \n\n\n\n Molecular Syndromology,1–4. September 2020.\n Publisher: Karger Publishers\n\n\n\n
\n\n\n\n \n \n $\"First$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{gorukmez_first_2020,\n\ttitle = {First {Infertile} {Case} with {CSTF2TGene} {Mutation}},\n\tissn = {1661-8769, 1661-8777},\n\turl = {https://www.karger.com/Article/FullText/509686},\n\tdoi = {10.1159/000509686},\n\tabstract = {Male infertility is multifactorial and presents with heterogeneous phenotypic features. Genetic factors are responsible for up to 15\\% of the male infertility cases. Loss of the \\textit{Cstf2t} gene in male mice results in infertility. No disease-associated mutations have been described for this gene in infertile men. Here, we report a patient diagnosed with infertility in whom a homozygous nonsense mutation in the \\textit{CSTF2T} gene was detected by clinical exome sequencing. This case is the first description of an infertile patient who has a homozygous \\textit{CSTF2T} mutation.},\n\tlanguage = {english},\n\turldate = {2020-09-22},\n\tjournal = {Molecular Syndromology},\n\tauthor = {Gorukmez, Ozlem and Gorukmez, Orhan},\n\tmonth = sep,\n\tyear = {2020},\n\tnote = {Publisher: Karger Publishers},\n\tkeywords = {Clinical Exome, Exome, Large panel, SOPHiA DDM},\n\tpages = {1--4},\n}\n\n

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\n \n\n \n \n \n \n \n \n Polycythemia Vera Evolution to Chronic Myelomocytic Leukemia: The Prognostic Value of Next Generation Sequencing.\n \n \n \n \n\n\n \n Huguet, M.; Zamora, L.; Granada, I.; Orna, E.; Mesa, A.; Tapia, G.; Sorigué, M.; Fernández-Sanmartín, M. A.; Xicoy, B.; and Navarro, J.\n\n\n \n\n\n\n HemaSphere, 4(5): e466. September 2020.\n \n\n\n\n
\n\n\n\n \n \n $\"Polycythemia$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{huguet_polycythemia_2020,\n\ttitle = {Polycythemia {Vera} {Evolution} to {Chronic} {Myelomocytic} {Leukemia}: {The} {Prognostic} {Value} of {Next} {Generation} {Sequencing}},\n\tvolume = {4},\n\tissn = {2572-9241},\n\tshorttitle = {Polycythemia {Vera} {Evolution} to {Chronic} {Myelomocytic} {Leukemia}},\n\turl = {https://journals.lww.com/hemasphere/Fulltext/2020/10000/Polycythemia_Vera_Evolution_to_Chronic.6.aspx},\n\tdoi = {10.1097/HS9.0000000000000466},\n\tabstract = {An abstract is unavailable.},\n\tlanguage = {en-US},\n\tnumber = {5},\n\turldate = {2020-09-17},\n\tjournal = {HemaSphere},\n\tauthor = {Huguet, Maria and Zamora, Lurdes and Granada, Isabel and Orna, Elisa and Mesa, Alba and Tapia, Gustavo and Sorigué, Marc and Fernández-Sanmartín, Marco Antonio and Xicoy, Blanca and Navarro, José-Tomás},\n\tmonth = sep,\n\tyear = {2020},\n\tkeywords = {MYS, Myeloid, Myeloproliferative Neoplasms},\n\tpages = {e466},\n}\n\n

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\n \n\n \n \n \n \n \n \n Recessive MYH3 variants cause “Contractures, pterygia, and variable skeletal fusions syndrome 1B” mimicking Escobar variant multiple pterygium syndrome.\n \n \n \n \n\n\n \n Hakonen, A. H.; Lehtonen, J.; Kivirikko, S.; Keski‐Filppula, R.; Moilanen, J.; Kivisaari, R.; Almusa, H.; Jakkula, E.; Saarela, J.; Avela, K.; and Aittomäki, K.\n\n\n \n\n\n\n American Journal of Medical Genetics Part A, n/a(n/a). September 2020.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajmg.a.61836\n\n\n\n
\n\n\n\n \n \n $\"Recessive$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{hakonen_recessive_2020,\n\ttitle = {Recessive {MYH3} variants cause “{Contractures}, pterygia, and variable skeletal fusions syndrome {1B}” mimicking {Escobar} variant multiple pterygium syndrome},\n\tvolume = {n/a},\n\tcopyright = {© 2020 Wiley Periodicals LLC},\n\tissn = {1552-4833},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.61836},\n\tdoi = {10.1002/ajmg.a.61836},\n\tabstract = {The multiple pterygium syndromes (MPS) are rare disorders with disease severity ranging from lethal to milder forms. The nonlethal Escobar variant MPS (EVMPS) is characterized by multiple pterygia and arthrogryposis, as well as various additional features including congenital anomalies. The genetic etiology of EVMPS is heterogeneous and the diagnosis has been based either on the detection of pathogenic CHRNG variants ( 23\\% of patients), or suggestive clinical features. We describe four patients with a clinical suspicion of EVMPS who manifested with multiple pterygia, mild flexion contractures of several joints, and vertebral anomalies. We revealed recessively inherited MYH3 variants as the underlying cause in all patients: two novel variants, c.1053C{\\textgreater}G, p.(Tyr351Ter) and c.3102+5G{\\textgreater}C, as compound heterozygous with the hypomorphic MYH3 variant c.-9+1G{\\textgreater}A. Recessive MYH3 variants have been previously associated with spondylocarpotarsal synostosis syndrome. Our findings now highlight multiple pterygia as an important feature in patients with recessive MYH3 variants. Based on all patients with recessive MYH3 variants reported up to date, we consider that this disease entity should be designated as “Contractures, pterygia, and variable skeletal fusions syndrome 1B,” as recently suggested by OMIM. Our findings underline the importance of analyzing MYH3 in the differential diagnosis of EVMPS, particularly as the hypomorphic MYH3 variant might remain undetected by routine exome sequencing.},\n\tlanguage = {en},\n\tnumber = {n/a},\n\turldate = {2020-09-15},\n\tjournal = {American Journal of Medical Genetics Part A},\n\tauthor = {Hakonen, Anna H. and Lehtonen, Johanna and Kivirikko, Sirpa and Keski‐Filppula, Riikka and Moilanen, Jukka and Kivisaari, Reetta and Almusa, Henrikki and Jakkula, Eveliina and Saarela, Janna and Avela, Kristiina and Aittomäki, Kristiina},\n\tmonth = sep,\n\tyear = {2020},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajmg.a.61836},\n\tkeywords = {CPSKF1B, Contractures, Escobar variant of multiple pterygium syndrome, MYH3, and variable skeletal fusions syndrome 1B”, arthrogryposis, pterygia, spondylocarpotarsal synostosis syndrome},\n}\n\n

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\n \n\n \n \n \n \n \n \n iPSC Modeling of RBM20-Deficient DCM Identifies Upregulation of RBM20 as a Therapeutic Strategy.\n \n \n \n \n\n\n \n Briganti, F.; Sun, H.; Wei, W.; Wu, J.; Zhu, C.; Liss, M.; Karakikes, I.; Rego, S.; Cipriano, A.; Snyder, M.; Meder, B.; Xu, Z.; Millat, G.; Gotthardt, M.; Mercola, M.; and Steinmetz, L. M.\n\n\n \n\n\n\n Cell Reports, 32(10): 108117. September 2020.\n \n\n\n\n
\n\n\n\n \n \n $\"iPSC$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{briganti_ipsc_2020,\n\ttitle = {{iPSC} {Modeling} of {RBM20}-{Deficient} {DCM} {Identifies} {Upregulation} of {RBM20} as a {Therapeutic} {Strategy}},\n\tvolume = {32},\n\tissn = {2211-1247},\n\turl = {http://www.sciencedirect.com/science/article/pii/S2211124720311062},\n\tdoi = {10.1016/j.celrep.2020.108117},\n\tabstract = {Recent advances in induced pluripotent stem cell (iPSC) technology and directed differentiation of iPSCs into cardiomyocytes (iPSC-CMs) make it possible to model genetic heart disease in vitro. We apply CRISPR/Cas9 genome editing technology to introduce three RBM20 mutations in iPSCs and differentiate them into iPSC-CMs to establish an in vitro model of RBM20 mutant dilated cardiomyopathy (DCM). In iPSC-CMs harboring a known causal RBM20 variant, the splicing of RBM20 target genes, calcium handling, and contractility are impaired consistent with the disease manifestation in patients. A variant (Pro633Leu) identified by exome sequencing of patient genomes displays the same disease phenotypes, thus establishing this variant as disease causing. We find that all-trans retinoic acid upregulates RBM20 expression and reverts the splicing, calcium handling, and contractility defects in iPSC-CMs with different causal RBM20 mutations. These results suggest that pharmacological upregulation of RBM20 expression is a promising therapeutic strategy for DCM patients with a heterozygous mutation in RBM20.},\n\tlanguage = {en},\n\tnumber = {10},\n\turldate = {2020-09-14},\n\tjournal = {Cell Reports},\n\tauthor = {Briganti, Francesca and Sun, Han and Wei, Wu and Wu, Jingyan and Zhu, Chenchen and Liss, Martin and Karakikes, Ioannis and Rego, Shannon and Cipriano, Andrea and Snyder, Michael and Meder, Benjamin and Xu, Zhenyu and Millat, Gilles and Gotthardt, Michael and Mercola, Mark and Steinmetz, Lars M.},\n\tmonth = sep,\n\tyear = {2020},\n\tkeywords = {DCM, RBM20, alternative splicing, cardiomyocytes, disease modeling, genome editing, iPSC, precision medicine},\n\tpages = {108117},\n}\n\n

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\n \n\n \n \n \n \n \n \n Contribution of BRCA1 and BRCA2 germline mutations to early onset breast cancer: a series from north of Morocco.\n \n \n \n \n\n\n \n Bakkach, J.; Mansouri, M.; Derkaoui, T.; Loudiyi, A.; El Fahime, E.; Barakat, A.; Ghailani Nourouti, N.; Martinez De Villarreal, J.; Cortijo Bringas, C.; and Bennani Mechita, M.\n\n\n \n\n\n\n BMC Cancer, 20(1): 859. September 2020.\n \n\n\n\n
\n\n\n\n \n \n $\"Contribution$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{bakkach_contribution_2020,\n\ttitle = {Contribution of {BRCA1} and {BRCA2} germline mutations to early onset breast cancer: a series from north of {Morocco}},\n\tvolume = {20},\n\tissn = {1471-2407},\n\tshorttitle = {Contribution of {BRCA1} and {BRCA2} germline mutations to early onset breast cancer},\n\turl = {https://doi.org/10.1186/s12885-020-07352-9},\n\tdoi = {10.1186/s12885-020-07352-9},\n\tabstract = {To date, the contribution of BRCA1/2 mutations in Moroccan early onset breast cancer patients remains unknown. Here we assess these genetic alterations for the first time in a cohort from North of Morocco.},\n\tnumber = {1},\n\turldate = {2020-09-14},\n\tjournal = {BMC Cancer},\n\tauthor = {Bakkach, Joaira and Mansouri, Mohamed and Derkaoui, Touria and Loudiyi, Ali and El Fahime, ElMostafa and Barakat, Amina and Ghailani Nourouti, Naima and Martinez De Villarreal, Jaime and Cortijo Bringas, Carlos and Bennani Mechita, Mohcine},\n\tmonth = sep,\n\tyear = {2020},\n\tkeywords = {BRCA-related cancer, BRCA1, BRCA2, SOPHiA DDM},\n\tpages = {859},\n}\n\n

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\n \n\n \n \n \n \n \n \n The role of genetic mutations in intrahepatic cholestasis of pregnancy.\n \n \n \n \n\n\n \n Aydın, G. A.; Özgen, G.; and Görükmez, O.\n\n\n \n\n\n\n Taiwanese Journal of Obstetrics and Gynecology, 59(5): 706–710. September 2020.\n \n\n\n\n
\n\n\n\n \n \n $\"The$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{aydin_role_2020,\n\ttitle = {The role of genetic mutations in intrahepatic cholestasis of pregnancy},\n\tvolume = {59},\n\tissn = {1028-4559},\n\turl = {http://www.sciencedirect.com/science/article/pii/S1028455920301686},\n\tdoi = {10.1016/j.tjog.2020.07.014},\n\tabstract = {Objective\nIntrahepatic cholestasis of pregnancy (ICP) is a liver disorder of pregnancy characterized by pruritus, elevated liver enzymes and fasting serum bile acids. Genetic predisposition has been suggested to play a role in its etiology and mutations in the ATP8B1(OMIM ∗602397) (FIC1), ABCB11(OMIM ∗603201) (BSEP), and ABCB4(OMIM ∗171060) (MDR3) genes have been implicated. In the present study, we aimed to investigate the possible role of ATP8B1, ABCB11, and ABCB4 gene mutations in the patients with ICP.\nMaterials and methods\nA total of 25 patients who were diagnosed with ICP were included in the study. Genetic test results and mutation status of the patients as assessed by the next-generation sequencing technology were retrospectively retrieved from the hospital database.\nResults\nOf all patients, significant alterations in the ATP8B1 (n = 2), ABCB11 (n = 1), and ABCB4 (n = 7) genes were observed in 10 patients using the molecular analysis testing. All these alterations were heterozygous. Of these alterations, four were reported in the literature previously, while six were not. Using the in-silico parameters, there was a pathogenic alteration in the ABCB4 gene in one patient, while there was no clinically relevant alteration in the other gene mutations in the remaining nine patients.\nConclusion\nConsidering the fact that the alterations were compatible with clinical presentations of the ICP patients and the incidence of these mutations is low in the general population, we believe that our study results are clinically relevant. Further molecular genetic tests in ICP patients and functional studies supporting the results would shed light into the clinical importance of these alterations.},\n\tlanguage = {en},\n\tnumber = {5},\n\turldate = {2020-09-14},\n\tjournal = {Taiwanese Journal of Obstetrics and Gynecology},\n\tauthor = {Aydın, Gültekin Adanaş and Özgen, Gülten and Görükmez, Orhan},\n\tmonth = sep,\n\tyear = {2020},\n\tkeywords = {Intrahepatic cholestasis of pregnancy, Mutation, SOPHiA DDM},\n\tpages = {706--710},\n}\n\n

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\n \n\n \n \n \n \n \n \n A new splice-site mutation of SPINK5 gene in the Netherton syndrome with different clinical features: A case report.\n \n \n \n \n\n\n \n Erden, E.; Ceylan, A. C.; and Emre, S.\n\n\n \n\n\n\n Balkan Journal of Medical Genetics, 23(1): 91–94. August 2020.\n Publisher: Sciendo Section: Balkan Journal of Medical Genetics\n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{erden_new_2020,\n\ttitle = {A new splice-site mutation of {SPINK5} gene in the {Netherton} syndrome with different clinical features: {A} case report},\n\tvolume = {23},\n\tshorttitle = {A new splice-site mutation of {SPINK5} gene in the {Netherton} syndrome with different clinical features},\n\turl = {https://content.sciendo.com/view/journals/bjmg/23/1/article-p91.xml},\n\tdoi = {10.2478/bjmg-2020-0012},\n\tabstract = {{\\textless}section class="abstract"{\\textgreater}{\\textless}h2 class="abstractTitle text-title my-1" id="d505e2"{\\textgreater}Abstract{\\textless}/h2{\\textgreater}{\\textless}p{\\textgreater}Netherton syndrome (NS) is a rare genodermatosis characterized by the triad of ichthyosiform erythroderma, hair shaft abnormality and an atopic diathesis. We report a case of a 20-year-old male patient presented with pruritus, decreased sweat secretion and generalized erythema on his body. Netherton syndrome is caused by mutations in the {\\textless}em{\\textgreater}SPINK5{\\textless}/em{\\textgreater} gene that is a crucial role for epidermal barrier function in the skin. Different clinical and phenotypical features can occur based on various LEKTI-domains mutations. Diagnosis is made by the atopic story, hair shaft abnormality, cutaneous lesions and identification of the {\\textless}em{\\textgreater}SPINK5{\\textless}/em{\\textgreater} gene mutation. In our patient, we detected a new splice site mutation in the {\\textless}em{\\textgreater}SPINK5{\\textless}/em{\\textgreater} gene and pili annulati as hair abnormality. Affected patients are usually misdiagnosed because of cutaneous lesions such as atopic dermatitis. Therefore, each clinical finding should be evaluated together. We aimed to present a case with a new {\\textless}em{\\textgreater}SPINK5{\\textless}/em{\\textgreater} gene mutation and different clinical features in NS.{\\textless}/p{\\textgreater}{\\textless}/section{\\textgreater}},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2020-09-01},\n\tjournal = {Balkan Journal of Medical Genetics},\n\tauthor = {Erden, E. and Ceylan, A. C. and Emre, S.},\n\tmonth = aug,\n\tyear = {2020},\n\tnote = {Publisher: Sciendo\nSection: Balkan Journal of Medical Genetics},\n\tpages = {91--94},\n}\n\n

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\n \n\n \n \n \n \n \n \n Prognostic factors and follow-up parameters in patients with paroxysmal nocturnal hemoglobinuria (PNH): experience of the Austrian PNH network.\n \n \n \n \n\n\n \n Füreder, W.; Sperr, W. R.; Heibl, S.; Zebisch, A.; Pfeilstöcker, M.; Stefanzl, G.; Jäger, E.; Greiner, G.; Schwarzinger, I.; Kundi, M.; Keil, F.; Hoermann, G.; Bettelheim, P.; and Valent, P.\n\n\n \n\n\n\n Annals of Hematology. August 2020.\n \n\n\n\n
\n\n\n\n \n \n $\"Prognostic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{fureder_prognostic_2020,\n\ttitle = {Prognostic factors and follow-up parameters in patients with paroxysmal nocturnal hemoglobinuria ({PNH}): experience of the {Austrian} {PNH} network},\n\tissn = {1432-0584},\n\tshorttitle = {Prognostic factors and follow-up parameters in patients with paroxysmal nocturnal hemoglobinuria ({PNH})},\n\turl = {https://doi.org/10.1007/s00277-020-04214-z},\n\tdoi = {10.1007/s00277-020-04214-z},\n\tabstract = {Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disease characterized by a deregulated complement system, chronic Coombs-negative, intravascular hemolysis, and a variable clinical course with substantial risk to develop thromboembolic events. We analyzed diagnostic and prognostic parameters as well as clinical endpoints in 59 adult patients suffering from PNH in 5 hematology centers in Austria (observation period: 1978–2015). Median follow-up time was 5.6 years. The median clone size at diagnosis amounted to 55\\% and was higher in patients with classical PNH (81\\%) compared to patients with PNH associated with aplastic anemia (AA) or myelodysplastic syndromes (MDS) (50\\%). The clone size also correlated with lactate dehydrogenase (LDH) levels. In one patient, anemia improved spontaneously and disappeared with complete normalization of LDH after 16 years. Seventeen patients received therapy with eculizumab. The rate of thromboembolic events was higher in the pre-eculizumab era compared with eculizumab-treated patients but did not correlate with the presence of age-related clonal hematopoiesis or any other clinical or laboratory parameters. Peripheral blood colony-forming progenitor cell counts were lower in PNH patients compared with healthy controls. Only two patients with classical PNH developed MDS. Overall, 7/59 patients died after 0.5–32 years. Causes of death were acute pulmonary hypertension, Budd-Chiari syndrome, and septicemia. Overall survival (OS) was mainly influenced by age and was similar to OS measured in an age-matched healthy Austrian control cohort. Together, compared with previous times, the clinical course and OS in PNH are favorable, which may be due to better diagnosis, early recognition, and eculizumab therapy.},\n\tlanguage = {en},\n\turldate = {2020-09-01},\n\tjournal = {Annals of Hematology},\n\tauthor = {Füreder, Wolfgang and Sperr, W. R. and Heibl, S. and Zebisch, A. and Pfeilstöcker, M. and Stefanzl, G. and Jäger, E. and Greiner, G. and Schwarzinger, I. and Kundi, M. and Keil, F. and Hoermann, G. and Bettelheim, P. and Valent, P.},\n\tmonth = aug,\n\tyear = {2020},\n\tkeywords = {MYS, Myeloid, SOPHiA DDM},\n}\n\n

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\n \n\n \n \n \n \n \n \n Characterization of FLT3 -ITD mut acute myeloid leukemia: molecular profiling of leukemic precursor cells.\n \n \n \n \n\n\n \n Travaglini, S.; Angelini, D. F.; Alfonso, V.; Guerrera, G.; Lavorgna, S.; Divona, M.; Nardozza, A. M.; Consalvo, M. I.; Fabiani, E.; De Bardi, M.; Neri, B.; Forghieri, F.; Marchesi, F.; Paterno, G.; Cerretti, R.; Barragan, E.; Fiori, V.; Dominici, S.; Del Principe, M. I.; Venditti, A.; Battistini, L.; Arcese, W.; Lo-Coco, F.; Voso, M. T.; and Ottone, T.\n\n\n \n\n\n\n Blood Cancer Journal, 10(8): 1–11. August 2020.\n Number: 8 Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"Characterization$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{travaglini_characterization_2020,\n\ttitle = {Characterization of {FLT3} -{ITD} mut acute myeloid leukemia: molecular profiling of leukemic precursor cells},\n\tvolume = {10},\n\tcopyright = {2020 The Author(s)},\n\tissn = {2044-5385},\n\tshorttitle = {Characterization of {FLT3} -{ITD} mut acute myeloid leukemia},\n\turl = {https://www.nature.com/articles/s41408-020-00352-9},\n\tdoi = {10.1038/s41408-020-00352-9},\n\tabstract = {Acute myeloid leukemia (AML) with FLT3-ITD mutations (FLT3-ITDmut) remains a therapeutic challenge, with a still high relapse rate, despite targeted treatment with tyrosine kinase inhibitors. In this disease, the CD34/CD123/CD25/CD99+ leukemic precursor cells (LPCs) phenotype predicts for FLT3-ITD-positivity. The aim of this study was to characterize the distribution of FLT3-ITD mutation in different progenitor cell subsets to shed light on the subclonal architecture of FLT3-ITDmut AML. Using high-speed cell sorting, we sequentially purified LPCs and CD34+ progenitors in samples from patients with FLT3-ITDmut AML (n = 12). A higher FLT3-ITDmut load was observed within CD34/CD123/CD25/CD99+ LPCs, as compared to CD34+ progenitors (CD123+/−,CD25−,CD99low/−) (p = 0.0005) and mononuclear cells (MNCs) (p {\\textless} 0.0001). This was associated with significantly increased CD99 mean fluorescence intensity in LPCs. Significantly higher FLT3-ITDmut burden was also observed in LPCs of AML patients with a small FLT3-ITDmut clones at diagnosis. On the contrary, the mutation burden of other myeloid genes was similar in MNCs, highly purified LPCs and/or CD34+ progenitors. Treatment with an anti-CD99 mAb was cytotoxic on LPCs in two patients, whereas there was no effect on CD34+ cells from healthy donors. Our study shows that FLT3-ITD mutations occur early in LPCs, which represent the leukemic reservoir. CD99 may represent a new therapeutic target in FLT3-ITDmut AML.},\n\tlanguage = {en},\n\tnumber = {8},\n\turldate = {2020-08-29},\n\tjournal = {Blood Cancer Journal},\n\tauthor = {Travaglini, Serena and Angelini, Daniela Francesca and Alfonso, Valentina and Guerrera, Gisella and Lavorgna, Serena and Divona, Mariadomenica and Nardozza, Anna Maria and Consalvo, Maria Irno and Fabiani, Emiliano and De Bardi, Marco and Neri, Benedetta and Forghieri, Fabio and Marchesi, Francesco and Paterno, Giovangiacinto and Cerretti, Raffaella and Barragan, Eva and Fiori, Valentina and Dominici, Sabrina and Del Principe, Maria Ilaria and Venditti, Adriano and Battistini, Luca and Arcese, William and Lo-Coco, Francesco and Voso, Maria Teresa and Ottone, Tiziana},\n\tmonth = aug,\n\tyear = {2020},\n\tnote = {Number: 8\nPublisher: Nature Publishing Group},\n\tkeywords = {MYS, Myeloid},\n\tpages = {1--11},\n}\n\n

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\n \n\n \n \n \n \n \n \n Identification through exome sequencing of the first PMM2-CDG individual of Mexican mestizo origin.\n \n \n \n \n\n\n \n González-Domínguez, C. A.; Raya-Trigueros, A.; Manrique-Hernández, S.; González Jaimes, A.; Salinas-Marín, R.; Molina-Garay, C.; Carrillo-Sánchez, K.; Flores-Lagunes, L. L.; Jiménez-Olivares, M.; Dehesa-Caballero, C.; Alaez-Versón, C.; and Martínez-Duncker, I.\n\n\n \n\n\n\n Molecular Genetics and Metabolism Reports, 25: 100637. August 2020.\n \n\n\n\n
\n\n\n\n \n \n $\"Identification$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{gonzalez-dominguez_identification_2020,\n\ttitle = {Identification through exome sequencing of the first {PMM2}-{CDG} individual of {Mexican} mestizo origin},\n\tvolume = {25},\n\tissn = {2214-4269},\n\turl = {http://www.sciencedirect.com/science/article/pii/S2214426920300835},\n\tdoi = {10.1016/j.ymgmr.2020.100637},\n\tabstract = {Congenital Disorders of Glycosylation (CDG) are scarcely reported from Latin America. We here report on a Mexican mestizo with a multi-systemic syndrome including neurological involvement and a type I transferrin (Tf) isoelectric focusing (IEF) pattern. Clinical exome sequencing (CES) showed known compound missense variants in PMM2 c.422G {\\textgreater} A (p.R141H) and c.395 T {\\textgreater} C (p.I132T), coding for the phosphomanomutase 2 (PMM2). PMM2 catalyzes the conversion of mannose-6-P to mannose-1-P required for the synthesis of GDP-Man and Dol-P-Man, donor substrates for glycosylation reactions. This is the third reported Mexican CDG patient and the first with PMM2-CDG. PMM2 has been recently identified as one of the top 10 genes carrying pathogenic variants in a Mexican population cohort.},\n\tlanguage = {en},\n\turldate = {2020-08-27},\n\tjournal = {Molecular Genetics and Metabolism Reports},\n\tauthor = {González-Domínguez, C. A. and Raya-Trigueros, A. and Manrique-Hernández, S. and González Jaimes, A. and Salinas-Marín, R. and Molina-Garay, C. and Carrillo-Sánchez, K. and Flores-Lagunes, L. L. and Jiménez-Olivares, M. and Dehesa-Caballero, C. and Alaez-Versón, C. and Martínez-Duncker, I.},\n\tmonth = aug,\n\tyear = {2020},\n\tkeywords = {CDG, Clinical Exome, Exome, Glycosylation, Metabolism, PMM2, SOPHiA DDM},\n\tpages = {100637},\n}\n\n

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\n \n\n \n \n \n \n \n \n Segregation analysis of the BRCA2 c.9227G\\textgreaterT variant in multiple families suggests a pathogenic role in breast and ovarian cancer predisposition.\n \n \n \n \n\n\n \n Agata, S.; Tognazzo, S.; Alducci, E.; Matricardi, L.; Moserle, L.; Barana, D.; and Montagna, M.\n\n\n \n\n\n\n Scientific Reports, 10(1): 13987. August 2020.\n Number: 1 Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"Segregation$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{agata_segregation_2020,\n\ttitle = {Segregation analysis of the {BRCA2} c.{9227G}{\\textgreater}{T} variant in multiple families suggests a pathogenic role in breast and ovarian cancer predisposition},\n\tvolume = {10},\n\tcopyright = {2020 The Author(s)},\n\tissn = {2045-2322},\n\turl = {https://www.nature.com/articles/s41598-020-70729-0},\n\tdoi = {10.1038/s41598-020-70729-0},\n\tabstract = {Classification of variants in the BRCA1 and BRCA2 genes has a major impact on the clinical management of subjects at high risk for breast and ovarian cancer. The identification of a pathogenic variant allows for early detection/prevention strategies in healthy carriers as well as targeted treatments in patients affected by BRCA-associated tumors. The BRCA2 c.9227G{\\textgreater}T p.(Gly3076Val) variant recurs in families from Northeast Italy and is rarely reported in international databases. This variant substitutes the evolutionary invariant glycine 3076 with a valine in the DNA binding domain of the BRCA2 protein, thus suggesting a high probability of pathogenicity. We analysed clinical and genealogic data of carriers from 15 breast/ovarian cancer families in whom no other pathogenic variants were detected. The variant was shown to co-segregate with breast and ovarian cancer in the most informative families. Combined segregation data led to a likelihood ratio of 81,527:1 of pathogenicity vs. neutrality. We conclude that c.9227G{\\textgreater}T is a BRCA2 pathogenic variant that recurs in Northeast Italy. It can now be safely used for the predictive testing of healthy family members to guide preventive surgery and/or early tumor detection strategies, as well as for PARP inhibitors treatments in patients with BRCA2-associated tumors.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2020-08-27},\n\tjournal = {Scientific Reports},\n\tauthor = {Agata, Simona and Tognazzo, Silvia and Alducci, Elisa and Matricardi, Laura and Moserle, Lidia and Barana, Daniela and Montagna, Marco},\n\tmonth = aug,\n\tyear = {2020},\n\tnote = {Number: 1\nPublisher: Nature Publishing Group},\n\tkeywords = {CNV, SOPHiA DDM},\n\tpages = {13987},\n}\n\n

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\n \n\n \n \n \n \n \n \n Kevetrin induces apoptosis in TP53 wild‑type and mutant acute myeloid leukemia cells.\n \n \n \n \n\n\n \n Napolitano, R.; De Matteis, S.; Carloni, S.; Bruno, S.; Abbati, G.; Capelli, L.; Ghetti, M.; Bochicchio, M. T.; Liverani, C.; Mercatali, L.; Calistri, D.; Cuneo, A.; Menon, K.; Musuraca, G.; Martinelli, G.; and Simonetti, G.\n\n\n \n\n\n\n Oncology Reports, 44(4): 1561–1573. August 2020.\n Publisher: Spandidos Publications\n\n\n\n
\n\n\n\n \n \n $\"Kevetrin$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n

@article{napolitano_kevetrin_2020,\n\ttitle = {Kevetrin induces apoptosis in {TP53} wild‑type and mutant acute myeloid leukemia cells},\n\tvolume = {44},\n\tissn = {1021-335X},\n\turl = {http://www.spandidos-publications.com/10.3892/or.2020.7730/abstract},\n\tdoi = {10.3892/or.2020.7730},\n\tnumber = {4},\n\turldate = {2020-08-18},\n\tjournal = {Oncology Reports},\n\tauthor = {Napolitano, Roberta and De Matteis, Serena and Carloni, Silvia and Bruno, Samantha and Abbati, Giulia and Capelli, Laura and Ghetti, Martina and Bochicchio, Maria Teresa and Liverani, Chiara and Mercatali, Laura and Calistri, Daniele and Cuneo, Antonio and Menon, Krishna and Musuraca, Gerardo and Martinelli, Giovanni and Simonetti, Giorgia},\n\tmonth = aug,\n\tyear = {2020},\n\tnote = {Publisher: Spandidos Publications},\n\tkeywords = {MYS, Myeloid},\n\tpages = {1561--1573},\n}\n\n

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\n \n\n \n \n \n \n \n \n Novel Somatic Genetic Variants as Predictors of Resistance to EGFR-Targeted Therapies in Metastatic Colorectal Cancer Patients.\n \n \n \n \n\n\n \n Riera, P.; Rodríguez-Santiago, B.; Lasa, A.; Gonzalez-Quereda, L.; Martín, B.; Salazar, J.; Sebio, A.; Virgili, A. C.; Minguillón, J.; Camps, C.; Surrallés, J.; and Páez, D.\n\n\n \n\n\n\n Cancers, 12(8): 2245. August 2020.\n Number: 8 Publisher: Multidisciplinary Digital Publishing Institute\n\n\n\n
\n\n\n\n \n \n $\"Novel$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{riera_novel_2020,\n\ttitle = {Novel {Somatic} {Genetic} {Variants} as {Predictors} of {Resistance} to {EGFR}-{Targeted} {Therapies} in {Metastatic} {Colorectal} {Cancer} {Patients}},\n\tvolume = {12},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\turl = {https://www.mdpi.com/2072-6694/12/8/2245},\n\tdoi = {10.3390/cancers12082245},\n\tabstract = {Background: About 40\\% of RAS/BRAF wild-type metastatic colorectal cancer (mCRC) patients undergoing anti-EGFR-based therapy have poor outcomes. Treatment failure is not only associated with poorer prognosis but higher healthcare costs. Our aim was to identify novel somatic genetic variants in the primary tumor and assess their effect on anti-EGFR response. Patients and Methods: Tumor (somatic) and blood (germline) DNA samples were obtained from two well-defined cohorts of mCRC patients, those sensitive and those resistant to EGFR blockade. Genetic variant screening of 43 EGFR-related genes was performed using targeted next-generation sequencing (NGS). Relevant clinical data were collected through chart review to assess genetic results. Results: Among 61 patients, 38 were sensitive and 23 were resistant to treatment. We identified eight somatic variants that predicted non-response. Three were located in insulin-related genes (I668N and E1218K in IGF1R, T1156M in IRS2) and three in genes belonging to the LRIG family (T152T in LRIG1, S697L in LRIG2 and V812M in LRIG3). The remaining two variants were found in NRAS (G115Efs*46) and PDGFRA (T301T). We did not identify any somatic variants related to good response. Conclusions: This study provides evidence that novel somatic genetic variants along the EGFR-triggered pathway could modulate the response to anti-EGFR drugs in mCRC patients. It also highlights the influence of insulin-related genes and LRIG genes on anti-EGFR efficacy. Our findings could help characterize patients who are resistant to anti-EGFR blockade despite harboring RAS/BRAF wild-type tumors.},\n\tlanguage = {en},\n\tnumber = {8},\n\turldate = {2020-08-18},\n\tjournal = {Cancers},\n\tauthor = {Riera, Pau and Rodríguez-Santiago, Benjamín and Lasa, Adriana and Gonzalez-Quereda, Lidia and Martín, Berta and Salazar, Juliana and Sebio, Ana and Virgili, Anna C. and Minguillón, Jordi and Camps, Cristina and Surrallés, Jordi and Páez, David},\n\tmonth = aug,\n\tyear = {2020},\n\tnote = {Number: 8\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tkeywords = {Alamut, SOPHiA DDM, anti-EGFR monoclonal antibodies, case-control study, colorectal cancer, genetic variants, predictive biomarkers},\n\tpages = {2245},\n}\n\n

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\n \n\n \n \n \n \n \n Two patients with glutaric aciduria type 3: a novel mutation and brain magnetic resonance imaging findings.\n \n \n \n\n\n \n Dorum, S.; Havalı, C.; Görükmez, Ö.; and Görükmez, O.\n\n\n \n\n\n\n The Turkish Journal of Pediatrics, 62(4): 657–662. August 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{dorum_two_2020,\n\ttitle = {Two patients with glutaric aciduria type 3: a novel mutation and brain magnetic resonance imaging findings},\n\tvolume = {62},\n\tissn = {0041-4301},\n\tshorttitle = {Two patients with glutaric aciduria type 3},\n\tdoi = {10.24953/turkjped.2020.04.017},\n\tabstract = {BACKGROUND: Glutaric Aciduria Type 3 (GA-3) is a rare metabolic disease which is inherited autosomal recessively and characterized by isolated glutaric acid excretion. To date, a limited number of cases have been reported in the literature. We present two patients with GA3 who were diagnosed with the isolated increased level of glutaric acid in urine.\nCASE: Glutaric aciduria type 1 and type 2 were excluded by genetic analysis and other laboratory and clinical findings. One of our patients had a homozygous mutation p.Arg322Trp (c.964C {\\textgreater} T) of SUGCT (NM\\_001193311) gene. To the best of our knowledge this mutation has not been reported in the literature previously. Symmetrical periventricular and deep cerebral white matter abnormalities were detected on his brain magnetic resonance imaging (MRI).\nCONCLUSION: We present two patients with GA-3 and a novel mutation in the SUGCT gene. Our findings expand the spectrum of causative mutations and clinical findings in GA-3.},\n\tlanguage = {eng},\n\tnumber = {4},\n\tjournal = {The Turkish Journal of Pediatrics},\n\tauthor = {Dorum, Sevil and Havalı, Cengiz and Görükmez, Özlem and Görükmez, Orhan},\n\tmonth = aug,\n\tyear = {2020},\n\tpmid = {32779420},\n\tkeywords = {SUGCT gene, brain magnetic resonance imaging, glutaric aciduria type 3, novel mutation},\n\tpages = {657--662},\n}\n\n

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\n \n\n \n \n \n \n \n \n Molecular profiling and risk classification of patients with myeloproliferative neoplasms and splanchnic vein thromboses.\n \n \n \n \n\n\n \n Debureaux, P.; Cassinat, B.; Soret-Dulphy, J.; Mora, B.; Verger, E.; Maslah, N.; Plessier, A.; Rautou, P.; Ollivier-Hourman, I.; De Ledinghen, V.; Goria, O.; Bureau, C.; Siracusa, C.; Valla, D.; Giraudier, S.; Passamonti, F.; and Kiladjian, J.\n\n\n \n\n\n\n Blood Advances, 4(15): 3708–3715. August 2020.\n Publisher: American Society of Hematology\n\n\n\n
\n\n\n\n \n \n $\"Molecular$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{debureaux_molecular_2020,\n\ttitle = {Molecular profiling and risk classification of patients with myeloproliferative neoplasms and splanchnic vein thromboses},\n\tvolume = {4},\n\tissn = {2473-9529},\n\turl = {https://ashpublications.org/bloodadvances/article/4/15/3708/461754/Molecular-profiling-and-risk-classification-of},\n\tdoi = {10.1182/bloodadvances.2020002414},\n\tabstract = {Key Points. Molecular profiling of MPN-SVT may identify high-risk patients as candidates for disease-modifying therapy.JAK2V617F allele burden ≥50\\% or presence},\n\tlanguage = {en},\n\tnumber = {15},\n\turldate = {2020-08-17},\n\tjournal = {Blood Advances},\n\tauthor = {Debureaux, Pierre-Edouard and Cassinat, Bruno and Soret-Dulphy, Juliette and Mora, Barbara and Verger, Emmanuelle and Maslah, Nabih and Plessier, Aurelie and Rautou, Pierre-Emmanuel and Ollivier-Hourman, Isabelle and De Ledinghen, Victor and Goria, Odile and Bureau, Christophe and Siracusa, Claudia and Valla, Dominique and Giraudier, Stephane and Passamonti, Francesco and Kiladjian, Jean-Jacques},\n\tmonth = aug,\n\tyear = {2020},\n\tnote = {Publisher: American Society of Hematology},\n\tpages = {3708--3715},\n}\n\n

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\n \n\n \n \n \n \n \n \n Butler enables rapid cloud-based analysis of thousands of human genomes.\n \n \n \n \n\n\n \n Yakneen, S.; Waszak, S. M.; Gertz, M.; and Korbel, J. O.\n\n\n \n\n\n\n Nature Biotechnology, 38(3): 288–292. February 2020.\n Number: 3 Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"Butler$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{yakneen_butler_2020,\n\ttitle = {Butler enables rapid cloud-based analysis of thousands of human genomes},\n\tvolume = {38},\n\tcopyright = {2020 The Author(s)},\n\tissn = {1546-1696},\n\turl = {https://www.nature.com/articles/s41587-019-0360-3},\n\tdoi = {10.1038/s41587-019-0360-3},\n\tabstract = {We present Butler, a computational tool that facilitates large-scale genomic analyses on public and academic clouds. Butler includes innovative anomaly detection and self-healing functions that improve the efficiency of data processing and analysis by 43\\% compared with current approaches. Butler enabled processing of a 725-terabyte cancer genome dataset from the Pan-Cancer Analysis of Whole Genomes (PCAWG) project in a time-efficient and uniform manner.},\n\tlanguage = {en},\n\tnumber = {3},\n\turldate = {2020-08-17},\n\tjournal = {Nature Biotechnology},\n\tauthor = {Yakneen, Sergei and Waszak, Sebastian M. and Gertz, Michael and Korbel, Jan O.},\n\tmonth = feb,\n\tyear = {2020},\n\tnote = {Number: 3\nPublisher: Nature Publishing Group},\n\tpages = {288--292},\n}\n\n

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\n \n\n \n \n \n \n \n \n High prevalence of clonal hematopoiesis in the blood and bone marrow of healthy volunteers.\n \n \n \n \n\n\n \n Guermouche, H.; Ravalet, N.; Gallay, N.; Deswarte, C.; Foucault, A.; Beaud, J.; Rault, E.; Saindoy, E.; Lachot, S.; Martignoles, J.; Gissot, V.; Suner, L.; Gyan, E.; Delhommeau, F.; Herault, O.; and Hirsch, P.\n\n\n \n\n\n\n Blood Advances, 4(15): 3550–3557. August 2020.\n Publisher: American Society of Hematology\n\n\n\n
\n\n\n\n \n \n $\"High$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{guermouche_high_2020,\n\ttitle = {High prevalence of clonal hematopoiesis in the blood and bone marrow of healthy volunteers},\n\tvolume = {4},\n\tissn = {2473-9529},\n\turl = {https://ashpublications.org/bloodadvances/article/4/15/3550/461695/High-prevalence-of-clonal-hematopoiesis-in-the},\n\tdoi = {10.1182/bloodadvances.2020001582},\n\tabstract = {Key Points. CH is frequent in the bone marrow and the blood of carefully selected healthy volunteers.The detection of CH in the bone marrow must be interpreted},\n\tlanguage = {en},\n\tnumber = {15},\n\turldate = {2020-08-17},\n\tjournal = {Blood Advances},\n\tauthor = {Guermouche, Hélène and Ravalet, Noémie and Gallay, Nathalie and Deswarte, Caroline and Foucault, Amelie and Beaud, Jenny and Rault, Emmanuelle and Saindoy, Emeline and Lachot, Sébastien and Martignoles, Jean-Alain and Gissot, Valérie and Suner, Ludovic and Gyan, Emmanuel and Delhommeau, François and Herault, Olivier and Hirsch, Pierre},\n\tmonth = aug,\n\tyear = {2020},\n\tnote = {Publisher: American Society of Hematology},\n\tpages = {3550--3557},\n}\n\n

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\n \n\n \n \n \n \n \n \n Large-scale comparative evaluation of user-friendly tools for predicting variant-induced alterations of splicing regulatory elements.\n \n \n \n \n\n\n \n Tubeuf, H.; Charbonnier, C.; Soukarieh, O.; Blavier, A.; Lefebvre, A.; Dauchel, H.; Frebourg, T.; Gaildrat, P.; and Martins, A.\n\n\n \n\n\n\n Human Mutation, n/a(n/a). August 2020.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/humu.24091\n\n\n\n
\n\n\n\n \n \n $\"Large-scale$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{tubeuf_large-scale_2020,\n\ttitle = {Large-scale comparative evaluation of user-friendly tools for predicting variant-induced alterations of splicing regulatory elements},\n\tvolume = {n/a},\n\tcopyright = {© 2020 Wiley Periodicals LLC},\n\tissn = {1098-1004},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/humu.24091},\n\tdoi = {10.1002/humu.24091},\n\tabstract = {Discriminating which nucleotide variants cause disease or contribute to phenotypic traits remains a major challenge in human genetics. In theory, any intragenic variant can potentially affect RNA splicing by altering splicing regulatory elements (SREs). However, these alterations are often ignored mainly because pioneer SRE predictors have proved inefficient. Here, we report the first large-scale comparative evaluation of four user-friendly SRE-dedicated algorithms (QUEPASA, HEXplorer, SPANR, and HAL) tested both as standalone tools and in multiple combined ways based on two independent benchmark datasets adding up to {\\textgreater}1,300 exonic variants studied at the messenger RNA level and mapping to 89 different disease-causing genes. These methods display good predictive power, based on decision thresholds derived from the receiver operating characteristics curve analyses, with QUEPASA and HAL having the best accuracies either as standalone or in combination. Still, overall there was a tight race between the four predictors, suggesting that all methods may be of use. Additionally, QUEPASA and HEXplorer may be beneficial as well for predicting variant-induced creation of pseudoexons deep within introns. Our study highlights the potential of SRE predictors as filtering tools for identifying disease-causing candidates among the plethora of variants detected by high-throughput DNA sequencing and provides guidance for their use in genomic medicine settings.},\n\tlanguage = {en},\n\tnumber = {n/a},\n\turldate = {2020-08-17},\n\tjournal = {Human Mutation},\n\tauthor = {Tubeuf, Hélène and Charbonnier, Camille and Soukarieh, Omar and Blavier, André and Lefebvre, Arnaud and Dauchel, Hélène and Frebourg, Thierry and Gaildrat, Pascaline and Martins, Alexandra},\n\tmonth = aug,\n\tyear = {2020},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/humu.24091},\n\tkeywords = {BRCA1 and MAPT, MSH2, RNA splicing, exome sequencing, functional assays, in silico predictions, increased exon skipping or inclusion, molecular diagnostics, pseudoexons, splicing regulatory elements, variant interpretation},\n}\n\n

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\n \n\n \n \n \n \n \n \n Clinical features and blood iron metabolism markers in children with beta-propeller protein associated neurodegeneration.\n \n \n \n \n\n\n \n Belohlavkova, A.; Sterbova, K.; Betzler, C.; Burkhard, S.; Panzer, A.; Wolff, M.; Lassuthova, P.; Vlckova, M.; Kyncl, M.; Benova, B.; Jahodova, A.; Kudr, M.; Goerg, M.; Dusek, P.; Seeman, P.; Kluger, G.; and Krsek, P.\n\n\n \n\n\n\n European Journal of Paediatric Neurology. August 2020.\n \n\n\n\n
\n\n\n\n \n \n $\"Clinical$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{belohlavkova_clinical_2020,\n\ttitle = {Clinical features and blood iron metabolism markers in children with beta-propeller protein associated neurodegeneration},\n\tissn = {1090-3798},\n\turl = {http://www.sciencedirect.com/science/article/pii/S1090379820301549},\n\tdoi = {10.1016/j.ejpn.2020.07.010},\n\tabstract = {Background\nNeurodegeneration with brain iron accumulation constitutes a group of rare progressive movement disorders sharing intellectual disability and neuroimaging findings as common denominators. Beta-propeller protein-associated neurodegeneration (BPAN) represents approximately 7\\% of the cases, and its first signs are typically epilepsy and developmental delay. We aimed to describe in detail the phenotype of BPAN with a special focus on iron metabolism.\nMaterial and methods\nWe present a cohort of paediatric patients with pathogenic variants of WD-Repeat Domain 45 gene (WDR45). The diagnosis was established by targeted panel sequencing of genes associated with epileptic encephalopathies (n = 9) or by Sanger sequencing of WDR45 (n = 1). Data on clinical characteristics, molecular-genetic findings and other performed investigations were gathered from all participating centres. Markers of iron metabolism were analysed in 6 patients.\nResults\nTen children (3 males, 7 females, median age 8.4 years) from five centres (Prague, Berlin, Vogtareuth, Tubingen and Cologne) were enrolled in the study. All patients manifested first symptoms (e.g. epilepsy, developmental delay) between 2 and 31 months (median 16 months). Seven patients were seizure-free (6 on antiepileptic medication, one drug-free) at the time of data collection. Neurological findings were non-specific with deep tendon hyperreflexia (n = 4) and orofacial dystonia (n = 3) being the most common. Soluble transferrin receptor/log ferritin ratio was elevated in 5/6 examined subjects; other parameters of iron metabolism were normal.\nConclusion\nSeverity of epilepsy often gradually decreases in BPAN patients. Elevation of soluble transferrin receptor/log ferritin ratio could be another biochemical marker of the disease and should be explored by further studies.},\n\tlanguage = {en},\n\turldate = {2020-08-17},\n\tjournal = {European Journal of Paediatric Neurology},\n\tauthor = {Belohlavkova, Anezka and Sterbova, Katalin and Betzler, Cornelia and Burkhard, Stuve and Panzer, Axel and Wolff, Markus and Lassuthova, Petra and Vlckova, Marketa and Kyncl, Martin and Benova, Barbora and Jahodova, Alena and Kudr, Martin and Goerg, Maria and Dusek, Petr and Seeman, Pavel and Kluger, Gerhard and Krsek, Pavel},\n\tmonth = aug,\n\tyear = {2020},\n\tkeywords = {Beta-propeller protein-associated neurodegeneration, Neurodegeneration with brain iron accumulation  BPAN, Targeted gene panel sequencing},\n}\n\n

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\n \n\n \n \n \n \n \n \n Scaling up dissection of functional RNA elements.\n \n \n \n \n\n\n \n Bühler, M.; and Tuck, A. C.\n\n\n \n\n\n\n Nature Structural & Molecular Biology,1–3. August 2020.\n Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"Scaling$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{buhler_scaling_2020,\n\ttitle = {Scaling up dissection of functional {RNA} elements},\n\tcopyright = {2020 Springer Nature America, Inc.},\n\tissn = {1545-9985},\n\turl = {https://www.nature.com/articles/s41594-020-0482-9},\n\tdoi = {10.1038/s41594-020-0482-9},\n\tabstract = {Translation and mRNA decay are tightly connected processes governing protein production, and their regulation involves an elaborate network of protein factors and sequence elements. A massively parallel RNA-based reporter system now reveals regulatory pathways triggered by 5′ UTR elements and allows dissection of the interplay between translation and mRNA decay.},\n\tlanguage = {en},\n\turldate = {2020-08-17},\n\tjournal = {Nature Structural \\& Molecular Biology},\n\tauthor = {Bühler, Marc and Tuck, Alex Charles},\n\tmonth = aug,\n\tyear = {2020},\n\tnote = {Publisher: Nature Publishing Group},\n\tpages = {1--3},\n}\n\n

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\n \n\n \n \n \n \n \n \n Multisystemic manifestations in a cohort of 75 classical Ehlers-Danlos syndrome patients: natural history and nosological perspectives.\n \n \n \n \n\n\n \n Ritelli, M.; Venturini, M.; Cinquina, V.; Chiarelli, N.; and Colombi, M.\n\n\n \n\n\n\n Orphanet Journal of Rare Diseases, 15(1): 197. July 2020.\n \n\n\n\n
\n\n\n\n \n \n $\"Multisystemic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{ritelli_multisystemic_2020,\n\ttitle = {Multisystemic manifestations in a cohort of 75 classical {Ehlers}-{Danlos} syndrome patients: natural history and nosological perspectives},\n\tvolume = {15},\n\tissn = {1750-1172},\n\tshorttitle = {Multisystemic manifestations in a cohort of 75 classical {Ehlers}-{Danlos} syndrome patients},\n\turl = {https://doi.org/10.1186/s13023-020-01470-0},\n\tdoi = {10.1186/s13023-020-01470-0},\n\tabstract = {The Ehlers-Danlos syndromes (EDS) are rare connective tissue disorders consisting of 13 subtypes with overlapping features including joint hypermobility, skin and generalized connective tissue fragility. Classical EDS (cEDS) is principally caused by heterozygous COL5A1 or COL5A2 variants and rarely by the COL1A1 p.(Arg312Cys) substitution. Current major criteria are (1) skin hyperextensibility plus atrophic scars and (2) generalized joint hypermobility (gJHM). Minor criteria include additional mucocutaneous signs, epicanthal folds, gJHM complications, and an affected first-degree relative. Minimal criteria prompting molecular testing are major criterion 1 plus either major criterion 2 or 3 minor criteria. In addition to these features, the clinical picture also involves multiple organ systems, but large-scale cohort studies are still missing. This study aimed to investigate the multisystemic involvement and natural history of cEDS through a cross-sectional study on a cohort of 75 molecularly confirmed patients evaluated from 2010 to 2019 in a tertiary referral center. The diagnostic criteria, additional mucocutaneous, osteoarticular, musculoskeletal, cardiovascular, gastrointestinal, uro-gynecological, neuropsychiatric, and atopic issues, and facial/ocular features were ascertained, and feature rates compared by sex and age.},\n\tnumber = {1},\n\turldate = {2020-08-17},\n\tjournal = {Orphanet Journal of Rare Diseases},\n\tauthor = {Ritelli, Marco and Venturini, Marina and Cinquina, Valeria and Chiarelli, Nicola and Colombi, Marina},\n\tmonth = jul,\n\tyear = {2020},\n\tpages = {197},\n}\n\n

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\n \n\n \n \n \n \n \n \n Germline pathogenic variant spectrum in 25 cancer susceptibility genes in Turkish breast and colorectal cancer patients and elderly controls.\n \n \n \n \n\n\n \n Akcay, I. M.; Celik, E.; Agaoglu, N. B.; Alkurt, G.; Akgun, T. K.; Yildiz, J.; Enc, F.; Kir, G.; Canbek, S.; Kilic, A.; Zemheri, E.; Ezberci, F.; Özcelik, M.; Doganay, G. D.; and Doganay, L.\n\n\n \n\n\n\n International Journal of Cancer, n/a(n/a). July 2020.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.33199\n\n\n\n
\n\n\n\n \n \n $\"Germline$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{akcay_germline_2020,\n\ttitle = {Germline pathogenic variant spectrum in 25 cancer susceptibility genes in {Turkish} breast and colorectal cancer patients and elderly controls},\n\tvolume = {n/a},\n\tcopyright = {This article is protected by copyright. All rights reserved.},\n\tissn = {1097-0215},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.33199},\n\tdoi = {10.1002/ijc.33199},\n\tabstract = {Inherited pathogenic variants account for 5-10\\% of all breast cancer (BC) and colorectal cancer (CRC) cases. Here we sought to profile the pathogenic variants in 25 cancer susceptibility genes in Turkish population. Germline pathogenic variants were screened in 732 BC patients, 189 CRC patients, and 490 cancer-free elderly controls, using NGS-based multigene panel testing and MLPA testing. Pathogenic variants were detected in 17.2\\% of high-risk BC patients and 26.4\\% of high-risk CRC patients. More than 95\\% of these variants were clinically actionable. BRCA1/2 and mismatch repair genes (MLH1, MSH2 and MSH6) accounted for 2/3 of all pathogenic variants detected in high-risk BC and CRC patients, respectively. Pathogenic variants in PALB2, CHEK2, ATM and TP53 were also prevalent in high-risk BC patients (4.5\\%). BRCA1 exons 17-18 deletion and CHEK2 c.592+3A{\\textgreater}T were the most common variants predisposing to BC, and they are likely to be founder variants. 3 frequent MUTYH pathogenic variants (c.884C{\\textgreater}T, c.1437\\_1439delGGA, and c.1187G{\\textgreater}A) were responsible for all MUTYH biallelic cases (4.4\\% of high-risk CRC patients). The total pathogenic variant frequency was very low in controls (2.4\\%) and in low-risk BC (3.9\\%) and CRC (6.1\\%) patients. This study depicts the pathogenic variant spectrum and prevalence in Turkish BC and CRC patients, guiding clinicians and health authorities for genetic testing applications and variant classification in Turkish population. This article is protected by copyright. All rights reserved.},\n\tlanguage = {en},\n\tnumber = {n/a},\n\turldate = {2020-07-28},\n\tjournal = {International Journal of Cancer},\n\tauthor = {Akcay, Izzet Mehmet and Celik, Elifnaz and Agaoglu, Nihat Bugra and Alkurt, Gizem and Akgun, Tugba Kizilboga and Yildiz, Jale and Enc, Feruze and Kir, Gozde and Canbek, Sezin and Kilic, Ali and Zemheri, Ebru and Ezberci, Fikret and Özcelik, Melike and Doganay, Gizem Dinler and Doganay, Levent},\n\tmonth = jul,\n\tyear = {2020},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.33199},\n\tkeywords = {HCS, Hereditary Disorders, SOPHiA DDM, breast cancer, colorectal cancers, hereditary cancer predisposition, multigene panel testing},\n}\n\n

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\n \n\n \n \n \n \n \n \n Clinical Validation of a Whole Exome Sequencing Pipeline.\n \n \n \n \n\n\n \n Prosser, D. O.; Raja, I.; Kolkiewicz, K.; Milano, A.; and Love, D. R.\n\n\n \n\n\n\n Molecular Medicine. July 2020.\n Publisher: IntechOpen\n\n\n\n
\n\n\n\n \n \n $\"Clinical$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{prosser_clinical_2020,\n\ttitle = {Clinical {Validation} of a {Whole} {Exome} {Sequencing} {Pipeline}},\n\turl = {https://www.intechopen.com/online-first/clinical-validation-of-a-whole-exome-sequencing-pipeline},\n\tdoi = {10.5772/intechopen.93251},\n\tabstract = {Establishing whole exome sequencing (WES) in an accredited clinical diagnostic space is challenging. The validation (as opposed to verification) of an approach that will lead to clinical reports requires adhering to international guidelines and recommendations and developing a robust analytical pipeline that can scale due to the increasing clinical demand for comprehensive gene screening. This chapter will present a step-wise approach to WES validation that any laboratory can follow. The focus will be on highlighting the pivotal technical issues that must be addressed in validating WES and the analytical tools and QC metrics that must be considered before implementing WES in a clinical environment.},\n\tlanguage = {en},\n\turldate = {2020-07-28},\n\tjournal = {Molecular Medicine},\n\tauthor = {Prosser, Debra O. and Raja, Indu and Kolkiewicz, Kelly and Milano, Antonio and Love, Donald Roy},\n\tmonth = jul,\n\tyear = {2020},\n\tnote = {Publisher: IntechOpen},\n\tkeywords = {CNV, Exome, Genomics, Hereditary Disorders, SOPHiA DDM, WES},\n}\n\n

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\n \n\n \n \n \n \n \n \n Genomic analysis of a familial myelodysplasia/acute myeloid leukemia and inherited RUNX1 mutations without a pre-existing platelet disorder.\n \n \n \n \n\n\n \n Prieto-Conde, M. I.; Labrador, J.; Hermida, G.; Alonso, S.; Jiménez, C.; García-Álvarez, M.; Medina, A.; Balanzategui, A.; Alcoceba, M.; Sarasquete, M. E.; Puig, N.; González, V.; Gutiérrez, N. C.; García-Sanz, R.; González-Díaz, M.; and Chillón, M. d. C.\n\n\n \n\n\n\n Leukemia & Lymphoma, 61(1): 181–184. January 2020.\n \n\n\n\n
\n\n\n\n \n \n $\"Genomic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{prieto-conde_genomic_2020,\n\ttitle = {Genomic analysis of a familial myelodysplasia/acute myeloid leukemia and inherited {RUNX1} mutations without a pre-existing platelet disorder},\n\tvolume = {61},\n\tissn = {1042-8194},\n\turl = {https://doi.org/10.1080/10428194.2019.1648801},\n\tdoi = {10.1080/10428194.2019.1648801},\n\tnumber = {1},\n\turldate = {2020-02-11},\n\tjournal = {Leukemia \\& Lymphoma},\n\tauthor = {Prieto-Conde, María Isabel and Labrador, Jorge and Hermida, Gerardo and Alonso, Sara and Jiménez, Cristina and García-Álvarez, María and Medina, Alejandro and Balanzategui, Ana and Alcoceba, Miguel and Sarasquete, María Eugenia and Puig, Noemí and González, Verónica and Gutiérrez, Norma C. and García-Sanz, Ramón and González-Díaz, Marcos and Chillón, María del Carmen},\n\tmonth = jan,\n\tyear = {2020},\n\tpmid = {31385734},\n\tkeywords = {Blood, Case Study, Custom, Genomics, Hereditary Disorders, Illumina Sequencer, Myelodysplasia, Myeloid, Oncology, PanMyeloid, RUNX1, SOPHiA DDM},\n\tpages = {181--184},\n}\n\n

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\n \n\n \n \n \n \n \n \n Evaluation of KRAS, NRAS and BRAF mutations detection in plasma using an automated system for patients with metastatic colorectal cancer.\n \n \n \n \n\n\n \n Franczak, C.; Witz, A.; Geoffroy, K.; Demange, J.; Rouyer, M.; Husson, M.; Massard, V.; Gavoille, C.; Lambert, A.; and Gilson, P.\n\n\n \n\n\n\n PloS one, 15(1): e0227294. January 2020.\n \n\n\n\n
\n\n\n\n \n \n $\"Evaluation$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{franczak_evaluation_2020,\n\ttitle = {Evaluation of {KRAS}, {NRAS} and {BRAF} mutations detection in plasma using an automated system for patients with metastatic colorectal cancer},\n\tvolume = {15},\n\turl = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227294},\n\tdoi = {10.1371/journal.pone.0227294},\n\tlanguage = {English},\n\tnumber = {1},\n\tjournal = {PloS one},\n\tauthor = {Franczak, Claire and Witz, Andréa and Geoffroy, Karen and Demange, Jessica and Rouyer, Marie and Husson, Marie and Massard, Vincent and Gavoille, Céline and Lambert, Aurélien and Gilson, Pauline},\n\tmonth = jan,\n\tyear = {2020},\n\tkeywords = {BRAF, Genomics, KRAS, Liquid Biopsy, NRAS, SOPHiA DDM, STS},\n\tpages = {e0227294},\n}\n\n

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\n \n\n \n \n \n \n \n Possible implication of undescribed SMN1-SMN2 genotype in chronic EMG-pattern of SMA with transitory acute denervation.\n \n \n \n\n\n \n Vitello, G.; Calì, F.; Vinci, M.; Scuderi, C.; L'Episcopo, F.; Musumeci, A.; Musumeci, S.; and Nicotera, A.\n\n\n \n\n\n\n Journal of musculoskeletal & neuronal interactions. April 2020.\n \n\n\n\n
\n\n\n\n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{vitello_possible_2020,\n\ttitle = {Possible implication of undescribed {SMN1}-{SMN2} genotype in chronic {EMG}-pattern of {SMA} with transitory acute denervation},\n\tabstract = {Spinal muscular atrophy (SMA) refers to a group of genetic neuromuscular disorders affecting lower motor neurons causative of numerous phenotypes. To date, according to the age of onset, maximum muscular activity achieved, and life expectation four types of SMA are recognized, all caused by mutations in the SMN1 gene with SMN2 copy number influencing disease severity. Herein, we describe the case of a 31-year-old young male with normal psychomotor development who has experienced fatigue, cramps, and muscle asciculations in the lower limbs for a period of 2 months.\nBased on electrophysiological and clinical findings we performed SMA genetic, clinical exome and RNA expression of candidate genes which led us to suggest SMN1-SMN2 genes [(2+0) and (0+0)] combination as possibly being implicated in the phenotype.},\n\tjournal = {Journal of musculoskeletal \\& neuronal interactions},\n\tauthor = {Vitello, Girolamo and Calì, Francesco and Vinci, Mirella and Scuderi, Carmela and L'Episcopo, Francesca and Musumeci, Antonino and Musumeci, Sebastiano and Nicotera, Antonio},\n\tmonth = apr,\n\tyear = {2020},\n\tkeywords = {CES},\n}\n\n

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\n \n\n \n \n \n \n \n Pitfalls in CALR exon 9 mutation detection: A single-center experience in 571 positive patients.\n \n \n \n\n\n \n Verger, E.; Maslah, N.; Schlageter, M.; Chomienne, C.; Kiladjian, J.; Giraudier, S.; and Cassinat, B.\n\n\n \n\n\n\n International Journal of Laboratory Hematology. July 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{verger_pitfalls_2020,\n\ttitle = {Pitfalls in {CALR} exon 9 mutation detection: {A} single-center experience in 571 positive patients},\n\tissn = {1751-553X},\n\tshorttitle = {Pitfalls in {CALR} exon 9 mutation detection},\n\tdoi = {10.1111/ijlh.13282},\n\tabstract = {INTRODUCTION: The pathogenesis of myeloproliferative neoplasms (MPNs) is closely related to the acquisition of specific molecular alterations in JAK2, MPL, or CALR genes, the presence of which represent major diagnostic criteria in the WHO classification. The CALR exon 9 insertions and deletions are very heterogeneous, and their detection mainly relies on polymerase chain reaction (PCR) fragment length analysis.\nMETHODS: We report on the rare nonclassical profiles that we observed among the 1382 patients analyzed by PCR fragment length analysis. In difficult cases, we tested germline DNA and performed NGS analysis.\nRESULTS: We faced some troubling results because of the presence of several unexpected peaks. Our investigations showed that they resulted from a mix of isolated or double somatic mutations combined with germline alterations which could be misleading for a correct diagnosis. The precise interpretation of such difficult cases is mandatory as a misinterpretation could lead to the prescription of cytoreductive drugs to nondiseased persons or to an absence of treatment in true MPN patients.\nCONCLUSION: Our observations showed that every mutation should be verified by direct Sanger sequencing, and we show that sometimes it may be necessary to study germline DNA and to complement with NGS analysis to precisely interpret the molecular alterations.},\n\tlanguage = {eng},\n\tjournal = {International Journal of Laboratory Hematology},\n\tauthor = {Verger, Emmanuelle and Maslah, Nabih and Schlageter, Marie-Helene and Chomienne, Christine and Kiladjian, Jean-Jacques and Giraudier, Stephane and Cassinat, Bruno},\n\tmonth = jul,\n\tyear = {2020},\n\tpmid = {32614523},\n\tkeywords = {CALR, calreticulin, diagnosis, myeloproliferative neoplasms},\n}\n\n

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\n \n\n \n \n \n \n \n Activating somatic and germline TERT promoter variants in myeloid malignancies.\n \n \n \n\n\n \n Nofrini, V.; Matteucci, C.; Pellanera, F.; Gorello, P.; Di Giacomo, D.; Lema Fernandez, A. G.; Nardelli, C.; Iannotti, T.; Brandimarte, L.; Arniani, S.; Moretti, M.; Gili, A.; Roti, G.; Di Battista, V.; Colla, S.; and Mecucci, C.\n\n\n \n\n\n\n Leukemia. May 2020.\n \n\n\n\n
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@article{nofrini_activating_2020,\n\ttitle = {Activating somatic and germline {TERT} promoter variants in myeloid malignancies},\n\tissn = {1476-5551},\n\tdoi = {10.1038/s41375-020-0837-6},\n\tlanguage = {eng},\n\tjournal = {Leukemia},\n\tauthor = {Nofrini, Valeria and Matteucci, Caterina and Pellanera, Fabrizia and Gorello, Paolo and Di Giacomo, Danika and Lema Fernandez, Anair Graciela and Nardelli, Carlotta and Iannotti, Tamara and Brandimarte, Lucia and Arniani, Silvia and Moretti, Martina and Gili, Alessio and Roti, Giovanni and Di Battista, Valeria and Colla, Simona and Mecucci, Cristina},\n\tmonth = may,\n\tyear = {2020},\n\tpmid = {32366939},\n\tkeywords = {MYS},\n}\n\n

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\n \n\n \n \n \n \n \n Is tumor testing efficiency for Lynch syndrome different in rectal and colon cancer?.\n \n \n \n\n\n \n Marabelli, M.; Gandini, S.; Rafaniello, P. R.; Calvello, M.; Tolva, G.; Feroce, I.; Lazzeroni, M.; Marino, E.; Dal Molin, M.; Trovato, C.; Guerrieri-Gonzaga, A.; Petz, W. L.; Barberis, M.; Bertario, L.; and Bonanni, B.\n\n\n \n\n\n\n Digestive and Liver Disease: Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. June 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{marabelli_is_2020,\n\ttitle = {Is tumor testing efficiency for {Lynch} syndrome different in rectal and colon cancer?},\n\tissn = {1878-3562},\n\tdoi = {10.1016/j.dld.2020.06.002},\n\tabstract = {BACKGROUND: Tumor testing utility in Lynch syndrome (LS) diagnosis is established.\nAIMS: Analyze the differences between tumor testing efficiency in rectal (RC) and colon cancer (CC).\nMETHODS: We performed immunohistochemistry (IHC) for MisMatch Repair (MMR) proteins (IHC-MMR) and MicroSatellite Instability analysis (MSI) on 482 unselected primary tumors: 320 CCs and 162 RCs. Samples had proficient-IHC, deficient-IHC or borderline-IHC ("patchy" expression). MSI-H borderline-IHC tumors were considered as likely MMR-deficient. Germline testing was offered to MMR-deficient patients without BRAF mutation or MLH1 promoter hypermetilation (MLH1-Hy).\nRESULTS: We identified 51/482 (10.6\\%) MMR-defective tumors. Multivariable analysis demonstrated a significant correlation between tumor testing results with histotype, lymph-node involvement and tumor location. In particular, RC showed a lower MMR-deficiency rate than CC (p{\\textless}0.0001). Interestingly, MLH1 loss was detected in 0\\% RCs and 76.1\\% CCs, with 80\\% of them showing BRAF mutation/MLH1-Hy. A germline variant was detected in 12 out of 18 patients (mutation detection rate of 66.7\\%).\nCONCLUSION: Tumor testing results showed molecular differences between CCs and RCs, in terms of MMR proteins expression, and presence of BRAF mutation/MLH1-Hy. MSH6 variants were the most frequent ones (50\\%). Although young age at diagnosis was associated with mutation detection (p = 0.045), 33.3\\% of LS patients were {\\textgreater}50 years.},\n\tlanguage = {eng},\n\tjournal = {Digestive and Liver Disease: Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver},\n\tauthor = {Marabelli, Monica and Gandini, Sara and Rafaniello, Paola Raviele and Calvello, Mariarosaria and Tolva, Gianluca and Feroce, Irene and Lazzeroni, Matteo and Marino, Elena and Dal Molin, Matteo and Trovato, Cristina and Guerrieri-Gonzaga, Aliana and Petz, Wanda Luisa and Barberis, Massimo and Bertario, Lucio and Bonanni, Bernardo},\n\tmonth = jun,\n\tyear = {2020},\n\tpmid = {32620519},\n\tkeywords = {Immunohistochemistry (IHC) for MisMatch Repair (MMR) proteins, Lynch syndrome, MicroSatellite Instability analysis (MSI), Tumor testing},\n}\n\n

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\n \n\n \n \n \n \n \n New germline mutations in non-BRCA genes among breast cancer women of Mongoloid origin.\n \n \n \n\n\n \n Gervas, P.; Molokov, A.; Schegoleva, A.; Kiselev, A.; Babyshkina, N.; Pisareva, L.; Tyukalov, Y.; Choynzonov, E.; and Cherdyntseva, N.\n\n\n \n\n\n\n Molecular Biology Reports. June 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{gervas_new_2020,\n\ttitle = {New germline mutations in non-{BRCA} genes among breast cancer women of {Mongoloid} origin},\n\tissn = {1573-4978},\n\tdoi = {10.1007/s11033-020-05612-2},\n\tabstract = {In accordance with the Asian BRCA Consortium data, there is a significant difference in incidence rate of breast cancer depending on age, as well as spectrum and prevalence of BRCA1/2 mutations between Mongoloid (East Asian) and Caucasoid (European) people. However, European strategies to identify familial BC are still applied to the Asian population, including Russian Mongoloids (Khakas, Buryats, Tyvans and Yakuts and others). The main purpose of the study was to identify molecular changes associated with hereditary BC in Russian Mongoloid BC patients (Buryats). Thirty-nine patients were included in the study. Genomic DNA extracted from lymphocytes was used to prepare DNA-libraries. Target sequencing was designed to cover 27 genes, such as ATM, APC, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2 and others. Paired-end sequencing (2 × 150 bp) was conducted on a NextSeq 500 system (Illumina, USA). Three pathogenic mutations in non-BRCA genes were found (prevalence of 8\\%). The pathogenic mutations were found in the RAD51D and PTEN genes. The pathogenic variant in the RAD51D gene (rs137886232, NC\\_000017.10:g.33428366G{\\textgreater}A, p.R141X) was observed in two unrelated individuals aged under 40. One of these patients had a family history of late-onset stomach cancer in second-degree relatives. The pathogenic mutation in the PTEN gene (rs786201044, NC\\_000010.10:g.89692922T{\\textgreater}C, p.C136R) was observed in a 38 years old breast cancer patient with no family history. In our study, we first describe pathogenic mutations in RAD51D and PTEN genes found in young Buryat patients.},\n\tlanguage = {eng},\n\tjournal = {Molecular Biology Reports},\n\tauthor = {Gervas, Polina and Molokov, Aleksey and Schegoleva, Anastasia and Kiselev, Artem and Babyshkina, Nataliya and Pisareva, Lubov and Tyukalov, Yury and Choynzonov, Evgeny and Cherdyntseva, Nadezda},\n\tmonth = jun,\n\tyear = {2020},\n\tpmid = {32601921},\n\tkeywords = {Breast cancer, Germline mutation, Mongoloid race},\n}\n\n

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\n \n\n \n \n \n \n \n Coexistence of Three Different Mutations in a Male Infant: neurofibromatosis Type 1, Progressive Familial Intrahepatic Cholestasis Type 2 and LPIN3.\n \n \n \n\n\n \n Altay, D.; Gorukmez, O.; and Arslan, D.\n\n\n \n\n\n\n Fetal and Pediatric Pathology,1–6. June 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{altay_coexistence_2020,\n\ttitle = {Coexistence of {Three} {Different} {Mutations} in a {Male} {Infant}: neurofibromatosis {Type} 1, {Progressive} {Familial} {Intrahepatic} {Cholestasis} {Type} 2 and {LPIN3}},\n\tissn = {1551-3823},\n\tshorttitle = {Coexistence of {Three} {Different} {Mutations} in a {Male} {Infant}},\n\tdoi = {10.1080/15513815.2020.1783405},\n\tabstract = {INTRODUCTION: The coexistence of progressive familial intrahepatic cholestasis type 2, failure to thrive due to an LPIN3 mutation, and stigmata of neonatal neurofibromatosis represents a complex diagnostic challenge.\nCASE REPORT: We present a child with cholestasis requiring hepatic transplantation, explained by the progressive familial intrahepatic cholestasis type 2, failure to thrive could be contributed to by the LPIN3 mutation, and skin findings along with the family history of the patient was due to neurofibromatosis type 1.\nCONCLUSION: Our case illustrates the complexities of multiple genetic mutations in a child.},\n\tlanguage = {eng},\n\tjournal = {Fetal and Pediatric Pathology},\n\tauthor = {Altay, Derya and Gorukmez, Orhan and Arslan, Duran},\n\tmonth = jun,\n\tyear = {2020},\n\tpmid = {32597698},\n\tkeywords = {LPIN3, Neurofibromatosis, progressive familial intrahepatic cholestasis},\n\tpages = {1--6},\n}\n\n

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\n \n\n \n \n \n \n \n Characterization and in silico analyses of the BRCA1/2 variants identified in individuals with personal and/or family history of BRCA-related cancers.\n \n \n \n\n\n \n Pirim, D.; Kaya, N.; Yıldırım, E. U.; Sag, Ş. O.; and Temel, S. G.\n\n\n \n\n\n\n International Journal of Biological Macromolecules. June 2020.\n \n\n\n\n
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@article{pirim_characterization_2020,\n\ttitle = {Characterization and in silico analyses of the {BRCA1}/2 variants identified in individuals with personal and/or family history of {BRCA}-related cancers},\n\tissn = {1879-0003},\n\tdoi = {10.1016/j.ijbiomac.2020.06.222},\n\tabstract = {Pathogenic variants in the coding regions of the BRCA1/2 lead dysfunctional or nonfunctional BRCA proteins however the contribution of non-coding BRCA1/2 variants to BRCA-related disease risk has not been fully elucidated. Thus, we characterized the functional impact of both coding and non-coding BRCA1/2 variants identified in individuals with personal and/or family history of BRCA-related cancers. The data were produced by resequencing the exons and exon-intron junctions of the BRCA1/2 in 125 individuals and were comprehensively analyzed by using bioinformatics tools and databases. A total of 96 variants (59 coding and 37 non-coding) including 7 novel variants were identified and analyzed for their functional importance. We identified 11 missense variants that potentially affect protein function; 22 variants were likely to alter different types of posttranslational modifications. Also, multiple non-coding BRCA1/2 variants were found to reside in the critical regulatory regions that have the potential to act as eQTLs and affect alternative splicing. The results of our study shed light on the possible contributions of not only coding variants but also non-coding BRCA1/2 variants in BRCRA-related cancers. Further investigation is required to fully understand their potential associations with phenotypes which may ultimately lead their utilization on cancer management as a biomarker.},\n\tlanguage = {eng},\n\tjournal = {International Journal of Biological Macromolecules},\n\tauthor = {Pirim, Dilek and Kaya, Niyazi and Yıldırım, Elif Uz and Sag, Şebnem Ozemri and Temel, Sehime Gulsun},\n\tmonth = jun,\n\tyear = {2020},\n\tpmid = {32599251},\n\tkeywords = {BRCA-related cancer, BRCA1/2, In silico analyses, Next-generation sequencing, Non-coding variants},\n}\n\n

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\n \n\n \n \n \n \n \n Neurofibromatosis Type 1 Molecular Diagnosis in Turkish Patients Türk Nörofibromatozis Tip1 Hastalarında Moleküler Tanı Sonuçları.\n \n \n \n\n\n \n Bahsi, T.; and Saat, H.\n\n\n \n\n\n\n Gazi Medical Journal, 31: 406–409. June 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{bahsi_neurofibromatosis_2020,\n\ttitle = {Neurofibromatosis {Type} 1 {Molecular} {Diagnosis} in {Turkish} {Patients} {Türk} {Nörofibromatozis} {Tip1} {Hastalarında} {Moleküler} {Tanı} {Sonuçları}},\n\tvolume = {31},\n\tdoi = {10.12996/gmj.2020.97},\n\tabstract = {Neurofibromatosis type 1 (NF1) is a rare autosomal dominant, hereditary tumor-predisposition disorder. NF1 is characterized by multiple cafe-au-lait spots, multiple cutaneous neurofibromas, freckling in the axilla and inguinal area and iris Lish nodules. The prevalence is approximately 1 in 3000 individuals worldwide. In the present study, we aimed to detect the NF1 gene alterations in Turkish NF1 patients using next-generation sequencing (NGS). We analyzed 47 patients for mutations and all of them were unrelated. 27 NF1 mutations were identified. In total, 25 of the 27 mutations were likely pathogenic or pathogenic according to the ACMG criteria. Five of the pathogenic or likely pathogenic variants were novel. This is one of the large NF1 genetic studies in Turkey. We did not determine a genotype-phenotype correlation in this study because of the highly variable expressivity of the NF1 gene. According to our findings each population may have several exon regions that contain recurrent mutations. We suggest that genetic analysis with next-generation tools are more useful and helpful to provide early diagnosis and genetic counseling.},\n\tjournal = {Gazi Medical Journal},\n\tauthor = {Bahsi, Taha and Saat, Hanife},\n\tmonth = jun,\n\tyear = {2020},\n\tpages = {406--409},\n}\n\n

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\n \n\n \n \n \n \n \n \n 3-Hydroxyisobutyryl-CoA Hydrolase Deficiency in a Turkish Child with a Novel HIBCH Gene Mutation and Literature Review.\n \n \n \n \n\n\n \n Kılıç, M.; and Kurt-Çolak, F.\n\n\n \n\n\n\n Molecular Syndromology, 11(3): 170–175. July 2020.\n Publisher: Karger Publishers\n\n\n\n
\n\n\n\n \n \n $\"3-Hydroxyisobutyryl-CoA$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{kilic_3-hydroxyisobutyryl-coa_2020,\n\ttitle = {3-{Hydroxyisobutyryl}-{CoA} {Hydrolase} {Deficiency} in a {Turkish} {Child} with a {Novel} {HIBCH} {Gene} {Mutation} and {Literature} {Review}},\n\tvolume = {11},\n\tissn = {1661-8769, 1661-8777},\n\turl = {https://www.karger.com/Article/FullText/508728},\n\tdoi = {10.1159/000508728},\n\tabstract = {3-hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency (OMIM 250620) is an autosomal recessive inborn error of valine catabolism characterized by severely delayed psychomotor development, progressive neurodegeneration, recurrent metabolic attacks with intercurrent illness, increased lactic acid, cerebral atrophy, and brain lesions in the basal ganglia. \\textit{HIBCH} gene defect is a very rare organic aciduria and also might cause secondary mitochondrial dysfunction. We report a 12-month-old severely affected female infant with a novel homozygous c.556C{\\textgreater}G; p.R186G variant in the \\textit{HIBCH} gene presenting with axial hypotonia, severe developmental delay, and brain lesions in the basal ganglia and provide an overview of the literature. When suspected, newborn and selective screening with tandem mass analyses should include hydroxy-C4-carnitine to diagnose this disorder. However, in some cases, mostly in those with milder phenotype, diagnosis may be missed due to normal hydroxy-C4 carnitine levels.},\n\tlanguage = {english},\n\tnumber = {3},\n\turldate = {2020-07-07},\n\tjournal = {Molecular Syndromology},\n\tauthor = {Kılıç, Mustafa and Kurt-Çolak, Fatma},\n\tmonth = jul,\n\tyear = {2020},\n\tnote = {Publisher: Karger Publishers},\n\tpages = {170--175},\n}\n\n

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\n \n\n \n \n \n \n \n \n Abstract B058: Germline mutation spectrum in hereditary cancer syndromes in a Latin American population.\n \n \n \n \n\n\n \n Sanabria-Salas, M. C.; Guevara, G.; Rivera, A. L.; Huertas, A.; Medina, V.; Trujillo, L. M.; Peña, E.; and Wiesner, C.\n\n\n \n\n\n\n Cancer Epidemiology and Prevention Biomarkers, 29(6 Supplement 2): B058–B058. June 2020.\n Publisher: American Association for Cancer Research Section: Poster Presentations - Proffered Abstracts\n\n\n\n
\n\n\n\n \n \n $\"Abstract$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n

@article{sanabria-salas_abstract_2020,\n\ttitle = {Abstract {B058}: {Germline} mutation spectrum in hereditary cancer syndromes in a {Latin} {American} population},\n\tvolume = {29},\n\tcopyright = {©2020 American Association for Cancer Research.},\n\tissn = {1055-9965, 1538-7755},\n\tshorttitle = {Abstract {B058}},\n\turl = {https://cebp.aacrjournals.org/content/29/6_Supplement_2/B058},\n\tdoi = {10.1158/1538-7755.DISP19-B058},\n\tabstract = {Introduction: Only 4\\% of the submissions to CLINVAR are from Latin American countries, similarly to Latino/Hispanic representation in other population genetic databases. We don’t know the spectrum of mutations affecting Colombian families with hereditary cancer syndromes; moreover, these cases are under diagnosed in our Country. We aimed to identify germline risk mutations in patients with a suspected hereditary cancer syndrome who were referred for genetic counseling at the largest cancer reference Institution in Colombia (INC-E.S.E.). Materials and methods: Descriptive cohort of patients referred to genetic counseling within the Hereditary Cancer Program at the INC-E.S.E. Germline genetic studies were performed on 147 individuals through NGS multi-gene panels and confirmed with Sanger sequencing or MLPA. Genetic results from more patients will be added to these statistics as those are being analyzed. Results: So far, results were obtained from 90 patients with a foreign company to study 83 genes, and 57 additional patients were studied at the INC-E.S.E., with a panel of 105 genes from Illumina in a MiSeq. Two bioinformatic pipelines (Illumina Variant Interpreter and SOPHIA Genetics) were used. Single Nucleotide Variants (SNVs), small insertions and deletions (INDELs), and Copy Number Variants (CNVs), were classified according to the ACMG criteria. Likely pathogenic or pathogenic mutations were identified in 22\\% of the patients (32/147). Of the total number of patients with an identified hereditary breast cancer syndrome (11/147, 7.48\\%), 6 are carriers of homologous repair genes mutation (3 in BRCA1, 1 in PALB2, 1 in CHEK2 and 1 in RAD51D); in BRCA1, one corresponds to the Colombian founder mutation A1708E and two carry the mutation BRCA1: c.1674delA (p.Gly559Valfs). The second most frequent was Lynch syndrome (8/147, 5.44\\%), 4 carry mutations in MLH1, 2 in PMS2, 1 in MSH6 and 1 in MSH2. It is interesting that 3/4 patients with mutations in MLH1 had the same splicing alteration (MLH1 c.790 + 1G{\\textgreater} A). Other 5 patients with a hereditary cancer syndrome were identified, including one of each: Li-Fraumeni, Multiple Endocrine Neoplasia type 1, Von Hippel Lindau, Neurofibromatosis 1 and MUTYH - Associated Polyposis (carrier of the two most frequent mutations in MUTYH; c.1187G{\\textgreater}A \\& c.536A{\\textgreater}G). Variants of Uncertain Significance (VUSs) were found in 47.62\\% and negative results in 32.65\\%. Conclusions: The finding of pathogenic mutations in 22\\% of this cohort is similar to what was previously reported for Colombia, but the percentage of VUSs is higher than other reports. Our lack of knowledge of the mutational spectrum in Colombians and our use of extensive multigene panels can explain this VUSs high rate.\nCitation Format: María Carolina Sanabria-Salas, Gonzalo Guevara, Ana Lucía Rivera, Antonio Huertas, Vilma Medina, Lina María Trujillo, Esperanza Peña, Carolina Wiesner. Germline mutation spectrum in hereditary cancer syndromes in a Latin American population [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl\\_2):Abstract nr B058.},\n\tlanguage = {en},\n\tnumber = {6 Supplement 2},\n\turldate = {2020-07-07},\n\tjournal = {Cancer Epidemiology and Prevention Biomarkers},\n\tauthor = {Sanabria-Salas, María Carolina and Guevara, Gonzalo and Rivera, Ana Lucía and Huertas, Antonio and Medina, Vilma and Trujillo, Lina María and Peña, Esperanza and Wiesner, Carolina},\n\tmonth = jun,\n\tyear = {2020},\n\tnote = {Publisher: American Association for Cancer Research\nSection: Poster Presentations - Proffered Abstracts},\n\tkeywords = {Abstract},\n\tpages = {B058--B058},\n}\n\n

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\n Introduction: Only 4% of the submissions to CLINVAR are from Latin American countries, similarly to Latino/Hispanic representation in other population genetic databases. We don’t know the spectrum of mutations affecting Colombian families with hereditary cancer syndromes; moreover, these cases are under diagnosed in our Country. We aimed to identify germline risk mutations in patients with a suspected hereditary cancer syndrome who were referred for genetic counseling at the largest cancer reference Institution in Colombia (INC-E.S.E.). Materials and methods: Descriptive cohort of patients referred to genetic counseling within the Hereditary Cancer Program at the INC-E.S.E. Germline genetic studies were performed on 147 individuals through NGS multi-gene panels and confirmed with Sanger sequencing or MLPA. Genetic results from more patients will be added to these statistics as those are being analyzed. Results: So far, results were obtained from 90 patients with a foreign company to study 83 genes, and 57 additional patients were studied at the INC-E.S.E., with a panel of 105 genes from Illumina in a MiSeq. Two bioinformatic pipelines (Illumina Variant Interpreter and SOPHIA Genetics) were used. Single Nucleotide Variants (SNVs), small insertions and deletions (INDELs), and Copy Number Variants (CNVs), were classified according to the ACMG criteria. Likely pathogenic or pathogenic mutations were identified in 22% of the patients (32/147). Of the total number of patients with an identified hereditary breast cancer syndrome (11/147, 7.48%), 6 are carriers of homologous repair genes mutation (3 in BRCA1, 1 in PALB2, 1 in CHEK2 and 1 in RAD51D); in BRCA1, one corresponds to the Colombian founder mutation A1708E and two carry the mutation BRCA1: c.1674delA (p.Gly559Valfs). The second most frequent was Lynch syndrome (8/147, 5.44%), 4 carry mutations in MLH1, 2 in PMS2, 1 in MSH6 and 1 in MSH2. It is interesting that 3/4 patients with mutations in MLH1 had the same splicing alteration (MLH1 c.790 + 1G\\textgreater A). Other 5 patients with a hereditary cancer syndrome were identified, including one of each: Li-Fraumeni, Multiple Endocrine Neoplasia type 1, Von Hippel Lindau, Neurofibromatosis 1 and MUTYH - Associated Polyposis (carrier of the two most frequent mutations in MUTYH; c.1187G\\textgreaterA & c.536A\\textgreaterG). Variants of Uncertain Significance (VUSs) were found in 47.62% and negative results in 32.65%. Conclusions: The finding of pathogenic mutations in 22% of this cohort is similar to what was previously reported for Colombia, but the percentage of VUSs is higher than other reports. Our lack of knowledge of the mutational spectrum in Colombians and our use of extensive multigene panels can explain this VUSs high rate. Citation Format: María Carolina Sanabria-Salas, Gonzalo Guevara, Ana Lucía Rivera, Antonio Huertas, Vilma Medina, Lina María Trujillo, Esperanza Peña, Carolina Wiesner. Germline mutation spectrum in hereditary cancer syndromes in a Latin American population [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B058.\n

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\n \n\n \n \n \n \n \n Genetic panel screening in patients with clinically unclassified systemic autoinflammatory diseases.\n \n \n \n\n\n \n Demir, F.; Doğan, Ö. A.; Demirkol, Y. K.; Tekkuş, K. E.; Canbek, S.; Karadağ, Ş. G.; Sönmez, H. E.; Ayaz, N. A.; Doğanay, H. L.; and Sözeri, B.\n\n\n \n\n\n\n Clinical Rheumatology. May 2020.\n \n\n\n\n
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@article{demir_genetic_2020,\n\ttitle = {Genetic panel screening in patients with clinically unclassified systemic autoinflammatory diseases},\n\tissn = {1434-9949},\n\tdoi = {10.1007/s10067-020-05108-1},\n\tabstract = {OBJECTIVE: Systemic autoinflammatory diseases (SAIDs) may not always present with typical clinical findings of a monogenic disease. We aimed to genetically screen and diagnose these clinically unclassified patients by next-generation sequencing (NGS) analysis.\nMETHOD: A total of 64 patients who had clinical findings of a periodic fever syndrome but did not meet the clinical diagnostic criteria for any SAID or had clinical findings for more than one monogenic SAID were identified as "clinically unclassified SAIDs." NGS panel analysis, including 16 genes, was performed in these patients. Patients, who could not be classified as one of the defined SAID after the result of the NGS gene analysis, were identified as "undefined SAID."\nRESULTS: The most common autoinflammatory symptoms in unclassified SAID patients were abdominal pain (60.9\\%), arthralgia (48.4\\%), urticarial rash (43.8\\%), myalgia (40.6\\%), oral aphthae (28.1\\%), and conjunctivitis (20.3\\%), respectively. In the result of the NGS gene panel screening, pathogenic, likely pathogenic variants, or VUS (variants of uncertain significance) were detected in 36 of 64 patients in at least one gene in the NGS panel. A total of 15 patients were diagnosed with a monogenic SAID according to both phenotypic and genotypic data; 12 patients as FMF, two patients as FCAS, and one patient as TRAPS, respectively. A total of 49 patients who did not meet the classification criteria including genetic results for a monogenic SAID were followed as undefined SAID.\nCONCLUSIONS: The classification criteria described for SAIDs so far unfortunately do not cover all patients with signs of periodic fevers. The NGS gene panel appears to be a useful diagnostic tool for some of the patients with clinically unclassified SAID findings.Key Points• The classification criteria described for SAIDs do not cover all patients with signs of periodic fevers• The use of the undefined SAID nomenclature will benefit clinicians for diagnosis and initiating early treatment• The NGS panel appears to be a useful diagnostic tool in patients with clinically unclassified SAIDs.},\n\tlanguage = {eng},\n\tjournal = {Clinical Rheumatology},\n\tauthor = {Demir, Ferhat and Doğan, Özlem Akgün and Demirkol, Yasemin Kendir and Tekkuş, Kübra Ermiş and Canbek, Sezin and Karadağ, Şerife Gül and Sönmez, Hafize Emine and Ayaz, Nuray Aktay and Doğanay, Hamdi Levent and Sözeri, Betül},\n\tmonth = may,\n\tyear = {2020},\n\tpmid = {32458238},\n\tkeywords = {Next-generation sequencing, Periodic fever syndromes, Systemic autoinflammatory diseases, Unclassified, Undefined},\n}\n\n

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\n OBJECTIVE: Systemic autoinflammatory diseases (SAIDs) may not always present with typical clinical findings of a monogenic disease. We aimed to genetically screen and diagnose these clinically unclassified patients by next-generation sequencing (NGS) analysis. METHOD: A total of 64 patients who had clinical findings of a periodic fever syndrome but did not meet the clinical diagnostic criteria for any SAID or had clinical findings for more than one monogenic SAID were identified as \"clinically unclassified SAIDs.\" NGS panel analysis, including 16 genes, was performed in these patients. Patients, who could not be classified as one of the defined SAID after the result of the NGS gene analysis, were identified as \"undefined SAID.\" RESULTS: The most common autoinflammatory symptoms in unclassified SAID patients were abdominal pain (60.9%), arthralgia (48.4%), urticarial rash (43.8%), myalgia (40.6%), oral aphthae (28.1%), and conjunctivitis (20.3%), respectively. In the result of the NGS gene panel screening, pathogenic, likely pathogenic variants, or VUS (variants of uncertain significance) were detected in 36 of 64 patients in at least one gene in the NGS panel. A total of 15 patients were diagnosed with a monogenic SAID according to both phenotypic and genotypic data; 12 patients as FMF, two patients as FCAS, and one patient as TRAPS, respectively. A total of 49 patients who did not meet the classification criteria including genetic results for a monogenic SAID were followed as undefined SAID. CONCLUSIONS: The classification criteria described for SAIDs so far unfortunately do not cover all patients with signs of periodic fevers. The NGS gene panel appears to be a useful diagnostic tool for some of the patients with clinically unclassified SAID findings.Key Points• The classification criteria described for SAIDs do not cover all patients with signs of periodic fevers• The use of the undefined SAID nomenclature will benefit clinicians for diagnosis and initiating early treatment• The NGS panel appears to be a useful diagnostic tool in patients with clinically unclassified SAIDs.\n

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\n \n\n \n \n \n \n \n Expanding the phenotype spectrum associated with pathogenic variants in the COL2A1 and COL11A1 genes.\n \n \n \n\n\n \n Čopíková, J.; Paděrová, J.; Románková, V.; Havlovicová, M.; Balaščáková, M.; Zelinová, M.; Vejvalková, Š.; Simandlová, M.; Štěpánková, J.; Hořínová, V.; Kantorová, E.; Křečková, G.; Pospíšilová, J.; Boday, A.; Meszarosová, A. U.; Turnovec, M.; Votýpka, P.; Lišková, P.; and Kremlíková Pourová, R.\n\n\n \n\n\n\n Annals of Human Genetics. May 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{copikova_expanding_2020,\n\ttitle = {Expanding the phenotype spectrum associated with pathogenic variants in the {COL2A1} and {COL11A1} genes},\n\tissn = {1469-1809},\n\tdoi = {10.1111/ahg.12386},\n\tabstract = {We report the clinical findings of 26 individuals from 16 unrelated families carrying variants in the COL2A1 or COL11A1 genes. Using Sanger and next-generation sequencing, 11 different COL2A1 variants (seven novel), were identified in 13 families (19 affected individuals), all diagnosed with Stickler syndrome (STL) type 1. In nine families, the COL2A1 disease-causing variant arose de novo. Phenotypically, we observed myopia (95\\%) and retinal detachment (47\\%), joint hyperflexibility (92\\%), midface retrusion (84\\%), cleft palate (53\\%), and various degrees of hearing impairment (50\\%). One patient had a splenic artery aneurysm. One affected individual carrying pathogenic variant in COL2A1 showed no ocular signs including no evidence of membranous vitreous anomaly. In three families (seven affected individuals), three novel COL11A1 variants were found. The propositus with a de novo variant showed an ultrarare Marshall/STL overlap. In the second family, the only common clinical sign was postlingual progressive sensorineural hearing impairment (DFNA37). Affected individuals from the third family had typical STL2 signs. The spectrum of disease phenotypes associated with COL2A1 or COL11A1 variants continues to expand and includes typical STL and various bone dysplasias, but also nonsyndromic hearing impairment, isolated myopia with or without retinal detachment, and STL phenotype without clinically detectable ocular pathology.},\n\tlanguage = {eng},\n\tjournal = {Annals of Human Genetics},\n\tauthor = {Čopíková, Jana and Paděrová, Jana and Románková, Věra and Havlovicová, Markéta and Balaščáková, Miroslava and Zelinová, Michaela and Vejvalková, Šárka and Simandlová, Martina and Štěpánková, Jana and Hořínová, Věra and Kantorová, Eva and Křečková, Gabriela and Pospíšilová, Jana and Boday, Arpád and Meszarosová, Anna Uhrová and Turnovec, Marek and Votýpka, Pavel and Lišková, Petra and Kremlíková Pourová, Radka},\n\tmonth = may,\n\tyear = {2020},\n\tpmid = {32427345},\n\tkeywords = {COL11A1, COL2A1, Marshall syndrome, Stickler syndrome, myopia, nonsyndromic hearing loss, retinal detachment},\n}\n\n

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\n \n\n \n \n \n \n \n Strategy for identification of a potential inherited leukemia predisposition in a 299 patient's cohort with tumor-only sequencing data.\n \n \n \n\n\n \n Aguilera-Diaz, A.; Larrayoz, M. J.; Palomino-Echeverría, S.; Vazquez, I.; Ariceta, B.; Mañú, A.; Blasco-Iturri, Z.; Bernal Del Castillo, T.; Olivares Salaverri, M.; Olave Rubio, M. T.; Rifon-Roca, J.; Alfonso-Pierola, A.; Prosper, F.; Fernandez-Mercado, M.; and Calasanz, M. J.\n\n\n \n\n\n\n Leukemia Research, 95: 106386. May 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{aguilera-diaz_strategy_2020,\n\ttitle = {Strategy for identification of a potential inherited leukemia predisposition in a 299 patient's cohort with tumor-only sequencing data},\n\tvolume = {95},\n\tissn = {1873-5835},\n\tdoi = {10.1016/j.leukres.2020.106386},\n\tabstract = {Myeloid neoplasms (MN) are usually sporadic late-onset cancers; nevertheless, growing evidence suggests that ∼5\\% of the cases could emerge as a consequence of inherited predisposition. Distinguishing somatic from germline variants is of vital importance, in order to establish an appropriate individualized management and counsel the patients and their relatives. Since many of the genes associated with myeloid neoplasm germline predisposition (MNGP) are also affected in sporadic MN, we intended to design a strategy to identify potentially inherited variants in a tumor only NGS panel in a cohort of 299 patients with a variety of MN. We considered as indicative of potential inherited origin, variants detected in BM sample at a ∼50\\% VAF classified as pathogenic, likely pathogenic or of unknown significance detected in MNGP-related genes. A total of 104 suspicious variants from 90 patients were filtered-in in tumor samples. Mutational patterns, follow-up data, and sequencing of a range of non-myeloid tissues were used for narrowing down the list of suspicious variants, and ultimately discriminate their nature. Our data supports the importance of considering variants found upon tumor-only sequencing as potentially of germline origin, and we offer a pipeline to define the nature of the variants.},\n\tlanguage = {eng},\n\tjournal = {Leukemia Research},\n\tauthor = {Aguilera-Diaz, Almudena and Larrayoz, María José and Palomino-Echeverría, Sara and Vazquez, Iria and Ariceta, Beñat and Mañú, Amagoia and Blasco-Iturri, Zuriñe and Bernal Del Castillo, Teresa and Olivares Salaverri, Matxalen and Olave Rubio, Maria Teresa and Rifon-Roca, Jose and Alfonso-Pierola, Ana and Prosper, Felipe and Fernandez-Mercado, Marta and Calasanz, María José},\n\tmonth = may,\n\tyear = {2020},\n\tpmid = {32512379},\n\tkeywords = {Genetic counseling, Germline, Myeloid, Myeloid neoplasms predisposition, NGS},\n\tpages = {106386},\n}\n\n

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\n \n\n \n \n \n \n \n \n Influence of gradient difference loss on MR to PET brain image synthesis using GANs.\n \n \n \n \n\n\n \n Hognon, C.; Tixier, F.; Colin, T.; Gallinato, O.; Visvikis, D.; and Jaouen, V.\n\n\n \n\n\n\n Journal of Nuclear Medicine, 61(supplement 1): 1431–1431. May 2020.\n Publisher: Society of Nuclear Medicine\n\n\n\n
\n\n\n\n \n \n $\"Influence$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{hognon_influence_2020,\n\ttitle = {Influence of gradient difference loss on {MR} to {PET} brain image synthesis using {GANs}},\n\tvolume = {61},\n\tissn = {0161-5505, 2159-662X},\n\turl = {http://jnm.snmjournals.org/content/61/supplement_1/1431},\n\tabstract = {1431\nObjectives: Considerable improvements in image synthesis have been achieved over the recent years using (deep) machine learning. Models based on generative adversarial neural networks (GANs) now enable the generation of high definition images capable of fooling the human eye. These methods are being increasingly used in medical imaging for various cross-modality image synthesis applications. The performances achieved however largely depend upon the different terms of the cost function to be minimized by the neural network. In this work, we explore the potential advantage of embedding a gradient difference loss in the cost function of GANs for MR to PET brain image synthesis, with the aim of enforcing the sharpness of functional regions in synthetic PET outputs. While not clinically meaningful, such synthetic images may be useful to generate additional data required for the training of various machine learning models or to help analyzing relationships between the two modalities.\nMethods: We used the publicly available PET-SORTEO database (CERMEP, Lyon, France) consisting of 15 highly realistic simulated volumetric brain MR and PET images. We focused the current study on T1-weighted MR to FDG-PET image synthesis. Volumetric images were resliced into 256x256 axial slices to be fed to a 2D image-to-image translation GAN architecture (pix2pix). The loss function of the proposed neural network consisted of the two losses classically found in pix2pix : Adversarial Loss (AL) and Pixel Loss (PL), and of an additional Gradient Difference Loss (GDL) enforcing consistency between gradient energies in both modalities. Network weights were optimized for 100 epochs using a NVIDIA RTX 2070 GPU card. The dataset was splitted between training (10 subjects, 2560 axial slices) and testing (5 subjects, 1280 axial slices). Results using AL+PL+GDL were compared to a baseline image-to-image translation GAN using AL+PL only. Two different weightings λ of the strength of the GDL were considered (λ=10 and λ=16). Quantitative evaluation was carried out using average root mean square error (RMSE, lower means better) and structural similarity (SSIM, higher means better) between the synthesized outputs and the simulated FDG images. Slice-wise results along the transaxial direction were also studied to analyze the method’s performances across the field of view.\nResults: Images obtained with AL+PL+GDL showed superior overall quality compared to AL+PL only. Consistently superior preservation of functional regions uptake was achieved, especially in subcortical regions striatum and thalamus. These visual observations were supported quantitatively both in terms of RMSE for GDL weighting λ=10 (15.35±1.17 for AL+PL against 15.07 ± 1.16 for AL+PL+GDL) and SSIM (0.68 ± 0.18 for AL+PL against 0.77 ± 0.24 for AL+PL+GDL). Visual quality seemed to increase with higher GDL weighting λ=16, although this observation did not reflect quantitatively with the metrics studied. Conclusion: This preliminary study suggested the potential interest of encouraging the preservation of gradient energy in the brain for MR to PET translation GANs. Sharpness and finer details of functional regions were better recovered when compared to baseline. Results were obtained on realistic simulated images. Future experiments will be conducted on real clinical data using larger cohorts and more quantitative metrics to further characterize the benefits of GDL for MR to PET image translation. Acknowledgments: this work has received support from the French National Research Agency under the "Investissements d'avenir" program bearing the reference ANR-17-RHUS-0005. View larger version: In this page In a new window Download as PowerPoint Slide},\n\tlanguage = {en},\n\tnumber = {supplement 1},\n\turldate = {2020-07-07},\n\tjournal = {Journal of Nuclear Medicine},\n\tauthor = {Hognon, Clement and Tixier, Florent and Colin, Thierry and Gallinato, Olivier and Visvikis, Dimitris and Jaouen, Vincent},\n\tmonth = may,\n\tyear = {2020},\n\tnote = {Publisher: Society of Nuclear Medicine},\n\tpages = {1431--1431},\n}\n\n

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\n 1431 Objectives: Considerable improvements in image synthesis have been achieved over the recent years using (deep) machine learning. Models based on generative adversarial neural networks (GANs) now enable the generation of high definition images capable of fooling the human eye. These methods are being increasingly used in medical imaging for various cross-modality image synthesis applications. The performances achieved however largely depend upon the different terms of the cost function to be minimized by the neural network. In this work, we explore the potential advantage of embedding a gradient difference loss in the cost function of GANs for MR to PET brain image synthesis, with the aim of enforcing the sharpness of functional regions in synthetic PET outputs. While not clinically meaningful, such synthetic images may be useful to generate additional data required for the training of various machine learning models or to help analyzing relationships between the two modalities. Methods: We used the publicly available PET-SORTEO database (CERMEP, Lyon, France) consisting of 15 highly realistic simulated volumetric brain MR and PET images. We focused the current study on T1-weighted MR to FDG-PET image synthesis. Volumetric images were resliced into 256x256 axial slices to be fed to a 2D image-to-image translation GAN architecture (pix2pix). The loss function of the proposed neural network consisted of the two losses classically found in pix2pix : Adversarial Loss (AL) and Pixel Loss (PL), and of an additional Gradient Difference Loss (GDL) enforcing consistency between gradient energies in both modalities. Network weights were optimized for 100 epochs using a NVIDIA RTX 2070 GPU card. The dataset was splitted between training (10 subjects, 2560 axial slices) and testing (5 subjects, 1280 axial slices). Results using AL+PL+GDL were compared to a baseline image-to-image translation GAN using AL+PL only. Two different weightings λ of the strength of the GDL were considered (λ=10 and λ=16). Quantitative evaluation was carried out using average root mean square error (RMSE, lower means better) and structural similarity (SSIM, higher means better) between the synthesized outputs and the simulated FDG images. Slice-wise results along the transaxial direction were also studied to analyze the method’s performances across the field of view. Results: Images obtained with AL+PL+GDL showed superior overall quality compared to AL+PL only. Consistently superior preservation of functional regions uptake was achieved, especially in subcortical regions striatum and thalamus. These visual observations were supported quantitatively both in terms of RMSE for GDL weighting λ=10 (15.35±1.17 for AL+PL against 15.07 ± 1.16 for AL+PL+GDL) and SSIM (0.68 ± 0.18 for AL+PL against 0.77 ± 0.24 for AL+PL+GDL). Visual quality seemed to increase with higher GDL weighting λ=16, although this observation did not reflect quantitatively with the metrics studied. Conclusion: This preliminary study suggested the potential interest of encouraging the preservation of gradient energy in the brain for MR to PET translation GANs. Sharpness and finer details of functional regions were better recovered when compared to baseline. Results were obtained on realistic simulated images. Future experiments will be conducted on real clinical data using larger cohorts and more quantitative metrics to further characterize the benefits of GDL for MR to PET image translation. Acknowledgments: this work has received support from the French National Research Agency under the \"Investissements d'avenir\" program bearing the reference ANR-17-RHUS-0005. View larger version: In this page In a new window Download as PowerPoint Slide\n

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\n \n\n \n \n \n \n \n Dental anomalies as a possible clue of 1p36 deletion syndrome due to germline mosaicism: a case report.\n \n \n \n\n\n \n Nistico', D.; Guidolin, F.; Navarra, C. O.; Bobbo, M.; Magnolato, A.; D'Adamo, A. P.; Giorgio, E.; Pivetta, B.; Barbi, E.; Gasparini, P.; Cadenaro, M.; and Sirchia, F.\n\n\n \n\n\n\n BMC pediatrics, 20(1): 201. May 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{nistico_dental_2020,\n\ttitle = {Dental anomalies as a possible clue of 1p36 deletion syndrome due to germline mosaicism: a case report},\n\tvolume = {20},\n\tissn = {1471-2431},\n\tshorttitle = {Dental anomalies as a possible clue of 1p36 deletion syndrome due to germline mosaicism},\n\tdoi = {10.1186/s12887-020-02049-1},\n\tabstract = {BACKGROUND: Monosomy 1p36 is the most common terminal deletion syndrome with an autosomal dominant pattern of inheritance. This syndrome is defined by an extremely wide spectrum of characteristics; however, developmental delay and intellectual disability of various degree are present in all patients and about the 90\\% of patients have a severe intellectual disability. Dental agenesis or other dental anomalies have not been described in previous reports.\nCASE PRESENTATION: We report the case of two little sisters born from healthy and non-consanguineous parents, presenting with dental anomalies and one of them with epilepsy, dilated cardiomyopathy with left-ventricular non-compaction, strabismus, history of poor growth, hypotonia and mild language delay. Patients were evaluated in several departments (genetic, child neuropsychiatric, cardiology, odontostomatology, ophthalmology, otorhinolaryngology) of Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy. They underwent investigations such as electrocardiogram, echocardiogram, dental orthopantomography X-Ray and Computed Tomography, electroencephalograms, abdomen ultrasound, blood tests, IQ tests, genetic analysis. They both have an Intelligence Quotient greater than 70 and a negative neurologic exam. Each sister carries the same 1p36 deletion of about 2.3 Mb. Genetic analysis of the parents' blood samples (Single Nucleotide Polymorphism- array, karyotype and Fluorescent In Situ Hybridization) did not reveal any deletion, translocation or inversion and confirmed the paternity. A third sib of the probands does not carry the 1p36 deletion or other quantitative alterations.\nCONCLUSION: This report describes a new trait linked to monosomy 1p36, namely a mild intellectual outcome associated with significant dental anomalies. Our finding suggests that 1p36 deletion syndrome may present with a mild cognitive impairment or even with a normal intellectual development: this is very important for the genetic counselling, especially in a prenatal setting. Moreover, we report the third study with recurrent 1p36 deletion syndrome in two siblings, likely due to germline mosaicism. Finally, we believe that the dental anomalies should be investigated in 1p36 deletion syndrome and that the spectrum of the condition could be broader than we assume.},\n\tlanguage = {eng},\n\tnumber = {1},\n\tjournal = {BMC pediatrics},\n\tauthor = {Nistico', D. and Guidolin, F. and Navarra, C. O. and Bobbo, M. and Magnolato, A. and D'Adamo, A. P. and Giorgio, E. and Pivetta, B. and Barbi, E. and Gasparini, P. and Cadenaro, M. and Sirchia, F.},\n\tmonth = may,\n\tyear = {2020},\n\tpmid = {32386509},\n\tpmcid = {PMC7210666},\n\tkeywords = {1p36 deletion syndrome, Case report, Dental anomalies, Germline mosaicism, Intellectual disability, Monosomy 1p36 syndrome, Recurrent microdeletion},\n\tpages = {201},\n}\n\n

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\n BACKGROUND: Monosomy 1p36 is the most common terminal deletion syndrome with an autosomal dominant pattern of inheritance. This syndrome is defined by an extremely wide spectrum of characteristics; however, developmental delay and intellectual disability of various degree are present in all patients and about the 90% of patients have a severe intellectual disability. Dental agenesis or other dental anomalies have not been described in previous reports. CASE PRESENTATION: We report the case of two little sisters born from healthy and non-consanguineous parents, presenting with dental anomalies and one of them with epilepsy, dilated cardiomyopathy with left-ventricular non-compaction, strabismus, history of poor growth, hypotonia and mild language delay. Patients were evaluated in several departments (genetic, child neuropsychiatric, cardiology, odontostomatology, ophthalmology, otorhinolaryngology) of Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy. They underwent investigations such as electrocardiogram, echocardiogram, dental orthopantomography X-Ray and Computed Tomography, electroencephalograms, abdomen ultrasound, blood tests, IQ tests, genetic analysis. They both have an Intelligence Quotient greater than 70 and a negative neurologic exam. Each sister carries the same 1p36 deletion of about 2.3 Mb. Genetic analysis of the parents' blood samples (Single Nucleotide Polymorphism- array, karyotype and Fluorescent In Situ Hybridization) did not reveal any deletion, translocation or inversion and confirmed the paternity. A third sib of the probands does not carry the 1p36 deletion or other quantitative alterations. CONCLUSION: This report describes a new trait linked to monosomy 1p36, namely a mild intellectual outcome associated with significant dental anomalies. Our finding suggests that 1p36 deletion syndrome may present with a mild cognitive impairment or even with a normal intellectual development: this is very important for the genetic counselling, especially in a prenatal setting. Moreover, we report the third study with recurrent 1p36 deletion syndrome in two siblings, likely due to germline mosaicism. Finally, we believe that the dental anomalies should be investigated in 1p36 deletion syndrome and that the spectrum of the condition could be broader than we assume.\n

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\n \n\n \n \n \n \n \n A Circulating Bioreactor Reprograms Cancer Cells Toward a More Mesenchymal Niche.\n \n \n \n\n\n \n Calamak, S.; Ermis, M.; Sun, H.; Islam, S.; Sikora, M.; Nguyen, M.; Hasirci, V.; Steinmetz, L. M.; and Demirci, U.\n\n\n \n\n\n\n Advanced Biosystems, 4(2): e1900139. February 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{calamak_circulating_2020,\n\ttitle = {A {Circulating} {Bioreactor} {Reprograms} {Cancer} {Cells} {Toward} a {More} {Mesenchymal} {Niche}},\n\tvolume = {4},\n\tissn = {2366-7478},\n\tdoi = {10.1002/adbi.201900139},\n\tabstract = {Cancer is a complex and heterogeneous disease, and cancer cells dynamically interact with the mechanical microenvironment such as hydrostatic pressure, fluid shear, and interstitial flow. These factors play an essential role in cell fate and circulating tumor cell heterogeneity, and can influence the cellular phenotype. In this study, a peristaltic continuous flow reactor is designed and applied to HCT-116 colorectal carcinoma cells to mimic the fluid dynamics of circulation. With this intervention, a CD44/CD24-cell subpopulation emerges, and 100 genes are significantly regulated. The expression of cells at 4 h in the flow reactor is very similar to TGF-ß treatment, which is an inducer of epithelial-mesenchymal transition. ATF3 and SERPINE1 are significantly upregulated in these groups, suggesting that the mesenchymal transition is induced through this signaling pathway. This flow reactor model is satisfactory on its own to reprogram colorectal cancer cells toward a more mesenchymal niche mimicking circulation of the blood.},\n\tlanguage = {eng},\n\tnumber = {2},\n\tjournal = {Advanced Biosystems},\n\tauthor = {Calamak, Semih and Ermis, Menekse and Sun, Han and Islam, Saiful and Sikora, Michael and Nguyen, Michelle and Hasirci, Vasif and Steinmetz, Lars M. and Demirci, Utkan},\n\tmonth = feb,\n\tyear = {2020},\n\tpmid = {32293132},\n\tkeywords = {bioreactors, circulating tumor cells, epithelial to mesenchymal transition, fluidics, programming, shear force},\n\tpages = {e1900139},\n}\n\n

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\n \n\n \n \n \n \n \n Clonal hematopoiesis predicts development of therapy-related myeloid neoplasms post-autologous stem cell transplantation.\n \n \n \n\n\n \n Soerensen, J. F.; Aggerholm, A.; Kerndrup, G. B.; Hansen, M. C.; Ewald, I. K. L.; Bill, M.; Ebbesen, L. H.; Rosenberg, C. A.; Hokland, P.; Ludvigsen, M.; and Stidsholt Roug, A.\n\n\n \n\n\n\n Blood Advances, 4(5): 885–892. March 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{soerensen_clonal_2020,\n\ttitle = {Clonal hematopoiesis predicts development of therapy-related myeloid neoplasms post-autologous stem cell transplantation},\n\tvolume = {4},\n\tissn = {2473-9537},\n\tdoi = {10.1182/bloodadvances.2019001157},\n\tabstract = {Therapy-related myeloid neoplasms (tMN) develop after exposure to cytotoxic and radiation therapy, and due to their adverse prognosis, it is of paramount interest to identify patients at high risk. The presence of clonal hematopoiesis has been shown to increase the risk of developing tMN. The value of analyzing hematopoietic stem cells harvested at leukapheresis before autologous stem cell transplantation (ASCT) with next-generation sequencing and immunophenotyping represents potentially informative parameters that have yet to be discovered. We performed a nested case-control study to elucidate the association between clonal hematopoiesis, mobilization potential, and aberrant immunophenotype in leukapheresis products with the development of tMN after ASCT. A total of 36 patients with nonmyeloid disease who were diagnosed with tMN after treatment with ASCT were included as case subjects. Case subjects were identified from a cohort of 1130 patients treated with ASCT and matched with 36 control subjects who did not develop tMN after ASCT. Case subjects were significantly poorer mobilizers of CD34+ cells at leukapheresis (P = .016), indicating that these patients possess inferior bone marrow function. Both clonal hematopoiesis (odds ratio, 5.9; 95\\% confidence interval, 1.8-19.1; P = .003) and aberrant expression of CD7 (odds ratio, 6.6; 95\\% confidence interval, 1.6-26.2; P = .004) at the time of ASCT were associated with an increased risk of developing tMN after ASCT. In conclusion, clonal hematopoiesis, present at low variant allele frequencies, and aberrant CD7 expression on stem cells in leukapheresis products from patients with nonmyeloid hematologic cancer hold potential for the early identification of patients at high risk of developing tMN after ASCT.},\n\tlanguage = {eng},\n\tnumber = {5},\n\tjournal = {Blood Advances},\n\tauthor = {Soerensen, Johannes Frasez and Aggerholm, Anni and Kerndrup, Gitte Birk and Hansen, Marcus Celik and Ewald, Ina Kathrine Lykke and Bill, Marie and Ebbesen, Lene Hyldahl and Rosenberg, Carina Agerbo and Hokland, Peter and Ludvigsen, Maja and Stidsholt Roug, Anne},\n\tmonth = mar,\n\tyear = {2020},\n\tpmid = {32150606},\n\tpmcid = {PMC7065480},\n\tpages = {885--892},\n}\n\n

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\n \n\n \n \n \n \n \n \n Chapter 21 - Artificial intelligence in precision health: Systems in practice.\n \n \n \n \n\n\n \n Lugo Reyes, S. O.\n\n\n \n\n\n\n In Barh, D., editor(s), Artificial Intelligence in Precision Health, pages 499–519. Academic Press, January 2020.\n \n\n\n\n
\n\n\n\n \n \n $\"Chapter$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@incollection{lugo_reyes_chapter_2020,\n\ttitle = {Chapter 21 - {Artificial} intelligence in precision health: {Systems} in practice},\n\tisbn = {978-0-12-817133-2},\n\tshorttitle = {Chapter 21 - {Artificial} intelligence in precision health},\n\turl = {http://www.sciencedirect.com/science/article/pii/B9780128171332000215},\n\tabstract = {The field of medicine has been slow to adopt artificial intelligence (AI) techniques. Although most data in health care is unstructured, clinicians could greatly benefit from a systematic bias-free approach to pattern recognition and conditional probability to generate differential diagnoses and assist the daily task of making quick decisions under uncertainty. As of late, examples of applications and health-tech companies have proliferated. We believe the trend is clear, and the race to ground-breaking innovation is on. This chapter provides a brief history of AI efforts during the past decades, several examples of machine-learning techniques that have been applied to medical diagnosis, and a list of health-care tech companies that are leading the way in genomic discovery, image recognition, differential diagnosis generation, and the general endeavor of bringing AI to precision medicine practice.},\n\tlanguage = {en},\n\turldate = {2020-07-07},\n\tbooktitle = {Artificial {Intelligence} in {Precision} {Health}},\n\tpublisher = {Academic Press},\n\tauthor = {Lugo Reyes, Saul Oswaldo},\n\teditor = {Barh, Debmalya},\n\tmonth = jan,\n\tyear = {2020},\n\tdoi = {10.1016/B978-0-12-817133-2.00021-5},\n\tkeywords = {Artificial intelligence, Differential diagnosis generators, Expert systems, Machine learning, Precision health},\n\tpages = {499--519},\n}\n\n

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\n \n\n \n \n \n \n \n Absence of FGFR3-TACC3 rearrangement in hematological malignancies with numerical chromosomal alteration.\n \n \n \n\n\n \n Banella, C.; Ginevrino, M.; Catalano, G.; Fabiani, E.; Falconi, G.; Divona, M.; Curzi, P.; Panetta, P.; Voso, M. T.; and Noguera, N. I.\n\n\n \n\n\n\n Hematology/Oncology and Stem Cell Therapy. March 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{banella_absence_2020,\n\ttitle = {Absence of {FGFR3}-{TACC3} rearrangement in hematological malignancies with numerical chromosomal alteration},\n\tissn = {1658-3876},\n\tdoi = {10.1016/j.hemonc.2020.02.005},\n\tabstract = {FGFR-TACC, found in different tumor types, is characterized by the fusion of a member of fibroblast grown factor receptor (FGFR) tyrosine kinase (TK) family to a member of the transforming acidic coiled-coil (TACC) proteins. Because chromosome numerical alterations, hallmarks of FGFR-TACC fusions are present in many hematological disorders and there are no data on the prevalence, we studied a series of patients with acute myeloid leukemia and myelodysplastic syndrome who presented numerical alterations using cytogenetic traditional analysis. None of the analyzed samples showed FGFR3-TACC3 gene fusion, so screening for this mutation at diagnosis is not recommended.},\n\tlanguage = {eng},\n\tjournal = {Hematology/Oncology and Stem Cell Therapy},\n\tauthor = {Banella, C. and Ginevrino, M. and Catalano, G. and Fabiani, E. and Falconi, G. and Divona, M. and Curzi, P. and Panetta, P. and Voso, M. T. and Noguera, N. I.},\n\tmonth = mar,\n\tyear = {2020},\n\tpmid = {32199932},\n\tkeywords = {Acute myeloid leukemia, Aneuploidy, FGFR3–TACC3, Glioblastoma, Myelodysplastic syndromes},\n}\n\n

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\n \n\n \n \n \n \n \n \n Mathematical Modeling of Tumors.\n \n \n \n \n\n\n \n Colin, T.\n\n\n \n\n\n\n In Nordlinger, B.; Villani, C.; and Rus, D., editor(s), Healthcare and Artificial Intelligence, pages 129–140. Springer International Publishing, Cham, March 2020.\n \n\n\n\n
\n\n\n\n \n \n $\"Mathematical$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@incollection{colin_mathematical_2020,\n\taddress = {Cham},\n\ttitle = {Mathematical {Modeling} of {Tumors}},\n\tisbn = {978-3-030-32161-1},\n\turl = {https://doi.org/10.1007/978-3-030-32161-1_18},\n\tabstract = {Mathematical modeling and scientific computing are part of the general scientific landscape and universally used in almost all industrial sectors. Car manufacturers use it to optimize their vehicles. In aeronautics, models and calculations are used to design aircraft. In energy, calculations can be used to explore extreme regimes (e.g., by simulating an accident in a nuclear power plant or a dam failure) that cannot of course be reached experimentally. Calculation can also be used to explain complex phenomena or to predict the future. This is the case in climatology.},\n\tlanguage = {en},\n\turldate = {2020-07-07},\n\tbooktitle = {Healthcare and {Artificial} {Intelligence}},\n\tpublisher = {Springer International Publishing},\n\tauthor = {Colin, Thierry},\n\teditor = {Nordlinger, Bernard and Villani, Cédric and Rus, Daniela},\n\tmonth = mar,\n\tyear = {2020},\n\tdoi = {10.1007/978-3-030-32161-1_18},\n\tpages = {129--140},\n}\n\n

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\n \n\n \n \n \n \n \n \n Artificial Intelligence Applied to Oncology.\n \n \n \n \n\n\n \n Blay, J.; Camblong, J.; and Sigaux, F.\n\n\n \n\n\n\n In Nordlinger, B.; Villani, C.; and Rus, D., editor(s), Healthcare and Artificial Intelligence, pages 185–197. Springer International Publishing, Cham, March 2020.\n \n\n\n\n
\n\n\n\n \n \n $\"Artificial$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@incollection{blay_artificial_2020,\n\taddress = {Cham},\n\ttitle = {Artificial {Intelligence} {Applied} to {Oncology}},\n\tisbn = {978-3-030-32161-1},\n\turl = {https://doi.org/10.1007/978-3-030-32161-1_24},\n\tabstract = {Western medicine is founded on the notion of medical evidence based on controlled clinical trials and the consensus of expert communities. This practice is robust and responds well to the needs of the so-called “average” patient. However, it lacks the tools and data to implement the recently established notion of precision medicine. Precision medicine in cancerology consists in taking into account the biological characteristics of patients and their tumors, the useful parameters of which are essentially currently provided by genomics and the rapid emergence of expression profiles of both cancer cells and immune cells. To implement such precision medicine practitioners must stay abreast and cope with knowledge of increasing scope and complexity in real time and optimize their analytical processes to take into account the large number of logical rules that quickly arise.},\n\tlanguage = {en},\n\turldate = {2020-07-07},\n\tbooktitle = {Healthcare and {Artificial} {Intelligence}},\n\tpublisher = {Springer International Publishing},\n\tauthor = {Blay, Jean-Yves and Camblong, Jurgi and Sigaux, François},\n\teditor = {Nordlinger, Bernard and Villani, Cédric and Rus, Daniela},\n\tmonth = mar,\n\tyear = {2020},\n\tdoi = {10.1007/978-3-030-32161-1_24},\n\tpages = {185--197},\n}\n\n

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\n \n\n \n \n \n \n \n \n New Compound Heterozygous Splice Site Mutations of the Skeletal Muscle Ryanodine Receptor (RYR1) Gene Manifest Fetal Akinesia: A Linkage with Congenital Myopathies.\n \n \n \n \n\n\n \n Zecevic, N.; Arsenijevic, V.; Manolakos, E.; Papoulidis, I.; Theocharis, G.; Sartsidis, A.; Tsagas, T.; Tziotis, I.; Dagklis, T.; Kalogeros, G.; Tsakiridis, I.; Stankovic, M. F.; and Eleftheriades, M.\n\n\n \n\n\n\n Molecular Syndromology, 11(2): 104–109. May 2020.\n Publisher: Karger Publishers\n\n\n\n
\n\n\n\n \n \n $\"New$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{zecevic_new_2020,\n\ttitle = {New {Compound} {Heterozygous} {Splice} {Site} {Mutations} of the {Skeletal} {Muscle} {Ryanodine} {Receptor} ({RYR1}) {Gene} {Manifest} {Fetal} {Akinesia}: {A} {Linkage} with {Congenital} {Myopathies}},\n\tvolume = {11},\n\tissn = {1661-8769, 1661-8777},\n\tshorttitle = {New {Compound} {Heterozygous} {Splice} {Site} {Mutations} of the {Skeletal} {Muscle} {Ryanodine} {Receptor} ({RYR1}) {Gene} {Manifest} {Fetal} {Akinesia}},\n\turl = {https://www.karger.com/Article/FullText/507034},\n\tdoi = {10.1159/000507034},\n\tabstract = {Mutations in the skeletal muscle ryanodine receptor (\\textit{RYR1}) gene have been linked to malignant hyperthermia susceptibility, central core disease, and minicore myopathy with external ophthalmoplegia. \\textit{RYR1} is an intracellular calcium release channel and plays a crucial role in the sarcoplasmic reticulum and transverse tubule connection. Here, we report 2 fetuses from the same parents with compound heterozygous mutations in the \\textit{RYR1} gene (c.10347+1G{\\textgreater}A and c.10456-2\\&\\#x0391;{\\textgreater}G) who presented with fetal akinesia and polyhydramnios at 27 and 19 weeks of gestation with intrauterine growth restriction in the third pregnancy. The prospective parents of the fetuses were heterozygous carriers for c.10456-2\\&\\#x0391;{\\textgreater}G (mother) and c.10347+1G{\\textgreater}A (father). Both mutations affect splice sites resulting in dysfunctional protein forms probably missing crucial domains of the C-terminus. Our findings reveal a new \\textit{RYR1} splice site mutation (c.10456-2\\&\\#x0391;{\\textgreater}G) that may be associated with the clinical features of myopathies, expanding the \\textit{RYR1} spectrum related to these pathologies.},\n\tlanguage = {english},\n\tnumber = {2},\n\turldate = {2020-07-06},\n\tjournal = {Molecular Syndromology},\n\tauthor = {Zecevic, Nebojsa and Arsenijevic, Vladimir and Manolakos, Emmanouil and Papoulidis, Ioannis and Theocharis, Georgios and Sartsidis, Anastasios and Tsagas, Tryfon and Tziotis, Ioannis and Dagklis, Themistoklis and Kalogeros, Georgios and Tsakiridis, Ioannis and Stankovic, Milica Filipovic and Eleftheriades, Makarios},\n\tmonth = may,\n\tyear = {2020},\n\tnote = {Publisher: Karger Publishers},\n\tpages = {104--109},\n}\n\n

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\n \n\n \n \n \n \n \n Thrombotic Risk Detection in Patients with Polycythemia Vera: The Predictive Role of DNMT3A/TET2/ASXL1 Mutations.\n \n \n \n\n\n \n Segura-Díaz, A.; Stuckey, R.; Florido, Y.; González-Martín, J. M.; López-Rodríguez, J. F.; Sánchez-Sosa, S.; González-Pérez, E.; Sáez Perdomo, M. N.; Perera, M. D. M.; de la Iglesia, S.; Molero-Labarta, T.; Gómez-Casares, M. T.; and Bilbao-Sieyro, C.\n\n\n \n\n\n\n Cancers, 12(4). April 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{segura-diaz_thrombotic_2020,\n\ttitle = {Thrombotic {Risk} {Detection} in {Patients} with {Polycythemia} {Vera}: {The} {Predictive} {Role} of {DNMT3A}/{TET2}/{ASXL1} {Mutations}},\n\tvolume = {12},\n\tissn = {2072-6694},\n\tshorttitle = {Thrombotic {Risk} {Detection} in {Patients} with {Polycythemia} {Vera}},\n\tdoi = {10.3390/cancers12040934},\n\tabstract = {The development of thrombotic events is common among patients with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). We studied the influence of pathogenic mutations frequently associated with myeloid malignancies on thrombotic events using next-generation sequencing (NGS) in an initial cohort of 68 patients with myeloproliferative neoplasms (MPN). As expected, the presence of mutations in DNMT3A, TET2, and ASXL1 (DTA genes) was positively associated with age for the whole cohort (p = 0.025, OR: 1.047, 95\\% CI: 1.006-1.090). Also, while not related with events in the whole cohort, DTA mutations were strongly associated with the development of vascular events in PV patients (p = 0.028). To confirm the possible association between the presence of DTA mutation and thrombotic events, we performed a case-control study on 55 age-matched patients with PV (including 12 PV patients from the initial cohort, 25 with event vs. 30 no event). In the age-matched case-control PV cohort, the presence of ≥1 DTA mutation significantly increased the risk of a thrombotic event (OR: 6.333, p = 0.0024). Specifically, mutations in TET2 were associated with thrombotic events in the PV case-control cohort (OR: 3.56, 95\\% CI: 1.15-11.83, p = 0.031). Our results suggest that pathogenic DTA mutations, and particularly TET2 mutations, may be an independent risk factor for thrombosis in patients with PV. However, the predictive value of TET2 and DTA mutations in ET and PMF was inconclusive and should be determined in a larger cohort.},\n\tlanguage = {eng},\n\tnumber = {4},\n\tjournal = {Cancers},\n\tauthor = {Segura-Díaz, Adrián and Stuckey, Ruth and Florido, Yanira and González-Martín, Jesús María and López-Rodríguez, Juan Francisco and Sánchez-Sosa, Santiago and González-Pérez, Elena and Sáez Perdomo, María Nieves and Perera, María Del Mar and de la Iglesia, Silvia and Molero-Labarta, Teresa and Gómez-Casares, María Teresa and Bilbao-Sieyro, Cristina},\n\tmonth = apr,\n\tyear = {2020},\n\tpmid = {32290079},\n\tpmcid = {PMC7226609},\n\tkeywords = {cardiovascular disease, myeloproliferative neoplasms, next-generation sequencing, personalized medicine, prognosis, thrombosis},\n}\n\n

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\n \n\n \n \n \n \n \n Molecular Diagnostic of Solid Tumor Using a Next Generation Sequencing Custom-Designed Multi-Gene Panel.\n \n \n \n\n\n \n de Biase, D.; Acquaviva, G.; Visani, M.; Sanza, V.; Argento, C. M.; De Leo, A.; Maloberti, T.; Pession, A.; and Tallini, G.\n\n\n \n\n\n\n Diagnostics (Basel, Switzerland), 10(4). April 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{de_biase_molecular_2020,\n\ttitle = {Molecular {Diagnostic} of {Solid} {Tumor} {Using} a {Next} {Generation} {Sequencing} {Custom}-{Designed} {Multi}-{Gene} {Panel}},\n\tvolume = {10},\n\tissn = {2075-4418},\n\tdoi = {10.3390/diagnostics10040250},\n\tabstract = {Next generation sequencing (NGS) allows parallel sequencing of multiple genes at a very high depth of coverage. The need to analyze a variety of targets for diagnostic/prognostic/predictive purposes requires multi-gene characterization. Multi-gene panels are becoming standard approaches for the molecular analysis of solid lesions. We report a custom-designed 128 multi-gene panel engineered to cover the relevant targets in 22 oncogene/oncosuppressor genes for the analysis of the solid tumors most frequently subjected to routine genotyping. A total of 1695 solid tumors were analyzed for panel validation. The analytical sensitivity is 5\\%. Analytical validation: (i) Accuracy: sequencing results obtained using the multi-gene panel are concordant using two different NGS platforms and single-gene approach sequencing (100\\% of 83 cases); (ii) Precision: consistent results are obtained in the samples analyzed twice with the same platform (100\\% of 20 cases). Clinical validation: the frequency of mutations identified in different tumor types is consistent with the published literature. This custom-designed multi-gene panel allows to analyze with high sensitivity and throughput 22 oncogenes/oncosuppressor genes involved in diagnostic/prognostic/predictive characterization of central nervous system tumors, non-small-cell lung carcinomas, colorectal carcinomas, thyroid nodules, pancreatic lesions, melanoma, oral squamous carcinomas and gastrointestinal stromal tumors.},\n\tlanguage = {eng},\n\tnumber = {4},\n\tjournal = {Diagnostics (Basel, Switzerland)},\n\tauthor = {de Biase, Dario and Acquaviva, Giorgia and Visani, Michela and Sanza, Viviana and Argento, Chiara M. and De Leo, Antonio and Maloberti, Thais and Pession, Annalisa and Tallini, Giovanni},\n\tmonth = apr,\n\tyear = {2020},\n\tpmid = {32340363},\n\tpmcid = {PMC7236002},\n\tkeywords = {multi-gene custom panel, mutational analysis, next generation sequencing, solid tumor},\n}\n\n

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\n \n\n \n \n \n \n \n Familial screening in case of acute myocarditis reveals inherited arrhythmogenic left ventricular cardiomyopathies.\n \n \n \n\n\n \n Piriou, N.; Marteau, L.; Kyndt, F.; Serfaty, J. M.; Toquet, C.; Le Gloan, L.; Warin-Fresse, K.; Guijarro, D.; Le Tourneau, T.; Conan, E.; Thollet, A.; Probst, V.; and Trochu, J.\n\n\n \n\n\n\n ESC heart failure. May 2020.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{piriou_familial_2020,\n\ttitle = {Familial screening in case of acute myocarditis reveals inherited arrhythmogenic left ventricular cardiomyopathies},\n\tissn = {2055-5822},\n\tdoi = {10.1002/ehf2.12686},\n\tabstract = {AIMS: Several data suggest that acute myocarditis could be related to genetic variants involved in familial cardiomyopathies, particularly arrhythmogenic cardiomyopathy, but the management of patients with acute myocarditis and their families regarding their risk for having an associated inherited cardiomyopathy is unclear.\nMETHODS AND RESULTS: Families with at least one individual with a documented episode of acute myocarditis and at least one individual with a cardiomyopathy or a history of sudden death were included in the study. Comprehensive pedigree, including genetic testing, and history of these families were analysed. Six families were included. Genetic analysis revealed a variant in desmosomal proteins genes in all the probands [five in desmoplakin (DSP) gene and one in desmoglein 2 gene]. In the five families identified with a DSP variant, genetic testing was triggered by the association of an acute myocarditis with a single case of apparently isolated dilated cardiomyopathy or sudden death. Familial screening identified 28 DSP variant carriers; 39\\% had an arrhythmogenic left ventricular (LV) cardiomyopathy phenotype. Familial histories of sudden death were frequent, and a remarkable phenotype of isolated LV late gadolinium enhancement on contrast-enhanced cardiac magnetic resonance without any other structural abnormality was found in 38\\% of asymptomatic mutation carriers. None of the DSP variant carriers had imaging characteristics of right ventricle involvement meeting current Task Force criteria for arrhythmogenic right ventricular cardiomyopathy.\nCONCLUSIONS: Comprehensive familial screening including genetic testing in case of acute myocarditis associated with a family history of cardiomyopathy or sudden death revealed unknown or misdiagnosed arrhythmogenic variant carriers with left-dominant phenotypes that frequently evade arrhythmogenic right ventricular cardiomyopathy Task Force criteria. In view of our results, acute myocarditis should be considered as an additional criterion for arrhythmogenic cardiomyopathy, and genetic testing should be advised in patients who experience acute myocarditis and have a family history of cardiomyopathy or sudden death.},\n\tlanguage = {eng},\n\tjournal = {ESC heart failure},\n\tauthor = {Piriou, Nicolas and Marteau, Lara and Kyndt, Florence and Serfaty, Jean Michel and Toquet, Claire and Le Gloan, Laurianne and Warin-Fresse, Karine and Guijarro, Damien and Le Tourneau, Thierry and Conan, Emilie and Thollet, Aurélie and Probst, Vincent and Trochu, Jean-Noël},\n\tmonth = may,\n\tyear = {2020},\n\tpmid = {32356610},\n\tkeywords = {Arrhythmogenic cardiomyopathy, Genetics, Myocarditis},\n}\n\n

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\n AIMS: Several data suggest that acute myocarditis could be related to genetic variants involved in familial cardiomyopathies, particularly arrhythmogenic cardiomyopathy, but the management of patients with acute myocarditis and their families regarding their risk for having an associated inherited cardiomyopathy is unclear. METHODS AND RESULTS: Families with at least one individual with a documented episode of acute myocarditis and at least one individual with a cardiomyopathy or a history of sudden death were included in the study. Comprehensive pedigree, including genetic testing, and history of these families were analysed. Six families were included. Genetic analysis revealed a variant in desmosomal proteins genes in all the probands [five in desmoplakin (DSP) gene and one in desmoglein 2 gene]. In the five families identified with a DSP variant, genetic testing was triggered by the association of an acute myocarditis with a single case of apparently isolated dilated cardiomyopathy or sudden death. Familial screening identified 28 DSP variant carriers; 39% had an arrhythmogenic left ventricular (LV) cardiomyopathy phenotype. Familial histories of sudden death were frequent, and a remarkable phenotype of isolated LV late gadolinium enhancement on contrast-enhanced cardiac magnetic resonance without any other structural abnormality was found in 38% of asymptomatic mutation carriers. None of the DSP variant carriers had imaging characteristics of right ventricle involvement meeting current Task Force criteria for arrhythmogenic right ventricular cardiomyopathy. CONCLUSIONS: Comprehensive familial screening including genetic testing in case of acute myocarditis associated with a family history of cardiomyopathy or sudden death revealed unknown or misdiagnosed arrhythmogenic variant carriers with left-dominant phenotypes that frequently evade arrhythmogenic right ventricular cardiomyopathy Task Force criteria. In view of our results, acute myocarditis should be considered as an additional criterion for arrhythmogenic cardiomyopathy, and genetic testing should be advised in patients who experience acute myocarditis and have a family history of cardiomyopathy or sudden death.\n

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\n \n\n \n \n \n \n \n \n Early assessment of KRAS mutation in cfDNA correlates with risk of progression and death in advanced non-small-cell lung cancer.\n \n \n \n \n\n\n \n Zulato, E.; Attili, I.; Pavan, A.; Nardo, G.; Del Bianco, P.; Boscolo Bragadin, A.; Verza, M.; Pasqualini, L.; Pasello, G.; Fassan, M.; Calabrese, F.; Guarneri, V.; Amadori, A.; Conte, P.; Indraccolo, S.; and Bonanno, L.\n\n\n \n\n\n\n British Journal of Cancer, 123(1): 81–91. May 2020.\n Number: 1 Publisher: Nature Publishing Group\n\n\n\n
\n\n\n\n \n \n $\"Early$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{zulato_early_2020,\n\ttitle = {Early assessment of {KRAS} mutation in {cfDNA} correlates with risk of progression and death in advanced non-small-cell lung cancer},\n\tvolume = {123},\n\tcopyright = {2020 The Author(s), under exclusive licence to Cancer Research UK},\n\tissn = {1532-1827},\n\turl = {https://www.nature.com/articles/s41416-020-0833-7},\n\tdoi = {10.1038/s41416-020-0833-7},\n\tabstract = {Liquid biopsy has the potential to monitor biological effects of treatment. KRAS represents the most commonly mutated oncogene in Caucasian non-small-cell lung cancer (NSCLC). The aim of this study was to explore association of dynamic plasma KRAS genotyping with outcome in advanced NSCLC patients.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2020-07-06},\n\tjournal = {British Journal of Cancer},\n\tauthor = {Zulato, Elisabetta and Attili, Ilaria and Pavan, Alberto and Nardo, Giorgia and Del Bianco, Paola and Boscolo Bragadin, Andrea and Verza, Martina and Pasqualini, Lorenza and Pasello, Giulia and Fassan, Matteo and Calabrese, Fiorella and Guarneri, Valentina and Amadori, Alberto and Conte, PierFranco and Indraccolo, Stefano and Bonanno, Laura},\n\tmonth = may,\n\tyear = {2020},\n\tnote = {Number: 1\nPublisher: Nature Publishing Group},\n\tpages = {81--91},\n}\n\n

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\n \n\n \n \n \n \n \n \n Expression of GNAS, TP53, and PTEN Improves the Patient Prognostication in Sonic Hedgehog (SHH) Medulloblastoma Subgroup.\n \n \n \n \n\n\n \n Silva, L. S. d.; Mançano, B. M.; Paula, F. E. d.; Reis, M. B. d.; Almeida, G. C. d.; Matsushita, M.; Junior, C. A.; Evangelista, A. F.; Saggioro, F.; Serafini, L. N.; Stavale, J. N.; Malheiros, S. M. F.; Lima, M.; Hajj, G. N. M.; Lima, M. A. d.; Taylor, M. D.; Leal, L. F.; and Reis, R. M.\n\n\n \n\n\n\n The Journal of Molecular Diagnostics, 22(7): 957–966. July 2020.\n Publisher: Elsevier\n\n\n\n
\n\n\n\n \n \n $\"Expression$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{silva_expression_2020,\n\ttitle = {Expression of {GNAS}, {TP53}, and {PTEN} {Improves} the {Patient} {Prognostication} in {Sonic} {Hedgehog} ({SHH}) {Medulloblastoma} {Subgroup}},\n\tvolume = {22},\n\tissn = {1525-1578},\n\turl = {https://jmd.amjpathol.org/article/S1525-1578(20)30301-9/abstract},\n\tdoi = {10.1016/j.jmoldx.2020.04.207},\n\tabstract = {{\\textless}p{\\textgreater}Medulloblastoma (MB) is the most common malignant brain tumor in children. It is currently classified in four main molecular subgroups with different clinical outcomes: sonic hedgehog, wingless, group 3, and group 4 (MB$_{\\textrm{SHH}}$, MB$_{\\textrm{WNT}}$, MB$_{\\textrm{GRP3}}$, or MB$_{\\textrm{GRP4}}$). Presently, a 22-gene expression panel has been efficiently applied for molecular subgrouping using nCounter technology. In this study, formalin-fixed, paraffin-embedded samples from 164 Brazilian medulloblastomas were evaluated, applying the 22-gene panel, and subclassified into the low and high expression of nine key medulloblastoma-related genes. In addition, \\textit{TP53} mutation status was assessed using TruSight Tumor 15 Panel, and its correlation with expression and prognostic impact was evaluated. Samples from 149 of 164 patients (90\\%) were classified into MB$_{\\textrm{SHH}}$ (47.7\\%), MB$_{\\textrm{WNT}}$ (16.1\\%), MB$_{\\textrm{GRP3}}$ (15.4\\%), and MB$_{\\textrm{GRP4}}$ (20.8\\%). \\textit{GNAS} presented the highest expression levels, with higher expression in MB$_{\\textrm{SHH}}$. \\textit{TP53}, \\textit{MYCN}, \\textit{SOX2}, and \\textit{MET} were also up-regulated in MB$_{\\textrm{SHH}}$, whereas \\textit{PTEN} was up-regulated in MB$_{\\textrm{GRP4}}$. \\textit{GNAS}, \\textit{TP53}, and \\textit{PTEN} low expression was associated with the unfavorable patient outcome only for MB$_{\\textrm{SHH}}$ (\\textit{P} = 0.04, \\textit{P} = 0.01, and \\textit{P} = 0.02, respectively). \\textit{TP53} mutations were detected in 28.57\\% of MB$_{\\textrm{SHH}}$ cases and exhibited association with lower expression and worse clinical outcome, although not statistically significant. The 22-gene panel for molecular classification of medulloblastoma associated with the expression of \\textit{GNAS}, \\textit{TP53}, and \\textit{PTEN} improves the patient prognostication in MB$_{\\textrm{SHH}}$ subgroup and can be easily incorporated in the 22-gene panel without any additional costs.{\\textless}/p{\\textgreater}},\n\tlanguage = {English},\n\tnumber = {7},\n\turldate = {2020-07-06},\n\tjournal = {The Journal of Molecular Diagnostics},\n\tauthor = {Silva, Luciane S. da and Mançano, Bruna M. and Paula, Flávia E. de and Reis, Mariana B. dos and Almeida, Gisele C. de and Matsushita, Marcus and Junior, Carlos A. and Evangelista, Adriane F. and Saggioro, Fabiano and Serafini, Luciano N. and Stavale, João N. and Malheiros, Suzana M. F. and Lima, Matheus and Hajj, Glaucia N. M. and Lima, Marcos A. de and Taylor, Michael D. and Leal, Letícia F. and Reis, Rui M.},\n\tmonth = jul,\n\tyear = {2020},\n\tpmid = {32380172},\n\tnote = {Publisher: Elsevier},\n\tpages = {957--966},\n}\n\n

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\n \n\n \n \n \n \n \n \n Genetic Profiling of Advanced Melanoma: Candidate Mutations for Predicting Sensitivity and Resistance to Targeted Therapy.\n \n \n \n \n\n\n \n Olbryt, M.; Pigłowski, W.; Rajczykowski, M.; Pfeifer, A.; Student, S.; and Fiszer-Kierzkowska, A.\n\n\n \n\n\n\n Targeted Oncology. January 2020.\n \n\n\n\n
\n\n\n\n \n \n $\"Genetic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{olbryt_genetic_2020,\n\ttitle = {Genetic {Profiling} of {Advanced} {Melanoma}: {Candidate} {Mutations} for {Predicting} {Sensitivity} and {Resistance} to {Targeted} {Therapy}},\n\tissn = {1776-260X},\n\tshorttitle = {Genetic {Profiling} of {Advanced} {Melanoma}},\n\turl = {https://doi.org/10.1007/s11523-020-00695-0},\n\tdoi = {10.1007/s11523-020-00695-0},\n\tlanguage = {en},\n\turldate = {2020-02-11},\n\tjournal = {Targeted Oncology},\n\tauthor = {Olbryt, Magdalena and Pigłowski, Wojciech and Rajczykowski, Marcin and Pfeifer, Aleksandra and Student, Sebastian and Fiszer-Kierzkowska, Anna},\n\tmonth = jan,\n\tyear = {2020},\n\tkeywords = {Alamut, CNV, FFPE, Genomics, INDEL, SNV, SOPHiA DDM, Solid Tumor},\n}\n\n

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\n \n\n \n \n \n \n \n \n A Novel Homozygous Mutation in CYP11A1 Gene is Associated with Severe Adrenal Insufficiency in 46, XX Patient.\n \n \n \n \n\n\n \n Kara, O.; Gorukmez, O.; Ekici, A.; and Celik, F.\n\n\n \n\n\n\n Fetal and Pediatric Pathology,1–5. January 2020.\n \n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{kara_novel_2020,\n\ttitle = {A {Novel} {Homozygous} {Mutation} in {CYP11A1} {Gene} is {Associated} with {Severe} {Adrenal} {Insufficiency} in 46, {XX} {Patient}},\n\turl = {https://www.tandfonline.com/doi/abs/10.1080/15513815.2020.1716901},\n\tdoi = {10.1080/15513815.2020.1716901},\n\tjournal = {Fetal and Pediatric Pathology},\n\tauthor = {Kara, Ozlem and Gorukmez, Orhan and Ekici, Arzu and Celik, Fatih},\n\tmonth = jan,\n\tyear = {2020},\n\tkeywords = {CES, Case Study, Commercial, Exome, Genomics, Hereditary Disorders, Illumina Sequencer, Large panel, Rare disease},\n\tpages = {1--5},\n}\n\n

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\n \n\n \n \n \n \n \n \n Artificial Intelligence in Precision Health: From Concept to Applications.\n \n \n \n \n\n\n \n Barh, D.\n\n\n \n\n\n\n Academic Press, March 2020.\n \n\n\n\n
\n\n\n\n \n \n $\"Artificial$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@book{barh_artificial_2020,\n\ttitle = {Artificial {Intelligence} in {Precision} {Health}: {From} {Concept} to {Applications}},\n\tisbn = {0-12-817338-6},\n\turl = {https://www.elsevier.com/books/artificial-intelligence-in-precision-health/barh/978-0-12-817133-2},\n\tpublisher = {Academic Press},\n\tauthor = {Barh, Debmalya},\n\tmonth = mar,\n\tyear = {2020},\n}\n\n

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\n \n\n \n \n \n \n \n \n A Novel Homozygous Variant in the Fork-Head-Associated Domain of Polynucleotide Kinase Phosphatase in a Patient Affected by Late-Onset Ataxia With Oculomotor Apraxia Type 4.\n \n \n \n \n\n\n \n Campopiano, R.; Ferese, R.; Buttari, F.; Femiano, C.; Centonze, D.; Fornai, F.; Biagioni, F.; Chiaravalloti, M. A.; Magnani, M.; and Giardina, E.\n\n\n \n\n\n\n Frontiers in Neurology, 10. January 2020.\n \n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{campopiano_novel_2020,\n\ttitle = {A {Novel} {Homozygous} {Variant} in the {Fork}-{Head}-{Associated} {Domain} of {Polynucleotide} {Kinase} {Phosphatase} in a {Patient} {Affected} by {Late}-{Onset} {Ataxia} {With} {Oculomotor} {Apraxia} {Type} 4},\n\tvolume = {10},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974581/},\n\tdoi = {https://doi.org/10.3389/fneur.2019.01331},\n\tjournal = {Frontiers in Neurology},\n\tauthor = {Campopiano, Rosa and Ferese, Rosangela and Buttari, Fabio and Femiano, Cinzia and Centonze, Diego and Fornai, Francesco and Biagioni, Francesca and Chiaravalloti, Maria Antonietta and Magnani, Mauro and Giardina, Emiliano},\n\tmonth = jan,\n\tyear = {2020},\n\tkeywords = {CES, Illumina Sequencer, Large panel, SOPHiA DDM},\n}\n\n

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\n \n\n \n \n \n \n \n \n A novel variant of RyR2 gene in a family misdiagnosed as congenital long QT syndrome: The importance of genetic testing.\n \n \n \n \n\n\n \n Letsas, K. P.; Prappa, E.; Bazoukis, G.; Lioni, L.; Pantou, M. P.; Gourzi, P.; Degiannis, D.; and Sideris, A.\n\n\n \n\n\n\n Journal of Electrocardiology. March 2020.\n \n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{letsas_novel_2020,\n\ttitle = {A novel variant of {RyR2} gene in a family misdiagnosed as congenital long {QT} syndrome: {The} importance of genetic testing},\n\tissn = {0022-0736},\n\tshorttitle = {A novel variant of {RyR2} gene in a family misdiagnosed as congenital long {QT} syndrome},\n\turl = {http://www.sciencedirect.com/science/article/pii/S0022073620301096},\n\tdoi = {10.1016/j.jelectrocard.2020.03.001},\n\tabstract = {Catecholaminergic polymorphic ventricular tachycardia (CPVT) and Long-QT syndrome (LQTS) are two distinct entities with similar clinical presentation and management but different clinical course. In this study, we present two family members presented with aborted sudden cardiac death that was attributed to CPVT. The CPVT may be underrecognized in SCD victims and a diagnosis of “atypical LQTS” may warrant consideration of CPVT and analysis of RyR2 if the standard cardiac channel gene screen for LQTS is negative. Although the management of both channelopathies is quite common the clinical outcomes are different, with CPVT displaying a more malignant clinical course.},\n\tlanguage = {en},\n\turldate = {2020-03-11},\n\tjournal = {Journal of Electrocardiology},\n\tauthor = {Letsas, Konstantinos P. and Prappa, Efstathia and Bazoukis, George and Lioni, Louiza and Pantou, Malena P. and Gourzi, Polyxeni and Degiannis, Dimitrios and Sideris, Antonios},\n\tmonth = mar,\n\tyear = {2020},\n\tkeywords = {Cardiac arrest, Catecholaminergic polymorphic ventricular tachycardia, Channelopathies, Long-QT syndrome},\n}\n\n

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\n \n\n \n \n \n \n \n \n Genetic Susceptibility Determines β-Cell Function and Fasting Glycemia Trajectories Throughout Childhood: A 12-Year Cohort Study (EarlyBird 76).\n \n \n \n \n\n\n \n Carayol, J.; Hosking, J.; Pinkney, J.; Marquis, J.; Charpagne, A.; Metairon, S.; Jeffery, A.; Hager, J.; and Martin, F.\n\n\n \n\n\n\n Diabetes Care. January 2020.\n \n\n\n\n
\n\n\n\n \n \n $\"Genetic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{carayol_genetic_2020,\n\ttitle = {Genetic {Susceptibility} {Determines} β-{Cell} {Function} and {Fasting} {Glycemia} {Trajectories} {Throughout} {Childhood}: {A} 12-{Year} {Cohort} {Study} ({EarlyBird} 76)},\n\tcopyright = {© 2020 by the American Diabetes Association.. http://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.},\n\tissn = {0149-5992, 1935-5548},\n\tshorttitle = {Genetic {Susceptibility} {Determines} β-{Cell} {Function} and {Fasting} {Glycemia} {Trajectories} {Throughout} {Childhood}},\n\turl = {https://care.diabetesjournals.org/content/early/2020/01/02/dc19-0806},\n\tdoi = {10.2337/dc19-0806},\n\tlanguage = {en},\n\turldate = {2020-02-11},\n\tjournal = {Diabetes Care},\n\tauthor = {Carayol, Jerome and Hosking, Joanne and Pinkney, Jonathan and Marquis, Julien and Charpagne, Aline and Metairon, Sylviane and Jeffery, Alison and Hager, Jörg and Martin, Francois-Pierre},\n\tmonth = jan,\n\tyear = {2020},\n\tpmid = {31915205},\n}\n\n

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\n \n 2019\n \n \n (61)\n \n \n

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\n \n\n \n \n \n \n \n \n Assessing synthetic spike-in controls with hybrid captured-based somatic variant sequencing.\n \n \n \n \n\n\n \n Green, D.; Deharvengt, S.; Morrison, T.; Tsongalis, G.; and Lefferts, J.\n\n\n \n\n\n\n Cancer Genetics, 233: S16–S17. April 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Assessing$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{green_assessing_2019,\n\ttitle = {Assessing synthetic spike-in controls with hybrid captured-based somatic variant sequencing},\n\tvolume = {233},\n\turl = {https://www.cancergeneticsjournal.org/article/S2210-7762(19)30203-0/fulltext},\n\tjournal = {Cancer Genetics},\n\tauthor = {Green, Donald and Deharvengt, Sophie and Morrison, Thomas and Tsongalis, Gregory and Lefferts, Joel},\n\tmonth = apr,\n\tyear = {2019},\n\tkeywords = {FFPE, Genomics, TST170},\n\tpages = {S16--S17},\n}\n\n

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\n \n\n \n \n \n \n \n \n Comparison of third-party NGS pipelines using control material.\n \n \n \n \n\n\n \n Green, D.; Deharvengt, S.; Tsongalis, G.; and Lefferts, J.\n\n\n \n\n\n\n Cancer Genetics, 233: S17. April 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Comparison$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 4 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{green_comparison_2019,\n\ttitle = {Comparison of third-party {NGS} pipelines using control material},\n\tvolume = {233},\n\turl = {https://www.cancergeneticsjournal.org/article/S2210-7762(19)30204-2/fulltext},\n\tjournal = {Cancer Genetics},\n\tauthor = {Green, Donald and Deharvengt, Sophie and Tsongalis, Gregory and Lefferts, Joel},\n\tmonth = apr,\n\tyear = {2019},\n\tpages = {S17},\n}\n\n

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\n \n\n \n \n \n \n \n \n Considerations for implementation of the new ASCO/CAP guidelines for HER2 testing in the clinical laboratory.\n \n \n \n \n\n\n \n Haskell, G.; Glotzbach, C.; Faulk, S.; Sanders-Cliette, A.; Attis, M. G.; Schwartz, S.; and Tepperberg, J.\n\n\n \n\n\n\n Cancer Genetics, 233: S17–S18. April 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Considerations$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{haskell_considerations_2019,\n\ttitle = {Considerations for implementation of the new {ASCO}/{CAP} guidelines for {HER2} testing in the clinical laboratory},\n\tvolume = {233},\n\turl = {https://www.cancergeneticsjournal.org/article/S2210-7762(19)30206-6/fulltext},\n\tjournal = {Cancer Genetics},\n\tauthor = {Haskell, Gloria and Glotzbach, Caron and Faulk, Sonya and Sanders-Cliette, Angela and Attis, Maria Gallego and Schwartz, Stuart and Tepperberg, Jim},\n\tmonth = apr,\n\tyear = {2019},\n\tkeywords = {CNV, Genomics, INDEL, RNA, SNV, SOPHiA DDM, Solid Tumor, TST170},\n\tpages = {S17--S18},\n}\n\n

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\n \n\n \n \n \n \n \n \n Conference: Electronic Posters.\n \n \n \n \n\n\n \n McGinn, D. E.; Unolt, M.; Crowley, T. B.; Emanuel, B. S.; Zackai, E. H.; Moss, E.; Morrow, B.; Nowakowska, B.; Vermeesch, J.; and Swillen, A.\n\n\n \n\n\n\n European Journal of Human Genetics, 27: 870–1041. July 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Conference:$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{mcginn_conference_2019,\n\ttitle = {Conference: {Electronic} {Posters}},\n\tvolume = {27},\n\tshorttitle = {Conference},\n\turl = {https://www.nature.com/articles/s41431-019-0408-3},\n\tjournal = {European Journal of Human Genetics},\n\tauthor = {McGinn, D. E. and Unolt, M. and Crowley, T. B. and Emanuel, B. S. and Zackai, E. H. and Moss, E. and Morrow, B. and Nowakowska, B. and Vermeesch, J. and Swillen, A.},\n\tmonth = jul,\n\tyear = {2019},\n\tkeywords = {Abstract, CES, Case Study, Exome, Genomics, Nephropathies, PKD1, SOPHiA DDM, VUS},\n\tpages = {870--1041},\n}\n\n

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\n \n\n \n \n \n \n \n \n Integrated routine workflow using next-generation sequencing and a fully-automated platform for the detection of KRAS, NRAS and BRAF mutations in formalin-fixed paraffin embedded samples with poor DNA quality in patients with colorectal carcinoma.\n \n \n \n \n\n\n \n Franczak, C.; Dubouis, L.; Gilson, P.; Husson, M.; Rouyer, M.; Demange, J.; Leroux, A.; Merlin, J.; and Harle, A.\n\n\n \n\n\n\n PloS one, 14(2). February 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Integrated$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{franczak_integrated_2019,\n\ttitle = {Integrated routine workflow using next-generation sequencing and a fully-automated platform for the detection of {KRAS}, {NRAS} and {BRAF} mutations in formalin-fixed paraffin embedded samples with poor {DNA} quality in patients with colorectal carcinoma},\n\tvolume = {14},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392303/},\n\tnumber = {2},\n\tjournal = {PloS one},\n\tauthor = {Franczak, Claire and Dubouis, Ludovic and Gilson, Pauline and Husson, Marie and Rouyer, Marie and Demange, Jessica and Leroux, Agnès and Merlin, Jean-Louis and Harle, Alexandre},\n\tmonth = feb,\n\tyear = {2019},\n\tkeywords = {BRAF, Cancer, FFPE, Genomics, KRAS, NRAS, SOPHiA DDM, Solid Tumor, Targeted},\n}\n\n

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\n \n\n \n \n \n \n \n \n Multigene panel testing for hereditary breast cancer: An analysis of 70 BRCA-negative Turkish patients.\n \n \n \n \n\n\n \n Erdem, H. B.; and Bahsi, T.\n\n\n \n\n\n\n Cumhuriyet Tıp Dergisi, 41(3): 569–575. September 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Multigene$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{erdem_multigene_2019,\n\ttitle = {Multigene panel testing for hereditary breast cancer: {An} analysis of 70 {BRCA}-negative {Turkish} patients},\n\tvolume = {41},\n\tshorttitle = {Multigene panel testing for hereditary breast cancer},\n\turl = {https://dergipark.org.tr/en/pub/cmj/issue/49151/623656},\n\tnumber = {3},\n\tjournal = {Cumhuriyet Tıp Dergisi},\n\tauthor = {Erdem, Haktan Bağış and Bahsi, Taha},\n\tmonth = sep,\n\tyear = {2019},\n\tkeywords = {BRCA1, BRCA1/2, BRCA2, Blood, Genomics, HCS, Hereditary Breast Cancer, Hereditary Disorders, SOPHiA DDM, Targeted},\n\tpages = {569--575},\n}\n\n

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\n \n\n \n \n \n \n \n \n New germline BRCA2 gene variant in the Tuvinian Mongol breast cancer patients.\n \n \n \n \n\n\n \n Gervas, P.; Klyuch, B.; Denisov, E.; Kiselev, A.; Molokov, A.; Pisareva, L.; Malinovskaya, E.; Choynzonov, E.; and Cherdyntseva, N.\n\n\n \n\n\n\n Molecular biology reports, 46(5): 5537–5541. July 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"New$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{gervas_new_2019,\n\ttitle = {New germline {BRCA2} gene variant in the {Tuvinian} {Mongol} breast cancer patients},\n\tvolume = {46},\n\turl = {https://link.springer.com/article/10.1007/s11033-019-04928-y},\n\tnumber = {5},\n\tjournal = {Molecular biology reports},\n\tauthor = {Gervas, Polina and Klyuch, Boris and Denisov, Evgeny and Kiselev, Artem and Molokov, Alexey and Pisareva, Lubov and Malinovskaya, Elena and Choynzonov, Evgeny and Cherdyntseva, Nadezda},\n\tmonth = jul,\n\tyear = {2019},\n\tkeywords = {BRCA2, Blood, Case Study, Genomics, HCS, Hereditary Disorders, INDEL, Illumina Sequencer, SOPHiA DDM, Targeted},\n\tpages = {5537--5541},\n}\n\n

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\n \n\n \n \n \n \n \n \n Spanish Guidelines for the use of targeted deep sequencing in myelodysplastic syndromes and chronic myelomonocytic leukaemia.\n \n \n \n \n\n\n \n Palomo, L.; Ibáñez, M.; Abáigar, M.; Vázquez, I.; Álvarez, S.; Cabezón, M.; Tazón-Vega, B.; Rapado, I.; Fuster-Tormo, F.; and Cervera, J.\n\n\n \n\n\n\n British Journal of Haematology. October 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Spanish$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{palomo_spanish_2019,\n\ttitle = {Spanish {Guidelines} for the use of targeted deep sequencing in myelodysplastic syndromes and chronic myelomonocytic leukaemia},\n\turl = {https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.16175},\n\tjournal = {British Journal of Haematology},\n\tauthor = {Palomo, Laura and Ibáñez, Mariam and Abáigar, María and Vázquez, Iria and Álvarez, Sara and Cabezón, Marta and Tazón-Vega, Bárbara and Rapado, Inmaculada and Fuster-Tormo, Francisco and Cervera, José},\n\tmonth = oct,\n\tyear = {2019},\n\tkeywords = {Blood, CMML, CNV, Chronic Myelomonocytic Leukemia, Genomics, Guidelines, Liquid tumor, MDS, Myelodysplastic syndromes, SNV, SOPHiA DDM, Targeted},\n}\n\n

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\n \n\n \n \n \n \n \n \n The same mutation in a family with adenosine deaminase 2 deficiency.\n \n \n \n \n\n\n \n Sozeri, B.; Ercan, G.; Dogan, O. A.; Yıldız, J.; Demir, F.; and Doğanay, L.\n\n\n \n\n\n\n Rheumatology international,1–7. September 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"The$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{sozeri_same_2019,\n\ttitle = {The same mutation in a family with adenosine deaminase 2 deficiency},\n\turl = {https://link.springer.com/article/10.1007/s00296-019-04444-z},\n\tjournal = {Rheumatology international},\n\tauthor = {Sozeri, Betul and Ercan, Gozde and Dogan, Ozlem Akgun and Yıldız, Jale and Demir, Ferhat and Doğanay, Levent},\n\tmonth = sep,\n\tyear = {2019},\n\tkeywords = {ADA2, Adenosine Deaminase 2 Deficiency, Blood, Case Study, Genomics, Rare disease, SOPHiA DDM},\n\tpages = {1--7},\n}\n\n

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\n \n\n \n \n \n \n \n \n Uncommon mutational profiles of metastatic colorectal cancer detected during routine genotyping using next generation sequencing.\n \n \n \n \n\n\n \n Franczak, C.; Kandathil, S. M.; Gilson, P.; Husson, M.; Rouyer, M.; Demange, J.; Leroux, A.; Merlin, J.; and Harlé, A.\n\n\n \n\n\n\n Scientific reports, 9(1): 1–8. May 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Uncommon$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{franczak_uncommon_2019,\n\ttitle = {Uncommon mutational profiles of metastatic colorectal cancer detected during routine genotyping using next generation sequencing},\n\tvolume = {9},\n\turl = {https://www.nature.com/articles/s41598-019-43646-0},\n\tnumber = {1},\n\tjournal = {Scientific reports},\n\tauthor = {Franczak, Claire and Kandathil, Shaun M. and Gilson, Pauline and Husson, Marie and Rouyer, Marie and Demange, Jessica and Leroux, Agnès and Merlin, Jean-Louis and Harlé, Alexandre},\n\tmonth = may,\n\tyear = {2019},\n\tkeywords = {BRAF, FFPE, Genomics, HotSpot, RAS, SOPHiA DDM, Solid Tumor},\n\tpages = {1--8},\n}\n\n

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\n \n\n \n \n \n \n \n \n Profiling of circulating tumor DNA in plasma of non-small cell lung cancer patients, monitoring of epidermal growth factor receptor p.T790M mutated allelic fraction using beads, emulsion, amplification, and magnetics companion assay and evaluation in future application in mimicking circulating tumor cells.\n \n \n \n \n\n\n \n Garcia, J.; Wozny, A.; Geiguer, F.; Delherme, A.; Barthelemy, D.; Merle, P.; Tissot, C.; Jones, F. S.; Johnson, C.; Xing, X.; Xu, Z.; Edelstein, D. L.; Brevet, M.; Souquet, P.; Rodriguez‐Lafrasse, C.; Payen, L.; and Couraud, S.\n\n\n \n\n\n\n Cancer Medicine, 8(8): 3685–3697. May 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Profiling$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{garcia_profiling_2019,\n\ttitle = {Profiling of circulating tumor {DNA} in plasma of non-small cell lung cancer patients, monitoring of epidermal growth factor receptor p.{T790M} mutated allelic fraction using beads, emulsion, amplification, and magnetics companion assay and evaluation in future application in mimicking circulating tumor cells},\n\tvolume = {8},\n\tcopyright = {© 2019 The Authors. Cancer Medicine published by John Wiley \\& Sons Ltd.},\n\tissn = {2045-7634},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/cam4.2244},\n\tdoi = {10.1002/cam4.2244},\n\tabstract = {Cell-free plasma DNA (cfDNA) and mimicking circulating tumor cells (mCTCs) have demonstrated tremendous potential for molecular diagnosis of cancer and have been rapidly implemented in specific settings. However, widespread clinical adoption still faces some obstacles. The purpose was to compare the performance of a BEAMing (beads, emulsion, amplification, and magnetics) assay (OncoBEAM™-epidermal growth factor receptor [EGFR] [Sysmex Inostics]) and a next-generation sequencing assay (NGS; 56G Oncology panel kit, Swift Bioscience) to detect the p.T790M EGFR mutation in cfDNA of non-small cell lung cancer (NSCLC) patients. CfDNA samples (n = 183) were collected within our hospital from patients having a known EGFR sensitizing mutation, and presenting disease progression while under first-line therapy. EGFR mutations were detected using NGS in 42.1\\% of samples during progression in cfDNA. Testing using the OncoBEAM™-EGFR assay enabled detection of the p.T790M EGFR mutation in 40/183 NSCLC patients (21.8\\%) versus 20/183 (10.9\\%), using the NGS assay. Samples that were only positive with the OncoBEAM™-EGFR assay had lower mutant allelic fractions (Mean = 0.1304\\%; SD ± 0.1463\\%). In addition, we investigated the detection of p.T790M in mCTCs using H1975 cells. These cells spiked into whole blood were enriched using the ClearCellFX1 microfluidic device. Using the OncoBEAM™-EGFR assay, p.T790M was detected in as few as 1.33 tumoral cells/mL. Overall, these findings highlight the value of using the OncoBEAM™-EGFR to optimize detection of the p.T790M mutation, as well as the complementary clinical value that each of the mutation detection assay offers: NGS enabled the detection of mutations in other oncogenes that may be relevant to secondary resistance mechanisms, whereas the OncoBEAM™-EGFR assay achieved higher sensitivity for detection of clinically actionable mutations.},\n\tlanguage = {en},\n\tnumber = {8},\n\turldate = {2020-02-11},\n\tjournal = {Cancer Medicine},\n\tauthor = {Garcia, Jessica and Wozny, Anne-Sophie and Geiguer, Florence and Delherme, Aurélia and Barthelemy, David and Merle, Patrick and Tissot, Claire and Jones, Frederick S. and Johnson, Chassidy and Xing, Xiaobin and Xu, Zhenyu and Edelstein, Daniel L. and Brevet, Marie and Souquet, Pierre-Jean and Rodriguez‐Lafrasse, Claire and Payen, Léa and Couraud, Sébastien},\n\tmonth = may,\n\tyear = {2019},\n\tkeywords = {Blood, EGFR, Genomics, Liquid Biopsy, Liquid tumor, NSCLC, SOPHiA DDM, Solid Tumor, cfDNA},\n\tpages = {3685--3697},\n}\n\n

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\n \n\n \n \n \n \n \n \n Significant Impact of the Molecular Profile on the Prognosis of Patients with Myeloproliferative Neoplasms and Splanchnic Vein Thromboses.\n \n \n \n \n\n\n \n Debureaux, P.; Cassinat, B.; Soret-Dulphy, J.; Verger, E.; Maslah, N.; Rautou, P.; Plessier, A.; Valla, D.; Giraudier, S.; and Kiladjian, J.\n\n\n \n\n\n\n Blood, 134(Supplement_1): 836–836. November 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Significant$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{debureaux_significant_2019,\n\ttitle = {Significant {Impact} of the {Molecular} {Profile} on the {Prognosis} of {Patients} with {Myeloproliferative} {Neoplasms} and {Splanchnic} {Vein} {Thromboses}},\n\tvolume = {134},\n\tissn = {0006-4971},\n\turl = {https://ashpublications.org/blood/article/134/Supplement_1/836/427068/Significant-Impact-of-the-Molecular-Profile-on-the},\n\tdoi = {10.1182/blood-2019-123775},\n\tlanguage = {en},\n\tnumber = {Supplement\\_1},\n\turldate = {2020-02-11},\n\tjournal = {Blood},\n\tauthor = {Debureaux, Pierre-Edouard and Cassinat, Bruno and Soret-Dulphy, Juliette and Verger, Emmanuelle and Maslah, Nabih and Rautou, Pierre-Emmanuel and Plessier, Aurelie and Valla, Dominique and Giraudier, Stephane and Kiladjian, Jean-Jacques},\n\tmonth = nov,\n\tyear = {2019},\n\tkeywords = {Abstract, Custom, Custom Panel, Genomics, JAK2V617F, MPN, MYS, Myeloproliferative Neoplasms, SOPHiA DDM},\n\tpages = {836--836},\n}\n\n

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\n \n\n \n \n \n \n \n \n PF220 COMPARISON OF FOUR NGS PANELS AND ANALYSIS OF THEIR CLINICAL UTILITY IN MYELOID HEMATOLOGICAL MALIGNANCIES OF THE MYELOID LINAGE.\n \n \n \n \n\n\n \n Aguilera-Diaz, A.; Vazquez, I.; Ariceta, B.; Mañú, A.; Blasco-Iturri, Z.; Palomino-Echeverria, S.; Larrayoz, M. J.; García-Sanz, R.; Prieto-Conde, M. I.; Chillón, M. C.; Alfonso-Pierola, A.; Rifón-Roca, J.; Prosper, F.; Fernandez-Mercado, M.; and Calasanz, M. J.\n\n\n \n\n\n\n HemaSphere, 3(S1): 62. June 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"PF220$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{aguilera-diaz_pf220_2019,\n\ttitle = {{PF220} {COMPARISON} {OF} {FOUR} {NGS} {PANELS} {AND} {ANALYSIS} {OF} {THEIR} {CLINICAL} {UTILITY} {IN} {MYELOID} {HEMATOLOGICAL} {MALIGNANCIES} {OF} {THE} {MYELOID} {LINAGE}},\n\tvolume = {3},\n\tissn = {2572-9241},\n\turl = {https://journals.lww.com/hemasphere/Fulltext/2019/06001/COMPARISON_OF_FOUR_NGS_PANELS_AND_ANALYSIS_OF.120.aspx},\n\tdoi = {10.1097/01.HS9.0000559096.53543.ef},\n\tabstract = {Background: The diagnosis of myeloid neoplasms (MN) has significantly evolved through the last few decades. Nowadays, blood cell morphology, blasts count, cytogenetics and molecular testing are crucial for MN diagnosis, prognosis and therapy. The advent of personalized medicine has drastically influenced the way we currently diagnose and monitor MN, mainly thanks to Next Generation Sequencing (NGS), which is gradually becoming an essential tool to help clinicians with disease management. To this end, most specialized genetic laboratories have implemented NGS panels targeting a number of different genes relevant to MN.\n        Aims: The aim of the present study is to evaluate the performance of four different targeted NGS gene panels based on their technical features and clinical utility.\n        Methods: A total of 32 patient bone marrow samples were accrued: 17 acute myeloid leukemia (AML), 7 myeloproliferative neoplasms (MPN), 6 myelodysplastic syndromes (MDS), 2 chronic myelomonocytic leukemia (CMML). All of them had been tested with conventional molecular testing and harboured a variety of sequence variants, including single nucleotide variants (SNVs), insertions and deletions (indels). These samples were tested with four NGS panels, three were commercially available panels and one custom. The samples were tested as follows: 17 with Trusight Myeloid Panel (TSMP, 54 genes, amplicon based, Illumina), 16 with SureSeq (23 genes, capture-based, Oxford Gene Technology), 15 with Myeloid Solutions (MYS, 30 genes, capture-based, SOPHiA GENETICS), and all 32 with our custom Pan-Myeloid Panel (PMP, 48 genes, capture-based, SOPHiA GENETICS). Libraries were built following manufacturer's instructions and pair-end sequenced on a Miseq sequencer (Illumina). Analysis of the sequencing data was carried out with a valid performance at the clinical variant allele frequency (VAF) cut-off of 5\\%. Variants were classified by two geneticists with expertise in hematological malignancies; variants classified as “pathogenic” or “likely pathogenic” were kept as clinically relevant.\n        Results: The average sequencing depth was over 5000X in PMP, MYS and TSMP; and over 1600X in SureSeq panel. Nineteen genes are included in all four panels (core myeloid gene set), being ASXL1, CALR, CEBPA, DNMT3A, ETV6, FLT3, IDH1, IDH2, JAK2, KIT, KRAS, MPL, NPM1, NRAS, RUNX1, TET2, TP53, U2AF1 and WT1. A total of 50 clinically relevant variants were detected by all four panels, and 37 of these fell in one gene of the core myeloid gene set. There are 11 discordant variants between panels, 3 in the core myeloid gene set missed only by SureSeq panel (2 FLT3-internal tandem duplications (ITD) and one CALR mutation); and 8 mutations only called by the panels that include those genes in their design (Table 1). Of note, 2 additional FLT3-ITD mutations of 36 bp of length that had been detected by conventional molecular analysis were not called by any of the NGS panels.\n        Summary/Conclusion: After testing the four panels, our data show that there is a high risk of finding different mutations depending on the panel of choice, due both to the panel design and the data analysis method. Based on our data, ITD calling remains a challenge for NGS. This is a major issue, since AML management strongly depends on FLT3-ITD detection. In addition, NGS testing times are hard to harmonise with turnaround time stablished in current European Leukemia Net guidelines. Therefore, conventional molecular testing might need to be kept in place for the correct diagnosis of MN for now.},\n\tlanguage = {en-US},\n\tnumber = {S1},\n\turldate = {2020-02-11},\n\tjournal = {HemaSphere},\n\tauthor = {Aguilera-Diaz, A. and Vazquez, I. and Ariceta, B. and Mañú, A. and Blasco-Iturri, Z. and Palomino-Echeverria, S. and Larrayoz, M. J. and García-Sanz, R. and Prieto-Conde, M. I. and Chillón, M. C. and Alfonso-Pierola, A. and Rifón-Roca, J. and Prosper, F. and Fernandez-Mercado, M. and Calasanz, M. J.},\n\tmonth = jun,\n\tyear = {2019},\n\tkeywords = {Bone Marrow, Genomics, Liquid tumor, MYS, PanMyeloid, Poster},\n\tpages = {62},\n}\n\n

\n\n\n

\n Background: The diagnosis of myeloid neoplasms (MN) has significantly evolved through the last few decades. Nowadays, blood cell morphology, blasts count, cytogenetics and molecular testing are crucial for MN diagnosis, prognosis and therapy. The advent of personalized medicine has drastically influenced the way we currently diagnose and monitor MN, mainly thanks to Next Generation Sequencing (NGS), which is gradually becoming an essential tool to help clinicians with disease management. To this end, most specialized genetic laboratories have implemented NGS panels targeting a number of different genes relevant to MN. Aims: The aim of the present study is to evaluate the performance of four different targeted NGS gene panels based on their technical features and clinical utility. Methods: A total of 32 patient bone marrow samples were accrued: 17 acute myeloid leukemia (AML), 7 myeloproliferative neoplasms (MPN), 6 myelodysplastic syndromes (MDS), 2 chronic myelomonocytic leukemia (CMML). All of them had been tested with conventional molecular testing and harboured a variety of sequence variants, including single nucleotide variants (SNVs), insertions and deletions (indels). These samples were tested with four NGS panels, three were commercially available panels and one custom. The samples were tested as follows: 17 with Trusight Myeloid Panel (TSMP, 54 genes, amplicon based, Illumina), 16 with SureSeq (23 genes, capture-based, Oxford Gene Technology), 15 with Myeloid Solutions (MYS, 30 genes, capture-based, SOPHiA GENETICS), and all 32 with our custom Pan-Myeloid Panel (PMP, 48 genes, capture-based, SOPHiA GENETICS). Libraries were built following manufacturer's instructions and pair-end sequenced on a Miseq sequencer (Illumina). Analysis of the sequencing data was carried out with a valid performance at the clinical variant allele frequency (VAF) cut-off of 5%. Variants were classified by two geneticists with expertise in hematological malignancies; variants classified as “pathogenic” or “likely pathogenic” were kept as clinically relevant. Results: The average sequencing depth was over 5000X in PMP, MYS and TSMP; and over 1600X in SureSeq panel. Nineteen genes are included in all four panels (core myeloid gene set), being ASXL1, CALR, CEBPA, DNMT3A, ETV6, FLT3, IDH1, IDH2, JAK2, KIT, KRAS, MPL, NPM1, NRAS, RUNX1, TET2, TP53, U2AF1 and WT1. A total of 50 clinically relevant variants were detected by all four panels, and 37 of these fell in one gene of the core myeloid gene set. There are 11 discordant variants between panels, 3 in the core myeloid gene set missed only by SureSeq panel (2 FLT3-internal tandem duplications (ITD) and one CALR mutation); and 8 mutations only called by the panels that include those genes in their design (Table 1). Of note, 2 additional FLT3-ITD mutations of 36 bp of length that had been detected by conventional molecular analysis were not called by any of the NGS panels. Summary/Conclusion: After testing the four panels, our data show that there is a high risk of finding different mutations depending on the panel of choice, due both to the panel design and the data analysis method. Based on our data, ITD calling remains a challenge for NGS. This is a major issue, since AML management strongly depends on FLT3-ITD detection. In addition, NGS testing times are hard to harmonise with turnaround time stablished in current European Leukemia Net guidelines. Therefore, conventional molecular testing might need to be kept in place for the correct diagnosis of MN for now.\n

\n\n\n

\n \n\n \n \n \n \n \n \n PS1008 A NEW NEXT-GENERATION SEQUENCING STRATEGY FOR THE SIMULTANEOUS DETECTION OF GENE MUTATIONS AND COPY NUMBER VARIATIONS IN MYELOID MALIGNANCIES.\n \n \n \n \n\n\n \n Prieto-Conde, M. I.; Vázquez, I.; Fernández-Mercado, M.; Gutiérrez, N. C.; González-Martínez, T.; Larrayoz, M. J.; Sarasquete, M. E.; Alcoceba, M.; González-Calle, V.; González-Díaz, M.; García-Sanz, R.; Calasanz, M. J.; and Chillón, M. C.\n\n\n \n\n\n\n HemaSphere, 3(S1): 453. June 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"PS1008$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{prieto-conde_ps1008_2019,\n\ttitle = {{PS1008} {A} {NEW} {NEXT}-{GENERATION} {SEQUENCING} {STRATEGY} {FOR} {THE} {SIMULTANEOUS} {DETECTION} {OF} {GENE} {MUTATIONS} {AND} {COPY} {NUMBER} {VARIATIONS} {IN} {MYELOID} {MALIGNANCIES}},\n\tvolume = {3},\n\tissn = {2572-9241},\n\turl = {https://journals.lww.com/hemasphere/Abstract/2019/06001/PS1008_A_NEW_NEXT_GENERATION_SEQUENCING_STRATEGY.898.aspx},\n\tdoi = {10.1097/01.HS9.0000562328.88850.42},\n\tabstract = {Background: The diagnosis of myeloid malignances includes multiple testing strategies for genetic abnormalities assessment, including gene mutations and copy number variations (CNVs), which is critical for therapeutic decision making. Although next-generation sequencing (NGS) has been implemented in clinical diagnostic laboratories, it has focused on the detection of single nucleotide variants and small indels, while CNV detection still relies on karyotyping and fluorescence in situ hybridization (FISH).\n        Aims: In the present study, a new strategy was developed and validated to simultaneously detect CNVs and somatic mutations in a series of patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) by using a capture-based NGS custom panel.\n        Methods: We designed a NGS target-DNA panel associated to a custom bioinformatic pipeline (Sophia Genetics) for one-step identification of somatic and germline mutations in 48 genes, as well as CNV. The CNV algorithm was based on the coverage levels across samples within the same batch. We studied the complete CDS or targeted exons of 16 genes sited in chromosome regions 5q14-q35 (5 genes), 7q22-q36 (3 genes), 8q12-q24 (4 genes), 20q11-q13 (3 genes), 17p13 (1 gene, TP53), as well as other genes in 5p, 7p, 20p and 17q as control regions. We analyzed 45 diagnostic samples of myeloid malignances (39 AML and 6 MDS), that had previously been characterized by FISH and/or karyotyping, as well as by conventional molecular techniques (FLT3-ITD, NPM1 and CEBPA mutations). Paired-end sequencing runs were performed on a MiSeq (Illumina) genome sequencer.\n        Results: We detected 133 pathogenic mutations in 42 patients, including all 8 FLT3-ITD (size 18–204 bp) and 4 mutations in CEBPA. We were also able to detect exon-level duplications, such as KMT2A (MLL) partial tandem duplication, in 3 cases. Four different CNV types were distinguished by the algorithm: del(5q), del(7q), del(20q) and trisomy 8, showing a full concordance with those alterations identified by FISH probes. All 8 patients with 5q33 deletions (8/8, 100\\%) were detected by NGS, as well as 5 cases with 7q35 deletion (5/5, 100\\%), 3 patients with trisomy 8 (3/3, 100\\%) and 3 with 20q12 deletion (3/3, 100\\%). None of the patients presented 17p abnormalities by any technique. Moreover, we detected alterations in the copy number of KMT2A gene in 4 of 5 patients with 11q23 alterations (translocation or amplification) identified by FISH and cytogenetics. One case of t(11;19)(q23;p13) was not detected by NGS, which is explained because the breakpoint region of this translocation was not covered by our design. Next panel will overcome this caveat by including the complete CDS of the KMT2A gene. Finally, NGS estimated abnormal copy numbers in three cases of 7q deletions and one trisomy 8, where FISH and cytogenetics had failed to detect any change.\n        Summary/Conclusion: Our study demonstrates that both somatic mutations and targeted CNVs can be accurately detected by NGS covering adequate exons on selected genes. Therefore, this strategy complements conventional methods to identify biomarkers for the diagnosis, prognosis and therapy of myeloid malignances.},\n\tlanguage = {en-US},\n\tnumber = {S1},\n\turldate = {2020-02-11},\n\tjournal = {HemaSphere},\n\tauthor = {Prieto-Conde, M. I. and Vázquez, I. and Fernández-Mercado, M. and Gutiérrez, N. C. and González-Martínez, T. and Larrayoz, M. J. and Sarasquete, M. E. and Alcoceba, M. and González-Calle, V. and González-Díaz, M. and García-Sanz, R. and Calasanz, M. J. and Chillón, M. C.},\n\tmonth = jun,\n\tyear = {2019},\n\tkeywords = {AML, Abstract, CNV, Custom, Genomics, INDEL, Liquid tumor, MDS, SNV},\n\tpages = {453},\n}\n\n

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\n Background: The diagnosis of myeloid malignances includes multiple testing strategies for genetic abnormalities assessment, including gene mutations and copy number variations (CNVs), which is critical for therapeutic decision making. Although next-generation sequencing (NGS) has been implemented in clinical diagnostic laboratories, it has focused on the detection of single nucleotide variants and small indels, while CNV detection still relies on karyotyping and fluorescence in situ hybridization (FISH). Aims: In the present study, a new strategy was developed and validated to simultaneously detect CNVs and somatic mutations in a series of patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) by using a capture-based NGS custom panel. Methods: We designed a NGS target-DNA panel associated to a custom bioinformatic pipeline (Sophia Genetics) for one-step identification of somatic and germline mutations in 48 genes, as well as CNV. The CNV algorithm was based on the coverage levels across samples within the same batch. We studied the complete CDS or targeted exons of 16 genes sited in chromosome regions 5q14-q35 (5 genes), 7q22-q36 (3 genes), 8q12-q24 (4 genes), 20q11-q13 (3 genes), 17p13 (1 gene, TP53), as well as other genes in 5p, 7p, 20p and 17q as control regions. We analyzed 45 diagnostic samples of myeloid malignances (39 AML and 6 MDS), that had previously been characterized by FISH and/or karyotyping, as well as by conventional molecular techniques (FLT3-ITD, NPM1 and CEBPA mutations). Paired-end sequencing runs were performed on a MiSeq (Illumina) genome sequencer. Results: We detected 133 pathogenic mutations in 42 patients, including all 8 FLT3-ITD (size 18–204 bp) and 4 mutations in CEBPA. We were also able to detect exon-level duplications, such as KMT2A (MLL) partial tandem duplication, in 3 cases. Four different CNV types were distinguished by the algorithm: del(5q), del(7q), del(20q) and trisomy 8, showing a full concordance with those alterations identified by FISH probes. All 8 patients with 5q33 deletions (8/8, 100%) were detected by NGS, as well as 5 cases with 7q35 deletion (5/5, 100%), 3 patients with trisomy 8 (3/3, 100%) and 3 with 20q12 deletion (3/3, 100%). None of the patients presented 17p abnormalities by any technique. Moreover, we detected alterations in the copy number of KMT2A gene in 4 of 5 patients with 11q23 alterations (translocation or amplification) identified by FISH and cytogenetics. One case of t(11;19)(q23;p13) was not detected by NGS, which is explained because the breakpoint region of this translocation was not covered by our design. Next panel will overcome this caveat by including the complete CDS of the KMT2A gene. Finally, NGS estimated abnormal copy numbers in three cases of 7q deletions and one trisomy 8, where FISH and cytogenetics had failed to detect any change. Summary/Conclusion: Our study demonstrates that both somatic mutations and targeted CNVs can be accurately detected by NGS covering adequate exons on selected genes. Therefore, this strategy complements conventional methods to identify biomarkers for the diagnosis, prognosis and therapy of myeloid malignances.\n

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\n \n\n \n \n \n \n \n \n Can somatic BRCA2 status solve a case of olaparib monotherapy resistance?.\n \n \n \n \n\n\n \n Pietragalla, A.; Minucci, A.; Marchetti, C.; Scambia, G.; and Fagotti, A.\n\n\n \n\n\n\n International Journal of Gynecologic Cancer, 29(9): 1440–1445. November 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Can$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{pietragalla_can_2019,\n\ttitle = {Can somatic {BRCA2} status solve a case of olaparib monotherapy resistance?},\n\tvolume = {29},\n\tcopyright = {© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.},\n\tissn = {1048-891X, 1525-1438},\n\turl = {https://ijgc.bmj.com/content/29/9/1440},\n\tdoi = {10.1136/ijgc-2019-000757},\n\tabstract = {A Caucasian 55-year-old woman with FIGO stage IC high-grade serous ovarian cancer underwent total hysterectomy, bilateral salpingo-oophorectomy, infracolic omentectomy, and bilateral pelvic and para-aortic lymphadenectomy in November 2013. Subsequently, she received six cycles of paclitaxel (175},\n\tlanguage = {en},\n\tnumber = {9},\n\turldate = {2020-02-11},\n\tjournal = {International Journal of Gynecologic Cancer},\n\tauthor = {Pietragalla, Antonella and Minucci, Angelo and Marchetti, Claudia and Scambia, Giovanni and Fagotti, Anna},\n\tmonth = nov,\n\tyear = {2019},\n\tpmid = {31537621},\n\tkeywords = {BRCA2, Blood, Clinical study, Commercial, FFPE, Fresh-Frozen, Genomics, HCS, Hereditary Disorders, Olaparib, Oncology, SOPHiA DDM, Solid Tumor, Targeted},\n\tpages = {1440--1445},\n}\n\n

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\n \n\n \n \n \n \n \n \n Peritoneal washing is an adequate source for somatic BRCA1/2 mutation testing in ovarian malignancies.\n \n \n \n \n\n\n \n Barquín, M.; Maximiano, C.; Pérez-Barrios, C.; Sanchez-Herrero, E.; Soriano, M.; Colmena, M.; García-Espantaleón, M.; Tejerina González, E.; Gutierrez, L.; Sánchez Ruiz, A. C.; Torrente, M.; Provencio, M.; and Romero, A.\n\n\n \n\n\n\n Pathology - Research and Practice, 215(2): 392–394. February 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Peritoneal$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{barquin_peritoneal_2019,\n\ttitle = {Peritoneal washing is an adequate source for somatic {BRCA1}/2 mutation testing in ovarian malignancies},\n\tvolume = {215},\n\tissn = {0344-0338},\n\turl = {http://www.sciencedirect.com/science/article/pii/S034403381830894X},\n\tdoi = {10.1016/j.prp.2018.10.028},\n\tabstract = {Genetic screening for BRCA mutations should be offered to all women diagnosed with epithelial ovarian, fallopian tube, and/or peritoneal cancers given the implications for treatment options and cancer risk assessments. Yet, while germline breast cancer susceptibility gene 1 (BRCA1) and breast cancer susceptibility gene 2 (BRCA2) testing is commonly performed, BRCA1/2 somatic mutations testing is rather challenging since the poor quality of DNA extracted from formalin fixed paraffin embedded (FFPE) samples can significantly impair this process. Peritoneal lavage is routinely performed in surgeries of suspected ovarian malignancies. We have analyzed fresh tumor, peritoneal lavage and blood samples from ten patients and we have found an excellent agreement (88\\%) between fresh tumor and peritoneal lavage for BRCA mutation testing. Importantly, 112 of the 114 genomic alterations detected in fresh tumor samples were also found in peritoneal lavage fluids. Our data suggest that peritoneal washings can indeed streamline BRCA genes mutation testing procedures.},\n\tlanguage = {en},\n\tnumber = {2},\n\turldate = {2020-02-11},\n\tjournal = {Pathology - Research and Practice},\n\tauthor = {Barquín, Miguel and Maximiano, Constanza and Pérez-Barrios, Clara and Sanchez-Herrero, Estela and Soriano, María and Colmena, Marta and García-Espantaleón, Manuel and Tejerina González, Eva and Gutierrez, Lourdes and Sánchez Ruiz, Antonio Carlos and Torrente, María and Provencio, Mariano and Romero, Atocha},\n\tmonth = feb,\n\tyear = {2019},\n\tkeywords = {BRCA1, BRCA1/2, BRCA2, Blood, Bundle, FFPE, Fresh-Frozen, Genomics, Illumina Sequencer, Oncology, Ovarian Cancer, Peritoneal washing, SOPHiA DDM, Solid Tumor},\n\tpages = {392--394},\n}\n\n

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\n \n\n \n \n \n \n \n \n TRPM4 mutations to cause autosomal recessive and not autosomal dominant Brugada type 1 syndrome.\n \n \n \n \n\n\n \n Janin, A.; Bessière, F.; Georgescu, T.; Chanavat, V.; Chevalier, P.; and Millat, G.\n\n\n \n\n\n\n European Journal of Medical Genetics, 62(6): 103527. June 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"TRPM4$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{janin_trpm4_2019,\n\ttitle = {{TRPM4} mutations to cause autosomal recessive and not autosomal dominant {Brugada} type 1 syndrome},\n\tvolume = {62},\n\tissn = {1769-7212},\n\turl = {http://www.sciencedirect.com/science/article/pii/S1769721218302179},\n\tdoi = {10.1016/j.ejmg.2018.08.008},\n\tabstract = {Cardiac channelopathies, mainly Long QT and Brugada syndromes, are genetic disorders for which genotype/phenotypes relationships remains to be improved. To provide new insights into the Brugada syndrome pathophysiology, a mutational study was performed on a 64-year-old man presented with isolated exertional dyspnea (NYHA class: II-III), hypertension, chronic kidney disease, coronary disease, an electrocardiogram suggesting a Brugada type 1-like pattern with ST-segment elevation in leads V1-V2. Molecular diagnosis study was performed using molecular strategy based on the sequencing of a panel of 19 Brugada-associated genes. The proband was carrier of 2 TRPM4 null alleles [IVS9+1G {\\textgreater} A and p. Trp525X] resulting in the absence of functional hTRPM4 proteins. Due to this unexpected genotype, meta-analysis of previously reported TRPM4 variations associated with cardiac pathologies was performed using ACMG guidelines. All were detected in a heterozygous status. This additional meta-analysis indicated that most of them could not be considered definitely as pathogen. In conclusion, our study reports, for the first time, identification of compound heterozygous TRPM4 null mutations in a proband with, at an arrhythmogenic level, only a Brugada type 1-like electrocardiogram. By combining the genotype/phenotype relationship of this case and analysis of previously reported TRPM4 variations, we suggest that loss-of-function TRPM4 variations, in a heterozygous status, could not be considered as pathogenic or likely pathogenic mutations in cardiac channelopathies such as Long QT syndrome or Brugada syndrome.},\n\tlanguage = {en},\n\tnumber = {6},\n\turldate = {2020-02-11},\n\tjournal = {European Journal of Medical Genetics},\n\tauthor = {Janin, Alexandre and Bessière, Francis and Georgescu, Tudor and Chanavat, Valérie and Chevalier, Philippe and Millat, Gilles},\n\tmonth = jun,\n\tyear = {2019},\n\tkeywords = {Brugada syndrome, Bundle, Cardiology, Custom Pipeline, Genomics, Hereditary Disorders, INDEL, Illumina Sequencer, SNV, SOPHiA DDM, Targeted},\n\tpages = {103527},\n}\n\n

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\n \n\n \n \n \n \n \n \n Novel BRCA1 Large Genomic Rearrangements in Italian Breast/Ovarian Cancer Patients.\n \n \n \n \n\n\n \n Rizza, R.; Hackmann, K.; Paris, I.; Minucci, A.; De Leo, R.; Schrock, E.; Urbani, A.; Capoluongo, E.; Gelli, G.; and Concolino, P.\n\n\n \n\n\n\n Molecular Diagnosis & Therapy, 23(1): 121–126. February 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Novel$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{rizza_novel_2019,\n\ttitle = {Novel {BRCA1} {Large} {Genomic} {Rearrangements} in {Italian} {Breast}/{Ovarian} {Cancer} {Patients}},\n\tvolume = {23},\n\tissn = {1179-2000},\n\turl = {https://doi.org/10.1007/s40291-018-0376-2},\n\tdoi = {10.1007/s40291-018-0376-2},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2020-02-11},\n\tjournal = {Molecular Diagnosis \\& Therapy},\n\tauthor = {Rizza, Roberta and Hackmann, Karl and Paris, Ida and Minucci, Angelo and De Leo, Rossella and Schrock, Evelin and Urbani, Andrea and Capoluongo, Ettore and Gelli, Gianfranco and Concolino, Paola},\n\tmonth = feb,\n\tyear = {2019},\n\tkeywords = {Alu, BRCA1, Blood, CNV, Genomics, HBOC, Hereditary Breast and Ovarian Cancer Syndrome, Hereditary Disorders, SOPHiA DDM},\n\tpages = {121--126},\n}\n\n

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\n \n\n \n \n \n \n \n \n Identification of a novel large EPCAM-MSH2 duplication, concurrently with LOHs in chromosome 20 and X, in a family with Lynch syndrome.\n \n \n \n \n\n\n \n Pirini, F.; Tedaldi, G.; Danesi, R.; Cangini, I.; Tumedei, M. M.; Ferrari, A.; Vitali, S.; De Maio, G.; Terragna, C.; Solli, V.; Tebaldi, M.; Puccetti, M.; Zampiga, V.; Ravegnani, M.; Ulivi, P.; Falcini, F.; Martinelli, G.; and Calistri, D.\n\n\n \n\n\n\n International Journal of Colorectal Disease, 34(11): 1999–2002. November 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Identification$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{pirini_identification_2019,\n\ttitle = {Identification of a novel large {EPCAM}-{MSH2} duplication, concurrently with {LOHs} in chromosome 20 and {X}, in a family with {Lynch} syndrome},\n\tvolume = {34},\n\tissn = {1432-1262},\n\turl = {https://doi.org/10.1007/s00384-019-03414-y},\n\tdoi = {10.1007/s00384-019-03414-y},\n\tlanguage = {en},\n\tnumber = {11},\n\turldate = {2020-02-11},\n\tjournal = {International Journal of Colorectal Disease},\n\tauthor = {Pirini, Francesca and Tedaldi, Gianluca and Danesi, Rita and Cangini, Ilaria and Tumedei, Maria Maddalena and Ferrari, Anna and Vitali, Silvia and De Maio, Giulia and Terragna, Carolina and Solli, Vincenza and Tebaldi, Michela and Puccetti, Maurizio and Zampiga, Valentina and Ravegnani, Mila and Ulivi, Paola and Falcini, Fabio and Martinelli, Giovanni and Calistri, Daniele},\n\tmonth = nov,\n\tyear = {2019},\n\tkeywords = {CNV, Case Study, EPCAM, FFPE, Genomics, HCS, Hereditary Disorders, Lynch syndrome, MSH2, Targeted},\n\tpages = {1999--2002},\n}\n\n

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\n \n\n \n \n \n \n \n \n PS1009 INDIVIDUALIZED FOLLOW-UP IN ADULT ACUTE MYELOID LEUKEMIA USING NGS.\n \n \n \n \n\n\n \n Iturri, Z. B.; Vazquez, I.; Ariceta, B.; Echeverria, S. P.; Diaz, A. A.; Marin, A. D. U.; Mañu, A.; Larrayoz, M. J.; Viguria, M. C.; Zudaire, M. T.; Bandres, E.; Mateos, M. D. C.; Fernandez, S. V.; Pierola, A. A.; Roca, J. R.; Prosper, F.; Mercado, M. F.; and Calasanz, M. J.\n\n\n \n\n\n\n HemaSphere, 3(S1): 453–454. June 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"PS1009$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{iturri_ps1009_2019,\n\ttitle = {{PS1009} {INDIVIDUALIZED} {FOLLOW}-{UP} {IN} {ADULT} {ACUTE} {MYELOID} {LEUKEMIA} {USING} {NGS}},\n\tvolume = {3},\n\tissn = {2572-9241},\n\turl = {https://journals.lww.com/hemasphere/Fulltext/2019/06001/INDIVIDUALIZED_FOLLOW_UP_IN_ADULT_ACUTE_MYELOID.899.aspx},\n\tdoi = {10.1097/01.HS9.0000562332.26969.1f},\n\tabstract = {Background: The current standard for morphologic complete remission in acute myeloid leukemia (AML) is less than 5\\% myeloblasts, but mounting data show this criterion is not sufficiently sound. Alternative methods, such as quantitative reverse-transcription polymerase chain reaction (RT-qPCR), are widely used to detect molecular responses, but it relies on the initial detection of a fusion transcript, or overexpressed gene. Deeper knowledge of the clonal dynamics of AML could potentially be of clinical utility. A wide scope testing technology is required in order to address the molecular heterogeneity of AML. We reasoned that an appropriate Next Generation Sequencing (NGS) panel could be a useful tool to provide personalized molecular monitoring in patients diagnosed as or progress to AML.\n        Aims: The aim of this study is to evaluate the clinical utility of NGS panel in the prognostic and treatment monitoring in patients diagnosed as or progress to AML.\n        Methods: We studied the genomic alterations of 19 AML cases (13 de novo, and 6 secondary to a preexisting MN) during disease follow-up; 11 of these patients received hematopoietic stem cell transplantation (HSCT). The 67 samples were tested with our custom Pan-Myeloid Panel (48 genes, SOPHiA GENETICS). Samples were provided by the Biobank of the University of Navarra and were processed following SOP approved by the Ethical and Scientific Committee of the University. Libraries were pair-end sequenced on a Miseq sequencer (Illumina). Sequencing data were analyzed by two geneticists with expertise in hematological malignancies.\n        Results: Sequencing data identified genomic clonal markers with clinical utility (i.e. diagnostic, prognostic, and/or predictive value) in 89,5\\% of cases. In patients not receiving HSCT (n = 8), NGS was useful to classify them in two genetic profiles: those achieving molecular complete remission (mCR) (n = 2) (Figure 1A), and those not responding to treatment and undergoing disease progression (n = 6) (Figure 1B). In the last group, NGS identified pathogenic variants in DDX41, DNMT3A, IDH1, JAK2, NRAS, SRSF2, U2AF1 genes. In patients receiving HSCT (n = 11), NGS also classified patients in two groups: those clearing pathogenic variants upon HSCT (n = 5) (Figure 1C), and those with persisting variants, not achieving mCR (n = 6) (Figure 1D). Again, NGS identified initial clones harboring pathogenic variants, like KRAS, that appeared in the 66\\% of the patients after HSCT failure. Also mutations in CBL, DNMT3A, FLT3, JAK2, KRAS and SRSF2 genes are present in this cohort of patients.\n        In two cases, NGS either did not detect any clinically relevant variant, or it detected variants only after disease progression; in these two cases an NGS panel was insufficient, and therefore more comprehensive studies are needed (e.g. exomes). Of note, NGS data detected clones harboring pathogenic variants in two patients with negative minimal residual disease (MRD), as measured by flow cytometry (Figure 1D), indicating that NGS could complement current gold standard follow-up method in some instances.\n        Summary/Conclusion: A 48-gene panel NGS has been useful for molecular diagnosis, treatment follow-up, and relapse detection in nearly 90\\% of the AML cases included in our study (17 of 19). NGS was also useful for following mutational clearance and/or clonal evolution in 12 of 19 patients (63\\%), including cases undergoing HSCT. According to our data, NGS could be of clinical utility for routine diagnosis and follow-up in an elevated proportion of AML patients, even complementing immunophenotypic techniques for MRD monitoring in some instances.},\n\tlanguage = {en-US},\n\tnumber = {S1},\n\turldate = {2020-02-11},\n\tjournal = {HemaSphere},\n\tauthor = {Iturri, Z. Blasco and Vazquez, I. and Ariceta, B. and Echeverria, S. Palomino and Diaz, A. Aguilera and Marin, A. D. Urribarri and Mañu, A. and Larrayoz, M. J. and Viguria, M. C. and Zudaire, M. T. and Bandres, E. and Mateos, M. D. C. and Fernandez, S. Villar and Pierola, A. Alfonso and Roca, J. Rifon and Prosper, F. and Mercado, M. Fernandez and Calasanz, M. J.},\n\tmonth = jun,\n\tyear = {2019},\n\tkeywords = {AML, Abstract, Custom, Follow-Up, Genomics, Liquid tumor, Targeted},\n\tpages = {453--454},\n}\n\n

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\n Background: The current standard for morphologic complete remission in acute myeloid leukemia (AML) is less than 5% myeloblasts, but mounting data show this criterion is not sufficiently sound. Alternative methods, such as quantitative reverse-transcription polymerase chain reaction (RT-qPCR), are widely used to detect molecular responses, but it relies on the initial detection of a fusion transcript, or overexpressed gene. Deeper knowledge of the clonal dynamics of AML could potentially be of clinical utility. A wide scope testing technology is required in order to address the molecular heterogeneity of AML. We reasoned that an appropriate Next Generation Sequencing (NGS) panel could be a useful tool to provide personalized molecular monitoring in patients diagnosed as or progress to AML. Aims: The aim of this study is to evaluate the clinical utility of NGS panel in the prognostic and treatment monitoring in patients diagnosed as or progress to AML. Methods: We studied the genomic alterations of 19 AML cases (13 de novo, and 6 secondary to a preexisting MN) during disease follow-up; 11 of these patients received hematopoietic stem cell transplantation (HSCT). The 67 samples were tested with our custom Pan-Myeloid Panel (48 genes, SOPHiA GENETICS). Samples were provided by the Biobank of the University of Navarra and were processed following SOP approved by the Ethical and Scientific Committee of the University. Libraries were pair-end sequenced on a Miseq sequencer (Illumina). Sequencing data were analyzed by two geneticists with expertise in hematological malignancies. Results: Sequencing data identified genomic clonal markers with clinical utility (i.e. diagnostic, prognostic, and/or predictive value) in 89,5% of cases. In patients not receiving HSCT (n = 8), NGS was useful to classify them in two genetic profiles: those achieving molecular complete remission (mCR) (n = 2) (Figure 1A), and those not responding to treatment and undergoing disease progression (n = 6) (Figure 1B). In the last group, NGS identified pathogenic variants in DDX41, DNMT3A, IDH1, JAK2, NRAS, SRSF2, U2AF1 genes. In patients receiving HSCT (n = 11), NGS also classified patients in two groups: those clearing pathogenic variants upon HSCT (n = 5) (Figure 1C), and those with persisting variants, not achieving mCR (n = 6) (Figure 1D). Again, NGS identified initial clones harboring pathogenic variants, like KRAS, that appeared in the 66% of the patients after HSCT failure. Also mutations in CBL, DNMT3A, FLT3, JAK2, KRAS and SRSF2 genes are present in this cohort of patients. In two cases, NGS either did not detect any clinically relevant variant, or it detected variants only after disease progression; in these two cases an NGS panel was insufficient, and therefore more comprehensive studies are needed (e.g. exomes). Of note, NGS data detected clones harboring pathogenic variants in two patients with negative minimal residual disease (MRD), as measured by flow cytometry (Figure 1D), indicating that NGS could complement current gold standard follow-up method in some instances. Summary/Conclusion: A 48-gene panel NGS has been useful for molecular diagnosis, treatment follow-up, and relapse detection in nearly 90% of the AML cases included in our study (17 of 19). NGS was also useful for following mutational clearance and/or clonal evolution in 12 of 19 patients (63%), including cases undergoing HSCT. According to our data, NGS could be of clinical utility for routine diagnosis and follow-up in an elevated proportion of AML patients, even complementing immunophenotypic techniques for MRD monitoring in some instances.\n

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\n \n\n \n \n \n \n \n \n A Case of Leukoencephalopathy and Small Vessels Disease Caused by a Novel HTRA1 Homozygous Mutation.\n \n \n \n \n\n\n \n Gündüz, T.; Demirkol, Y.; Doğan, Ö.; Demir, S.; and Akçakaya, N. H.\n\n\n \n\n\n\n Journal of Stroke and Cerebrovascular Diseases, 28(11): 104354. November 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{gunduz_case_2019,\n\ttitle = {A {Case} of {Leukoencephalopathy} and {Small} {Vessels} {Disease} {Caused} by a {Novel} {HTRA1} {Homozygous} {Mutation}},\n\tvolume = {28},\n\tissn = {1052-3057},\n\turl = {http://www.sciencedirect.com/science/article/pii/S1052305719304070},\n\tdoi = {10.1016/j.jstrokecerebrovasdis.2019.104354},\n\tabstract = {Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a heritable, rare small vessel disease, which is caused by HTRA1 mutations and mostly reported Japanese and Chinese population. CARASIL is an orphan disease, which presents with progressive motor and cognitive impairment, alopecia, and spondylosis. The disease typically starts with lumbago at early twenties. Ischemic strokes start at mid-twenties. Patients have no cardiovascular or any other risk factors. Multiple lacunar infarcts and leukoencephalopathy cause progressive neurologic involvement. Leukoencephalopathy and small vessel disease without any risk factors is a significant finding for the differential diagnosis of HTRA1 gene pathology. This report presents clinical and genetic features of a rare case of typical CARASIL from Turkey who was followed with uncertain diagnoses for years.},\n\tlanguage = {en},\n\tnumber = {11},\n\turldate = {2020-02-11},\n\tjournal = {Journal of Stroke and Cerebrovascular Diseases},\n\tauthor = {Gündüz, Tuncay and Demirkol, Yasemin and Doğan, Özlem and Demir, Serkan and Akçakaya, Nihan Hande},\n\tmonth = nov,\n\tyear = {2019},\n\tkeywords = {CES, Commercial, Genomic Hereditary Disorders, HTRA1, Illumina Sequencer, Large panel, Leukoencephalopathy, SOPHiA DDM, Small Vessels Disease},\n\tpages = {104354},\n}\n\n

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\n \n\n \n \n \n \n \n \n PF238 TUMOR NGS-PANEL UTILITY IN THE IDENTIFICATION OF GERMLINE VARIANTS IN MYELOID MALIGNANCIES.\n \n \n \n \n\n\n \n Palomino-Echeverria, S.; Vazquez, I.; Alfonso-Pierola, A.; Ariceta, B.; Blasco-Iturri, Z.; Aguilera-Diaz, A.; Larrayoz, M. J.; Mañu, A.; Bernal del Castillo, T.; Olivares Salaverri, M.; Olave Rubio, M.; Rifon-Roca, J.; Prosper, F.; Fernandez-Mercado, M.; and Calasanz, M. J.\n\n\n \n\n\n\n HemaSphere, 3(S1): 71–72. June 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"PF238$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{palomino-echeverria_pf238_2019,\n\ttitle = {{PF238} {TUMOR} {NGS}-{PANEL} {UTILITY} {IN} {THE} {IDENTIFICATION} {OF} {GERMLINE} {VARIANTS} {IN} {MYELOID} {MALIGNANCIES}},\n\tvolume = {3},\n\tissn = {2572-9241},\n\turl = {https://journals.lww.com/hemasphere/Fulltext/2019/06001/TUMOR_NGS_PANEL_UTILITY_IN_THE_IDENTIFICATION_OF.138.aspx},\n\tdoi = {10.1097/01.HS9.0000559168.09663.8e},\n\tabstract = {Background: Myeloid neoplasms (MN) are heterogeneous clonal diseases arising in hematopoietic cells. Although MN are usually sporadic late-onset cancers, growing evidence suggests that an important number of cases could emerge as a consequence of inherited predisposition. Since many of the genes associated with hereditary myeloid malignancies (HMM) are also affected by somatic mutations in sporadic MN, there is a chance of identifying variants of germline nature when performing Next Generation Sequencing (NGS) tumor testing. Given the clinical relevance of the issue, it is important to correctly classify those suspicious variants as somatic or germline.\n        Aims: We intended to identify hematological patients with potentially inherited variants in a myeloid cohort with tumor-only NGS data.\n        Methods: We reviewed 332 NGS clinical reports of samples from 299 myeloid patients tested with tumor-only sequencing during 2018 in our lab. We considered variants detected in BM sample at a 40–60\\% VAF classified as pathogenic, likely pathogenic or of uncertain significance variants as potentially inherited.\n        On the one hand, for patients with available follow-up data, we considered as suggestive of inherited origin variants with stable VAF. On the other hand, for patients with available non-myeloid tissue we sequenced 20 samples including DNA derived from cultured skin fibroblasts (n = 3), cultured bone marrow (BM) fibroblasts (n = 1), hair follicles (n = 5), purified CD3+ T cells (n = 6) and buccal swab (n = 5). Libraries were sequenced using our custom Pan-Myeloid Panel, which includes 22 genes related to HMM (PMP, 48 genes, capture-based, SOPHiA GENETICS). All patients signed a written informed consent form for genetic testing, research and tissue banking (Biobank of the University of Navarra). Samples were processed following Standard Operating Procedures approved by the Ethical and Scientific Committee of the University.\n        Results: In total, 130 suspicious variants in HMM-related genes were identified in tumor sample from 100 patients. Follow-up data was available for 8 patients harboring a total of 9 variants. Six variants from 5 patients presented stable VAFs and clearance of accompanying variants during follow-up; this might be due to an inherited event, although germline tissue testing is required for confirmation. Suspicious germline variants were found in ASXL1, DDX41, RUNX1 and IKZF1. Additionally, non-myeloid tissue was available for 7 patients harboring a total of 8 variants. All 8 (100\\%) variants were confirmed of inherited origin. Germline variants were detected in ASXL1, DDX41, SH2B3, TET2 and NF1 (Figure 1).\n        Summary/Conclusion: This study shows that NGS panels may incidentally detect inherited variants related to predisposition to MN despite not having been designed for that purpose. Our data supports the importance of considering variants incidentally found upon tumor-only sequencing as potentially of germline origin. Indeed, one third of our cohort was suspicious of carrying a germline variant. We could confirm as inherited 100\\% of tested variants from patients with non-myeloid tissue available. For patients with follow-up data, VAF may help in discriminating ambiguous variants, but ultimately germline tissue sequencing is needed to determine the nature of the variant.\n        These findings suggest that there is an increasing need for germline tissue testing along with the appropriate genetic counseling associated to it.},\n\tlanguage = {en-US},\n\tnumber = {S1},\n\turldate = {2020-02-11},\n\tjournal = {HemaSphere},\n\tauthor = {Palomino-Echeverria, S. and Vazquez, I. and Alfonso-Pierola, A. and Ariceta, B. and Blasco-Iturri, Z. and Aguilera-Diaz, A. and Larrayoz, M. J. and Mañu, A. and Bernal del Castillo, T. and Olivares Salaverri, M. and Olave Rubio, M. and Rifon-Roca, J. and Prosper, F. and Fernandez-Mercado, M. and Calasanz, M. J.},\n\tmonth = jun,\n\tyear = {2019},\n\tkeywords = {Custom Pan-Myeloid Panel, Genomics, Hereditary Disorders, Inherited Variants, Liquid tumor, Poster},\n\tpages = {71--72},\n}\n\n

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\n Background: Myeloid neoplasms (MN) are heterogeneous clonal diseases arising in hematopoietic cells. Although MN are usually sporadic late-onset cancers, growing evidence suggests that an important number of cases could emerge as a consequence of inherited predisposition. Since many of the genes associated with hereditary myeloid malignancies (HMM) are also affected by somatic mutations in sporadic MN, there is a chance of identifying variants of germline nature when performing Next Generation Sequencing (NGS) tumor testing. Given the clinical relevance of the issue, it is important to correctly classify those suspicious variants as somatic or germline. Aims: We intended to identify hematological patients with potentially inherited variants in a myeloid cohort with tumor-only NGS data. Methods: We reviewed 332 NGS clinical reports of samples from 299 myeloid patients tested with tumor-only sequencing during 2018 in our lab. We considered variants detected in BM sample at a 40–60% VAF classified as pathogenic, likely pathogenic or of uncertain significance variants as potentially inherited. On the one hand, for patients with available follow-up data, we considered as suggestive of inherited origin variants with stable VAF. On the other hand, for patients with available non-myeloid tissue we sequenced 20 samples including DNA derived from cultured skin fibroblasts (n = 3), cultured bone marrow (BM) fibroblasts (n = 1), hair follicles (n = 5), purified CD3+ T cells (n = 6) and buccal swab (n = 5). Libraries were sequenced using our custom Pan-Myeloid Panel, which includes 22 genes related to HMM (PMP, 48 genes, capture-based, SOPHiA GENETICS). All patients signed a written informed consent form for genetic testing, research and tissue banking (Biobank of the University of Navarra). Samples were processed following Standard Operating Procedures approved by the Ethical and Scientific Committee of the University. Results: In total, 130 suspicious variants in HMM-related genes were identified in tumor sample from 100 patients. Follow-up data was available for 8 patients harboring a total of 9 variants. Six variants from 5 patients presented stable VAFs and clearance of accompanying variants during follow-up; this might be due to an inherited event, although germline tissue testing is required for confirmation. Suspicious germline variants were found in ASXL1, DDX41, RUNX1 and IKZF1. Additionally, non-myeloid tissue was available for 7 patients harboring a total of 8 variants. All 8 (100%) variants were confirmed of inherited origin. Germline variants were detected in ASXL1, DDX41, SH2B3, TET2 and NF1 (Figure 1). Summary/Conclusion: This study shows that NGS panels may incidentally detect inherited variants related to predisposition to MN despite not having been designed for that purpose. Our data supports the importance of considering variants incidentally found upon tumor-only sequencing as potentially of germline origin. Indeed, one third of our cohort was suspicious of carrying a germline variant. We could confirm as inherited 100% of tested variants from patients with non-myeloid tissue available. For patients with follow-up data, VAF may help in discriminating ambiguous variants, but ultimately germline tissue sequencing is needed to determine the nature of the variant. These findings suggest that there is an increasing need for germline tissue testing along with the appropriate genetic counseling associated to it.\n

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\n \n\n \n \n \n \n \n \n Acquired BRAF G469A Mutation as a Resistance Mechanism to First-Line Osimertinib Treatment in NSCLC Cell Lines Harboring an EGFR Exon 19 Deletion.\n \n \n \n \n\n\n \n La Monica, S.; Minari, R.; Cretella, D.; Bonelli, M.; Fumarola, C.; Cavazzoni, A.; Galetti, M.; Digiacomo, G.; Riccardi, F.; Petronini, P. G.; Tiseo, M.; and Alfieri, R.\n\n\n \n\n\n\n Targeted Oncology, 14(5): 619–626. October 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Acquired$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{la_monica_acquired_2019,\n\ttitle = {Acquired {BRAF} {G469A} {Mutation} as a {Resistance} {Mechanism} to {First}-{Line} {Osimertinib} {Treatment} in {NSCLC} {Cell} {Lines} {Harboring} an {EGFR} {Exon} 19 {Deletion}},\n\tvolume = {14},\n\tissn = {1776-260X},\n\turl = {https://doi.org/10.1007/s11523-019-00669-x},\n\tdoi = {10.1007/s11523-019-00669-x},\n\tlanguage = {en},\n\tnumber = {5},\n\turldate = {2020-02-11},\n\tjournal = {Targeted Oncology},\n\tauthor = {La Monica, Silvia and Minari, Roberta and Cretella, Daniele and Bonelli, Mara and Fumarola, Claudia and Cavazzoni, Andrea and Galetti, Maricla and Digiacomo, Graziana and Riccardi, Federica and Petronini, Pier Giorgio and Tiseo, Marcello and Alfieri, Roberta},\n\tmonth = oct,\n\tyear = {2019},\n\tkeywords = {BRAF, Commercial, EGFR, Genomics, Illumina Sequencer, Oncology, SOPHiA DDM, STS, Solid Tumor, Targeted},\n\tpages = {619--626},\n}\n\n

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\n \n\n \n \n \n \n \n \n A Pediatric Case of Glioblastoma Multiforme Associated With a Novel Germline p.His112CysfsTer9 Mutation in the MLH1 Gene Accompanied by a p.Arg283Cys Mutation in the TP53 Gene: A Case Report.\n \n \n \n \n\n\n \n Stajkovska, A.; Mehandziska, S.; Rosalia, R.; Stavrevska, M.; Janevska, M.; Markovska, M.; Kungulovski, I.; Mitrev, Z.; and Kungulovski, G.\n\n\n \n\n\n\n Frontiers in Genetics, 10. October 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{stajkovska_pediatric_2019,\n\ttitle = {A {Pediatric} {Case} of {Glioblastoma} {Multiforme} {Associated} {With} a {Novel} {Germline} p.{His112CysfsTer9} {Mutation} in the {MLH1} {Gene} {Accompanied} by a p.{Arg283Cys} {Mutation} in the {TP53} {Gene}: {A} {Case} {Report}},\n\tvolume = {10},\n\tissn = {1664-8021},\n\tshorttitle = {A {Pediatric} {Case} of {Glioblastoma} {Multiforme} {Associated} {With} a {Novel} {Germline} p.{His112CysfsTer9} {Mutation} in the {MLH1} {Gene} {Accompanied} by a p.{Arg283Cys} {Mutation} in the {TP53} {Gene}},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842924/},\n\tdoi = {10.3389/fgene.2019.00952},\n\turldate = {2020-02-11},\n\tjournal = {Frontiers in Genetics},\n\tauthor = {Stajkovska, Aleksandra and Mehandziska, Sanja and Rosalia, Rodney and Stavrevska, Margarita and Janevska, Marija and Markovska, Martina and Kungulovski, Ivan and Mitrev, Zan and Kungulovski, Goran},\n\tmonth = oct,\n\tyear = {2019},\n\tpmid = {31749828},\n\tpmcid = {PMC6842924},\n\tkeywords = {Blood, Genomics, Hereditary Disorders, MLH1, SOPHiA DDM, TP53, Targeted, TruSight},\n}\n\n

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\n \n\n \n \n \n \n \n \n Alu element insertion in the MLH1 exon 6 coding sequence as a mutation predisposing to Lynch syndrome.\n \n \n \n \n\n\n \n Solassol, J.; Larrieux, M.; Leclerc, J.; Ducros, V.; Corsini, C.; Chiésa, J.; Pujol, P.; and Rey, J.\n\n\n \n\n\n\n Human Mutation, 40(6): 716–720. February 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Alu$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{solassol_alu_2019,\n\ttitle = {Alu element insertion in the {MLH1} exon 6 coding sequence as a mutation predisposing to {Lynch} syndrome},\n\tvolume = {40},\n\tissn = {1098-1004},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/humu.23725},\n\tdoi = {10.1002/humu.23725},\n\tabstract = {Lynch syndrome (LS) is the most frequent cause of hereditary colorectal cancer. A subset of patients with a history of LS shows no causal germline pathogenic alteration and are identified as having Lynch-like syndrome (LLS). Alu retrotransposons are the most abundant mobile DNA sequences in the human genome and have been associated with numerous human cancers by either disrupting coding regions or altering epigenetic modifications or splicing signals. We report a family first classified as having LLS by Sanger sequencing analysis. Next-generation sequencing (NGS) analysis identified an AluY5a insertion in MLH1 exon 6 that led to exon skipping. This splicing alteration inducing a pathogenic frameshift was found in patients who developed colorectal adenocarcinomas. Retroelement insertion might thus be an important but underestimated mechanism of cancer genetics that could be systematically tested in patients with a phenotype suggesting LS to accurately assess family risk and surveillance approaches.},\n\tlanguage = {en},\n\tnumber = {6},\n\turldate = {2020-02-11},\n\tjournal = {Human Mutation},\n\tauthor = {Solassol, Jérôme and Larrieux, Marion and Leclerc, Julie and Ducros, Vincent and Corsini, Carole and Chiésa, Jean and Pujol, Pascal and Rey, Jean-Marc},\n\tmonth = feb,\n\tyear = {2019},\n\tkeywords = {Alu, Blood, Genomics, HCS, Hereditary Disorders, Lynch syndrome},\n\tpages = {716--720},\n}\n\n

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\n \n\n \n \n \n \n \n \n Opportunistic testing of BRCA1, BRCA2 and mismatch repair genes improves the yield of phenotype driven hereditary cancer gene panels.\n \n \n \n \n\n\n \n Feliubadaló, L.; López‐Fernández, A.; Pineda, M.; Díez, O.; Valle, J. d.; Gutiérrez‐Enríquez, S.; Teulé, A.; González, S.; Stjepanovic, N.; Salinas, M.; Capellá, G.; Brunet, J.; Lázaro, C.; and Balmaña, J.\n\n\n \n\n\n\n International Journal of Cancer, 145(10): 2682–2691. March 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Opportunistic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{feliubadalo_opportunistic_2019,\n\ttitle = {Opportunistic testing of {BRCA1}, {BRCA2} and mismatch repair genes improves the yield of phenotype driven hereditary cancer gene panels},\n\tvolume = {145},\n\tcopyright = {© 2019 UICC},\n\tissn = {1097-0215},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.32304},\n\tdoi = {10.1002/ijc.32304},\n\tabstract = {Multigene panels provide a powerful tool for analyzing several genes simultaneously. We evaluated the frequency of pathogenic variants (PV) in customized predefined panels according to clinical suspicion by phenotype and compared it to the yield obtained in the analysis of our clinical research gene panel. We also investigated mutational yield of opportunistic testing of BRCA1/2 and mismatch repair (MMR) genes in all patients. A total of 1,205 unrelated probands with clinical suspicion of hereditary cancer were screened for germline mutations using panel testing. Overall, 1,048 females and 157 males were analyzed, mean age at cancer diagnosis was 48; 883 had hereditary breast/ovarian cancer-suspicion, 205 hereditary nonpolyposis colorectal cancer (HNPCC)-suspicion, 73 adenomatous-polyposis-suspicion and 44 with other/multiple clinical criteria. At least one PV was found in 150 probands (12\\%) analyzed by our customized phenotype-driven panel. Tumoral MMR deficiency predicted for the presence of germline MMR gene mutations in patients with HNPCC-suspicion (46/136 vs. 0/56 in patients with and without MMR deficiency, respectively). Opportunistic testing additionally identified five MSH6, one BRCA1 and one BRCA2 carriers (0.6\\%). The analysis of the extended 24-gene panel provided 25 additional PVs (2\\%), including in 4 out of 51 individuals harboring MMR-proficient colorectal tumors (2 CHEK2 and 2 ATM). Phenotype-based panels provide a notable rate of PVs with clinical actionability. Opportunistic testing of MMR and BRCA genes leads to a significant straightforward identification of MSH6, BRCA1 and BRCA2 mutation carriers, and endorses the model of opportunistic testing of genes with clinical utility within a standard genetic counseling framework.},\n\tlanguage = {en},\n\tnumber = {10},\n\turldate = {2020-02-11},\n\tjournal = {International Journal of Cancer},\n\tauthor = {Feliubadaló, Lídia and López‐Fernández, Adrià and Pineda, Marta and Díez, Orland and Valle, Jesús del and Gutiérrez‐Enríquez, Sara and Teulé, Alex and González, Sara and Stjepanovic, Neda and Salinas, Mónica and Capellá, Gabriel and Brunet, Joan and Lázaro, Conxi and Balmaña, Judith},\n\tmonth = mar,\n\tyear = {2019},\n\tkeywords = {BRCA1, BRCA1/2, BRCA2, Genomics, Hereditary Disorders, SOPHiA DDM, actionability, cancer susceptibility, germline cancer panel},\n\tpages = {2682--2691},\n}\n\n

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\n \n\n \n \n \n \n \n \n Multiple urinary tract infections are associated with genotype and phenotype in adult polycystic kidney disease.\n \n \n \n \n\n\n \n Eroglu, E.; Kocyigit, I.; Cetin, M.; Zararsiz, G.; Imamoglu, H.; Bayramov, R.; Tastan, S.; Sipahioglu, M. H.; Tokgoz, B.; and Oymak, O.\n\n\n \n\n\n\n Clinical and Experimental Nephrology, 23(10): 1188–1195. October 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Multiple$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{eroglu_multiple_2019,\n\ttitle = {Multiple urinary tract infections are associated with genotype and phenotype in adult polycystic kidney disease},\n\tvolume = {23},\n\tissn = {1437-7799},\n\turl = {https://doi.org/10.1007/s10157-019-01752-3},\n\tdoi = {10.1007/s10157-019-01752-3},\n\tlanguage = {en},\n\tnumber = {10},\n\turldate = {2020-02-11},\n\tjournal = {Clinical and Experimental Nephrology},\n\tauthor = {Eroglu, Eray and Kocyigit, Ismail and Cetin, Mustafa and Zararsiz, Gokmen and Imamoglu, Hakan and Bayramov, Ruslan and Tastan, Sinem and Sipahioglu, Murat Hayri and Tokgoz, Bulent and Oymak, Oktay},\n\tmonth = oct,\n\tyear = {2019},\n\tkeywords = {Blood, Genomics, NES, Nephropathies, SOPHiA DDM},\n\tpages = {1188--1195},\n}\n\n

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\n \n\n \n \n \n \n \n \n Development of a Novel Orthotopic Primary Human Chordoma Xenograft Model: A Relevant Support for Future Research on Chordoma.\n \n \n \n \n\n\n \n Salle, H.; Pocard, M.; Lehmann-Che, J.; Bourthoumieu, S.; Labrousse, F.; Pimpie, C.; Lemnos, L.; Guichard, J.; Froelich, S.; and Adle-Biassette, H.\n\n\n \n\n\n\n Journal of Neuropathology & Experimental Neurology. November 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Development$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{salle_development_2019,\n\ttitle = {Development of a {Novel} {Orthotopic} {Primary} {Human} {Chordoma} {Xenograft} {Model}: {A} {Relevant} {Support} for {Future} {Research} on {Chordoma}},\n\tshorttitle = {Development of a {Novel} {Orthotopic} {Primary} {Human} {Chordoma} {Xenograft} {Model}},\n\turl = {https://academic.oup.com/jnen/advance-article/doi/10.1093/jnen/nlz121/5678768},\n\tdoi = {10.1093/jnen/nlz121},\n\tabstract = {Abstract.  Chordomas are slow-growing rare malignant neoplasms. The aim of this study was to establish a primary model of chordoma in the lumbosacral orthotopic},\n\tlanguage = {en},\n\turldate = {2020-02-11},\n\tjournal = {Journal of Neuropathology \\& Experimental Neurology},\n\tauthor = {Salle, Henri and Pocard, Marc and Lehmann-Che, Jacqueline and Bourthoumieu, Sylvie and Labrousse, François and Pimpie, Cynthia and Lemnos, Leslie and Guichard, Jean-Pierre and Froelich, Sebastien and Adle-Biassette, Homa},\n\tmonth = nov,\n\tyear = {2019},\n\tkeywords = {Dry Lab, FFPE, Fresh-Frozen, Genomics, Solid Tumor},\n}\n\n

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\n \n\n \n \n \n \n \n \n Diagnostic Challenge in PLIN1-Associated Familial Partial Lipodystrophy.\n \n \n \n \n\n\n \n Jéru, I.; Vantyghem, M.; Bismuth, E.; Cervera, P.; Barraud, S.; Auclair, M.; Vatier, C.; Lascols, O.; Savage, D. B.; and Vigouroux, C.\n\n\n \n\n\n\n The Journal of Clinical Endocrinology & Metabolism, 104(12): 6025–6032. December 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Diagnostic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{jeru_diagnostic_2019,\n\ttitle = {Diagnostic {Challenge} in {PLIN1}-{Associated} {Familial} {Partial} {Lipodystrophy}},\n\tvolume = {104},\n\tissn = {0021-972X},\n\turl = {https://academic.oup.com/jcem/article/104/12/6025/5523296},\n\tdoi = {10.1210/jc.2019-00849},\n\tabstract = {We have described novel heterozygous PLIN1 frameshift variants in the largest cohort of FPLD4 reported to date and provide a set of arguments for their pathogen},\n\tlanguage = {en},\n\tnumber = {12},\n\turldate = {2020-02-11},\n\tjournal = {The Journal of Clinical Endocrinology \\& Metabolism},\n\tauthor = {Jéru, Isabelle and Vantyghem, Marie-Christine and Bismuth, Elise and Cervera, Pascale and Barraud, Sara and Auclair, Martine and Vatier, Camille and Lascols, Olivier and Savage, David B. and Vigouroux, Corinne},\n\tmonth = dec,\n\tyear = {2019},\n\tkeywords = {Genomics, Hereditary Disorders, Illumina Sequencer, Metabolism, PLIN1, SOPHiA DDM, Targeted},\n\tpages = {6025--6032},\n}\n\n

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\n \n\n \n \n \n \n \n \n Genomic Landscape of Sporadic Retinitis Pigmentosa: Findings from 877 Spanish Cases.\n \n \n \n \n\n\n \n Martin-Merida, I.; Avila-Fernandez, A.; Del Pozo-Valero, M.; Blanco-Kelly, F.; Zurita, O.; Perez-Carro, R.; Aguilera-Garcia, D.; Riveiro-Alvarez, R.; Arteche, A.; and Trujillo-Tiebas, M. J.\n\n\n \n\n\n\n Ophthalmology, 126(8): 1181–1188. August 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Genomic$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{martin-merida_genomic_2019,\n\ttitle = {Genomic {Landscape} of {Sporadic} {Retinitis} {Pigmentosa}: {Findings} from 877 {Spanish} {Cases}},\n\tvolume = {126},\n\tshorttitle = {Genomic {Landscape} of {Sporadic} {Retinitis} {Pigmentosa}},\n\turl = {https://www.aaojournal.org/article/S0161-6420(18)33392-X/fulltext},\n\tnumber = {8},\n\tjournal = {Ophthalmology},\n\tauthor = {Martin-Merida, Inmaculada and Avila-Fernandez, Almudena and Del Pozo-Valero, Marta and Blanco-Kelly, Fiona and Zurita, Olga and Perez-Carro, Raquel and Aguilera-Garcia, Domingo and Riveiro-Alvarez, Rosa and Arteche, Ana and Trujillo-Tiebas, Maria Jose},\n\tmonth = aug,\n\tyear = {2019},\n\tkeywords = {CES, CNV, De Novo, Exome, Genomics, Hereditary Disorders, MLPA, Ophthalmology, SNV, SOPHiA DDM, Sporadic Retinitis Pigmentosa, sRP},\n\tpages = {1181--1188},\n}\n\n

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\n \n\n \n \n \n \n \n \n Cinacalcet sustainedly prevents pancreatitis in a child with a compound heterozygous SPINK1/AP2S1 mutation.\n \n \n \n \n\n\n \n Scheers, I.; Sokal, E.; Limaye, N.; Denoncin, C.; Stephenne, X.; Pirson, Y.; and Godefroid, N.\n\n\n \n\n\n\n Pancreatology, 19(6): 801–804. September 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Cinacalcet$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{scheers_cinacalcet_2019,\n\ttitle = {Cinacalcet sustainedly prevents pancreatitis in a child with a compound heterozygous {SPINK1}/{AP2S1} mutation},\n\tvolume = {19},\n\turl = {https://www.sciencedirect.com/science/article/abs/pii/S1424390319306799},\n\tnumber = {6},\n\tjournal = {Pancreatology},\n\tauthor = {Scheers, Isabelle and Sokal, Etienne and Limaye, Nisha and Denoncin, C. and Stephenne, Xavier and Pirson, Y. and Godefroid, Nathalie},\n\tmonth = sep,\n\tyear = {2019},\n\tkeywords = {AP2S1, Blood, Bundle, Case Study, Custom, Custom Panel, Genomics, Hereditary Disorders, Illumina Sequencer, Liquid Biopsy, Metabolism, Pancreatitis, SOPHiA DDM, SPINK1, Targeted},\n\tpages = {801--804},\n}\n\n

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\n \n\n \n \n \n \n \n \n Next-generation sequencing for JAK2 mutation testing: advantages and pitfalls.\n \n \n \n \n\n\n \n Maslah, N.; Verger, E.; Schlageter, M.; Miclea, J.; Kiladjian, J.; Giraudier, S.; Chomienne, C.; and Cassinat, B.\n\n\n \n\n\n\n Annals of Hematology, 98(1): 111–118. January 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Next-generation$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{maslah_next-generation_2019,\n\ttitle = {Next-generation sequencing for {JAK2} mutation testing: advantages and pitfalls},\n\tvolume = {98},\n\tissn = {1432-0584},\n\tshorttitle = {Next-generation sequencing for {JAK2} mutation testing},\n\turl = {https://doi.org/10.1007/s00277-018-3499-y},\n\tdoi = {10.1007/s00277-018-3499-y},\n\tabstract = {The JAK2V617F mutation is part of the major criteria for diagnosis of myeloproliferative neoplasms (MPN). Allele-specific quantitative PCR (qPCR) is the most prevalent method used in laboratories but with the advent of next-generation sequencing (NGS) techniques, we felt necessary to evaluate this approach for JAK2 mutations testing. Among DNA samples from 427 patients analyzed by qPCR and NGS, we found an excellent concordance between both methods when allelic burden was superior to 2\\% (the detection limit of our NGS assay). Only one sample among 298 was found negative by NGS while allelic burden by qPCR was 3\\%. Because NGS detection limit is higher, sensitivity was lower as exemplified by 21 samples found negative whereas qPCR measured allelic burdens between 0.1 and 1\\%. Importantly, quantitative data of samples found positive by both techniques were highly correlated (R2 = 0.9477). We also evaluated 40 samples tested for JAK2 exon 12 mutations by HRM. The concordance with NGS was of 100\\%. Using NGS, the full coding region of JAK2 was analyzed leading to identification of several variants outside of exon 12 and 14 which were previously described or not. Interestingly, we found one somatic mutation (c.1034A{\\textgreater}T p.H345L) which induced constitutive activation of the JAK/STAT pathway leading to an increased proliferation of BaF/3 cells with low-dose EPO. This study showed that NGS is a robust method highly correlated to qPCR, although less sensitive, but providing the opportunity to identify other JAK2 variants with potential impact on disease initiation or evolution.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2020-02-11},\n\tjournal = {Annals of Hematology},\n\tauthor = {Maslah, Nabih and Verger, Emmanuelle and Schlageter, Marie-Helene and Miclea, Jean-Michel and Kiladjian, Jean-Jacques and Giraudier, Stephane and Chomienne, Christine and Cassinat, Bruno},\n\tmonth = jan,\n\tyear = {2019},\n\tkeywords = {Custom, Genomics, Illumina Sequencer, JAK2, Liquid Biopsy, Liquid tumor, Oncology, Solid Tumor, Targeted},\n\tpages = {111--118},\n}\n\n

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\n \n\n \n \n \n \n \n \n Third generation EGFR inhibitor osimertinib combined with pemetrexed or cisplatin exerts long-lasting anti-tumor effect in EGFR-mutated pre-clinical models of NSCLC.\n \n \n \n \n\n\n \n La Monica, S.; Minari, R.; Cretella, D.; Flammini, L.; Fumarola, C.; Bonelli, M.; Cavazzoni, A.; Digiacomo, G.; Galetti, M.; and Madeddu, D.\n\n\n \n\n\n\n Journal of Experimental & Clinical Cancer Research, 38(1): 222. May 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Third$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{la_monica_third_2019,\n\ttitle = {Third generation {EGFR} inhibitor osimertinib combined with pemetrexed or cisplatin exerts long-lasting anti-tumor effect in {EGFR}-mutated pre-clinical models of {NSCLC}},\n\tvolume = {38},\n\turl = {https://jeccr.biomedcentral.com/articles/10.1186/s13046-019-1240-x},\n\tnumber = {1},\n\tjournal = {Journal of Experimental \\& Clinical Cancer Research},\n\tauthor = {La Monica, Silvia and Minari, Roberta and Cretella, Daniele and Flammini, Lisa and Fumarola, Claudia and Bonelli, Mara and Cavazzoni, Andrea and Digiacomo, Graziana and Galetti, Maricla and Madeddu, Denise},\n\tmonth = may,\n\tyear = {2019},\n\tkeywords = {Clinical study, EGFR, Genomics, INDEL, NSCLC, Non-Small Cell Lung Cancer, SOPHiA DDM, STS, Solid Tumor, osimertinib},\n\tpages = {222},\n}\n\n

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\n \n\n \n \n \n \n \n \n Achondrogenesis type 2 in a newborn with a novel mutation on the COL2A1 gene.\n \n \n \n \n\n\n \n Dogan, P.; Varal, I. G.; Gorukmez, O.; Akkurt, M. O.; and Akdag, A.\n\n\n \n\n\n\n Balkan journal of medical genetics: BJMG, 22(1): 89. August 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Achondrogenesis$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{dogan_achondrogenesis_2019,\n\ttitle = {Achondrogenesis type 2 in a newborn with a novel mutation on the {COL2A1} gene},\n\tvolume = {22},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714336/},\n\tnumber = {1},\n\tjournal = {Balkan journal of medical genetics: BJMG},\n\tauthor = {Dogan, P. and Varal, I. G. and Gorukmez, O. and Akkurt, M. O. and Akdag, A.},\n\tmonth = aug,\n\tyear = {2019},\n\tkeywords = {Blood, CES, COL2A1, Case Study, Genomics, Rare disease, SOPHiA DDM},\n\tpages = {89},\n}\n\n

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\n \n\n \n \n \n \n \n \n ADA2 Deficiency: Case Series of Five Patients with Varying Phenotypes.\n \n \n \n \n\n\n \n Tanatar, A.; Karadağ, Ş. G.; Sözeri, B.; Sönmez, H. E.; Çakan, M.; Demirkol, Y. K.; and Ayaz, N. A.\n\n\n \n\n\n\n Journal of Clinical Immunology,1–6. December 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"ADA2$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{tanatar_ada2_2019,\n\ttitle = {{ADA2} {Deficiency}: {Case} {Series} of {Five} {Patients} with {Varying} {Phenotypes}},\n\tshorttitle = {{ADA2} {Deficiency}},\n\turl = {https://link.springer.com/article/10.1007/s10875-019-00734-0},\n\tjournal = {Journal of Clinical Immunology},\n\tauthor = {Tanatar, Ayşe and Karadağ, Şerife Gül and Sözeri, Betül and Sönmez, Hafize Emine and Çakan, Mustafa and Demirkol, Yasemin Kendir and Ayaz, Nuray Aktay},\n\tmonth = dec,\n\tyear = {2019},\n\tkeywords = {ADA2, Adenosine Deaminase 2 Deficiency, Blood, Case Study, Genomics, Hereditary Disorders, SOPHiA DDM, SOPHiA Fever \\& Auto Inflammatory Diseases},\n\tpages = {1--6},\n}\n\n

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\n \n\n \n \n \n \n \n \n Aportación de la secuenciación masiva de nueva generación en el diagnóstico del síndrome de cáncer de mama y ovario hereditario mediante el uso de un panel de genes.\n \n \n \n \n\n\n \n Castillo Guardiola, V.\n\n\n \n\n\n\n Proyecto de investigación:. July 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Aportación$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{castillo_guardiola_aportacion_2019,\n\ttitle = {Aportación de la secuenciación masiva de nueva generación en el diagnóstico del síndrome de cáncer de mama y ovario hereditario mediante el uso de un panel de genes},\n\turl = {https://digitum.um.es/digitum/handle/10201/73883},\n\tjournal = {Proyecto de investigación:},\n\tauthor = {Castillo Guardiola, Verónica},\n\tmonth = jul,\n\tyear = {2019},\n\tkeywords = {Breast cancer, Genomics, Ovarian Cancer, Solid Tumor},\n}\n\n

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\n \n\n \n \n \n \n \n \n Clinical and genetic description of patients with prenatally identified cardiac tumors.\n \n \n \n \n\n\n \n Mariscal-Mendizábal, L. F.; Sevilla-Montoya, R.; Martínez-García, A. J.; Alaez-Verson, C.; Monroy-Muñoz, I. E.; Pérez-Durán, J.; Cerón-Albarrán, J. A.; Carrillo-Sánchez, K.; Molina-Garay, C.; and Flores-Lagunes, L. L.\n\n\n \n\n\n\n Prenatal diagnosis, 39(11): 998–1004. July 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Clinical$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{mariscal-mendizabal_clinical_2019,\n\ttitle = {Clinical and genetic description of patients with prenatally identified cardiac tumors},\n\tvolume = {39},\n\turl = {https://obgyn.onlinelibrary.wiley.com/doi/abs/10.1002/pd.5521},\n\tnumber = {11},\n\tjournal = {Prenatal diagnosis},\n\tauthor = {Mariscal-Mendizábal, Luisa F. and Sevilla-Montoya, Rosalba and Martínez-García, Alfonso J. and Alaez-Verson, Carmen and Monroy-Muñoz, Irma E. and Pérez-Durán, Javier and Cerón-Albarrán, Jorge A. and Carrillo-Sánchez, Karol and Molina-Garay, Carolina and Flores-Lagunes, Luis L.},\n\tmonth = jul,\n\tyear = {2019},\n\tkeywords = {Blood, Cardiology, Genomics, Hereditary Disorders, Rhabdomyoma, SOPHiA DDM, TSC, Tuberous Sclerosis Complex},\n\tpages = {998--1004},\n}\n\n

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\n \n\n \n \n \n \n \n \n Clinical exome sequencing identifies two novel mutations of the SCN1A and SCN2A genes in Moroccan patients with epilepsy: a case series.\n \n \n \n \n\n\n \n Sahli, M.; Zrhidri, A.; Elaloui, S. C.; Smaili, W.; Lyahyai, J.; Oudghiri, F. Z.; and Sefiani, A.\n\n\n \n\n\n\n Journal of medical case reports, 13(1): 266. August 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Clinical$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{sahli_clinical_2019,\n\ttitle = {Clinical exome sequencing identifies two novel mutations of the {SCN1A} and {SCN2A} genes in {Moroccan} patients with epilepsy: a case series},\n\tvolume = {13},\n\tshorttitle = {Clinical exome sequencing identifies two novel mutations of the {SCN1A} and {SCN2A} genes in {Moroccan} patients with epilepsy},\n\turl = {https://link.springer.com/article/10.1186/s13256-019-2203-8},\n\tnumber = {1},\n\tjournal = {Journal of medical case reports},\n\tauthor = {Sahli, Maryem and Zrhidri, Abdelali and Elaloui, Siham Chafai and Smaili, Wiam and Lyahyai, Jaber and Oudghiri, Fatima Zohra and Sefiani, Abdelaziz},\n\tmonth = aug,\n\tyear = {2019},\n\tkeywords = {CES, Case Study, De Novo, Epilepsy, Exome, Genomics, SCN1A, SCN2A, SOPHiA DDM},\n\tpages = {266},\n}\n\n

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\n \n\n \n \n \n \n \n \n Desarrollo y validación de un protocolo de bajo costo para la detección de mutaciones somáticas en los oncogenes KRAS, NRAS y EGFR por NGS.\n \n \n \n \n\n\n \n Russo Cappi, V.\n\n\n \n\n\n\n . May 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Desarrollo$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{russo_cappi_desarrollo_2019,\n\ttitle = {Desarrollo y validación de un protocolo de bajo costo para la detección de mutaciones somáticas en los oncogenes {KRAS}, {NRAS} y {EGFR} por {NGS}},\n\turl = {https://www.colibri.udelar.edu.uy/jspui/bitstream/20.500.12008/22383/1/uy24-19434.pdf},\n\tauthor = {Russo Cappi, Valentina},\n\tmonth = may,\n\tyear = {2019},\n\tkeywords = {Blood, Colorectal Cancer, EGFR, FFPE, Genomics, KRAS, Lung Cancer, NRAS, SOPHiA DDM, Solid Tumor},\n}\n\n

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\n \n\n \n \n \n \n \n \n EP. 20ANO5-related myopathy: report of the first Greek patients.\n \n \n \n \n\n\n \n Svingou, M.; Kekou, K.; Papadopoulos, C.; Xirou, S.; Kararizou, E.; and Papadimas, G.\n\n\n \n\n\n\n Neuromuscular Disorders, 29: S75–S76. October 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"EP.$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{svingou_ep_2019,\n\ttitle = {{EP}. {20ANO5}-related myopathy: report of the first {Greek} patients},\n\tvolume = {29},\n\tshorttitle = {{EP}. {20ANO5}-related myopathy},\n\turl = {https://www.nmd-journal.com/article/S0960-8966(19)30538-3/abstract},\n\tjournal = {Neuromuscular Disorders},\n\tauthor = {Svingou, M. and Kekou, K. and Papadopoulos, C. and Xirou, S. and Kararizou, E. and Papadimas, G.},\n\tmonth = oct,\n\tyear = {2019},\n\tkeywords = {ANO5, Abstract, Exome, Genetic Muscle Disease, Genomics, SOPHiA DDM, Targeted},\n\tpages = {S75--S76},\n}\n\n

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\n \n\n \n \n \n \n \n \n Evaluation of KRAS, NRAS and BRAF hotspot mutations detection for patients with metastatic colorectal cancer using direct DNA pipetting in a fully-automated platform and Next-Generation Sequencing for laboratory workflow optimisation.\n \n \n \n \n\n\n \n Gilson, P.; Franczak, C.; Dubouis, L.; Husson, M.; Rouyer, M.; Demange, J.; Perceau, M.; Leroux, A.; Merlin, J.; and Harlé, A.\n\n\n \n\n\n\n PloS one, 14(7). July 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Evaluation$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{gilson_evaluation_2019,\n\ttitle = {Evaluation of {KRAS}, {NRAS} and {BRAF} hotspot mutations detection for patients with metastatic colorectal cancer using direct {DNA} pipetting in a fully-automated platform and {Next}-{Generation} {Sequencing} for laboratory workflow optimisation},\n\tvolume = {14},\n\turl = {https://journals.plos.org/plosone/article/file?type=printable&id=10.1371/journal.pone.0219204},\n\tnumber = {7},\n\tjournal = {PloS one},\n\tauthor = {Gilson, Pauline and Franczak, Claire and Dubouis, Ludovic and Husson, Marie and Rouyer, Marie and Demange, Jessica and Perceau, Marie and Leroux, Agnès and Merlin, Jean-Louis and Harlé, Alexandre},\n\tmonth = jul,\n\tyear = {2019},\n\tkeywords = {BRAF, FFPE, Genomics, KRAS, NRAS, SOPHiA DDM, Solid Tumor},\n}\n\n

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\n \n\n \n \n \n \n \n \n Genotypic and phenotypic evolution in a patient with chronic myelomonocytic leukemia.\n \n \n \n \n\n\n \n Geissler, K.; Jäger, E.; and Gurbisz, M.\n\n\n \n\n\n\n Leukemia Research Reports, 12: 100185. October 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Genotypic$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{geissler_genotypic_2019,\n\ttitle = {Genotypic and phenotypic evolution in a patient with chronic myelomonocytic leukemia},\n\tvolume = {12},\n\turl = {https://www.sciencedirect.com/science/article/pii/S2213048919300482},\n\tjournal = {Leukemia Research Reports},\n\tauthor = {Geissler, Klaus and Jäger, Eva and Gurbisz, Michael},\n\tmonth = oct,\n\tyear = {2019},\n\tkeywords = {Blood, Bone Marrow, CMML, Case Study, Chronic Myelomonocytic Leukemia, Commercial, Genomics, Liquid Biopsy, Liquid tumor, MYS, SOPHiA DDM, Targeted},\n\tpages = {100185},\n}\n\n

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\n \n\n \n \n \n \n \n \n Glutathione synthetase deficiency: a novel mutation with femur agenesis.\n \n \n \n \n\n\n \n Guney Varal, I.; Dogan, P.; Gorukmez, O.; Dorum, S.; and Akdag, A.\n\n\n \n\n\n\n Fetal and Pediatric Pathology, 39(1): 38–44. June 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Glutathione$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{guney_varal_glutathione_2019,\n\ttitle = {Glutathione synthetase deficiency: a novel mutation with femur agenesis},\n\tvolume = {39},\n\tshorttitle = {Glutathione synthetase deficiency},\n\turl = {https://www.tandfonline.com/doi/abs/10.1080/15513815.2019.1627627},\n\tnumber = {1},\n\tjournal = {Fetal and Pediatric Pathology},\n\tauthor = {Guney Varal, Ipek and Dogan, Pelin and Gorukmez, Orhan and Dorum, Sevil and Akdag, Arzu},\n\tmonth = jun,\n\tyear = {2019},\n\tkeywords = {Blood, CES, Case Study, GSS, Genomics, Hereditary Disorders, SOPHiA DDM},\n\tpages = {38--44},\n}\n\n

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\n \n\n \n \n \n \n \n \n Implementation of massive sequencing in the genetic diagnosis of hereditary cancer syndromes: diagnostic performance in the Hereditary Cancer Programme of the Valencia Community (FamCan-NGS).\n \n \n \n \n\n\n \n Ramírez-Calvo, M.; García-Casado, Z.; Fernández-Serra, A.; de Juan, I.; Palanca, S.; Oltra, S.; Soto, J. L.; Castillejo, A.; Barbera, V. M.; and Juan-Fita, M. J.\n\n\n \n\n\n\n Hereditary cancer in clinical practice, 17(1): 3. January 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Implementation$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{ramirez-calvo_implementation_2019,\n\ttitle = {Implementation of massive sequencing in the genetic diagnosis of hereditary cancer syndromes: diagnostic performance in the {Hereditary} {Cancer} {Programme} of the {Valencia} {Community} ({FamCan}-{NGS})},\n\tvolume = {17},\n\tshorttitle = {Implementation of massive sequencing in the genetic diagnosis of hereditary cancer syndromes},\n\turl = {https://link.springer.com/article/10.1186/s13053-019-0104-x},\n\tnumber = {1},\n\tjournal = {Hereditary cancer in clinical practice},\n\tauthor = {Ramírez-Calvo, Marta and García-Casado, Zaida and Fernández-Serra, Antonio and de Juan, Inmaculada and Palanca, Sarai and Oltra, Silvestre and Soto, José Luis and Castillejo, Adela and Barbera, Víctor M. and Juan-Fita, Ma José},\n\tmonth = jan,\n\tyear = {2019},\n\tkeywords = {Genomics, HCS, Hereditary Disorders, SNV, SOPHiA DDM, Targeted},\n\tpages = {3},\n}\n\n

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\n \n\n \n \n \n \n \n \n 21 Prevalence of BRCA1/2 mutation and alterations of homologous recombination deficiency (HRD) in uterine leiomyosarcoma: a retrospective, monocentric study.\n \n \n \n \n\n\n \n Ciccarone, F.; Ferrandina, G.; Zannoni, G. F.; Angelico, G.; Capoluongo, E.; and Scambia, G.\n\n\n \n\n\n\n BMJ Specialist Journals, September 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"21$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@book{ciccarone_21_2019,\n\ttitle = {21 {Prevalence} of {BRCA1}/2 mutation and alterations of homologous recombination deficiency ({HRD}) in uterine leiomyosarcoma: a retrospective, monocentric study},\n\tshorttitle = {21 {Prevalence} of {BRCA1}/2 mutation and alterations of homologous recombination deficiency ({HRD}) in uterine leiomyosarcoma},\n\turl = {https://ijgc.bmj.com/content/29/Suppl_3/A13.1?int_source=trendmd&int_medium=cpc&int_campaign=usage},\n\tpublisher = {BMJ Specialist Journals},\n\tauthor = {Ciccarone, F. and Ferrandina, G. and Zannoni, G. F. and Angelico, G. and Capoluongo, E. and Scambia, G.},\n\tmonth = sep,\n\tyear = {2019},\n\tkeywords = {Commercial, FFPE, Genomics, Oncology, Solid Tumor, Targeted, miniHRS},\n}\n\n

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\n \n\n \n \n \n \n \n \n Genomic characterization in triple-negative primary myelofibrosis and other myeloid neoplasms with bone marrow fibrosis.\n \n \n \n \n\n\n \n Alvarez-Larrán, A.; López-Guerra, M.; Rozman, M.; Correa, J.; Hernández-Boluda, J. C.; Tormo, M.; Martínez, D.; Martín, I.; Colomer, D.; Esteve, J.; and Cervantes, F.\n\n\n \n\n\n\n Annals of Hematology, 98(10): 2319–2328. October 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Genomic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{alvarez-larran_genomic_2019,\n\ttitle = {Genomic characterization in triple-negative primary myelofibrosis and other myeloid neoplasms with bone marrow fibrosis},\n\tvolume = {98},\n\tissn = {1432-0584},\n\turl = {https://doi.org/10.1007/s00277-019-03766-z},\n\tdoi = {10.1007/s00277-019-03766-z},\n\tabstract = {Triple-negative primary myelofibrosis (TN-PMF) and other myeloid neoplasms with associated bone marrow fibrosis such as the myelodysplastic syndromes (MDS-F) or the myelodysplastic/myeloproliferative neoplasms (MDS/MPN-F) are rare entities, often difficult to distinguish from each other. Thirty-four patients previously diagnosed with TN-PMF (n = 14), MDS-F (n = 18), or MDS/MPN-F (n = 2) were included in the present study. After central revision of the bone marrow histology, diagnoses according to the 2016-WHO classification were TN-PMF (n = 6), MDS-F (n = 19), and MDS/MPN-F (n = 9), with TN-PMF genotype representing only 4\\% of a cohort of 141 molecularly annotated PMF. Genomic classification according to next-generation sequencing and cytogenetic study was performed in 28 cases. Median number of mutations was 4 (range 1–7) in cases with TP53 disruption/aneuploidy or with chromatin-spliceosome mutations versus 1 mutation (range 0–2) in other molecular subgroups (p {\\textless} 0.0001). The number of mutations and the molecular classification were better than PMF and MDS conventional scoring systems to predict survival and progression to acute leukemia. In conclusion, TN-PMF is an uncommon entity when the 2016 WHO criteria are strictly applied. Genomic classification may help in the prognostic assessment of patients with myeloid neoplasms with bone marrow fibrosis.},\n\tlanguage = {en},\n\tnumber = {10},\n\turldate = {2020-02-11},\n\tjournal = {Annals of Hematology},\n\tauthor = {Alvarez-Larrán, Alberto and López-Guerra, Mónica and Rozman, María and Correa, Juan-Gonzalo and Hernández-Boluda, Juan Carlos and Tormo, Mar and Martínez, Daniel and Martín, Iván and Colomer, Dolors and Esteve, Jordi and Cervantes, Francisco},\n\tmonth = oct,\n\tyear = {2019},\n\tkeywords = {Commercial, Genomics, Illumina Sequencer, Liquid Biopsy, Liquid tumor, MYS, Oncology, Targeted},\n\tpages = {2319--2328},\n}\n\n

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\n \n\n \n \n \n \n \n \n PERIL MUTACIONAL EN PACIENTES CON LEUCEMIA MIELOIDE AGUDA MEDIANTE SECUENCIACIÓN DE PRÓXIMA GENERACIÓN.\n \n \n \n \n\n\n \n Carandino, M. V.; Jacome, O. J.; and Montanaro, P. C.\n\n\n \n\n\n\n . November 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"PERIL$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{carandino_peril_2019,\n\ttitle = {{PERIL} {MUTACIONAL} {EN} {PACIENTES} {CON} {LEUCEMIA} {MIELOIDE} {AGUDA} {MEDIANTE} {SECUENCIACIÓN} {DE} {PRÓXIMA} {GENERACIÓN}},\n\turl = {https://cobico.com.ar/wp-content/archivos/2019/11/leucemia.pdf},\n\tauthor = {Carandino, María Virginia and Jacome, Oscar Javier and Montanaro, Patricia Cristina},\n\tmonth = nov,\n\tyear = {2019},\n\tkeywords = {Blood, Bundle, Genomics, Illumina Sequencer, Liquid Biopsy, Liquid tumor, Oncology, SOPHiA DDM, Targeted},\n}\n\n

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\n \n\n \n \n \n \n \n \n β-Catenin nuclear expression discriminates deep penetrating nevi from other cutaneous melanocytic tumors.\n \n \n \n \n\n\n \n de la Fouchardière, A.; Caillot, C.; Jacquemus, J.; Durieux, E.; Houlier, A.; Haddad, V.; and Pissaloux, D.\n\n\n \n\n\n\n Virchows Archiv, 474(5): 539–550. February 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"β-Catenin$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{de_la_fouchardiere_-catenin_2019,\n\ttitle = {β-{Catenin} nuclear expression discriminates deep penetrating nevi from other cutaneous melanocytic tumors},\n\tvolume = {474},\n\turl = {https://link.springer.com/article/10.1007/s00428-019-02533-9},\n\tnumber = {5},\n\tjournal = {Virchows Archiv},\n\tauthor = {de la Fouchardière, Arnaud and Caillot, Claire and Jacquemus, Julien and Durieux, Emeline and Houlier, Aurélie and Haddad, Véronique and Pissaloux, Daniel},\n\tmonth = feb,\n\tyear = {2019},\n\tkeywords = {Case Study, FFPE, Genomics, Illumina Sequencer, MiniSeq, SOPHiA DDM, STS, Solid Tumor},\n\tpages = {539--550},\n}\n\n

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\n \n\n \n \n \n \n \n \n Clinical validation of NGS workflow in myeloid neoplasms.\n \n \n \n \n\n\n \n Bourgne, C.; Berger, M.; and Kurze, A.\n\n\n \n\n\n\n Journal of Clinical Oncology, 37(15_suppl): e18557–e18557. May 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Clinical$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{bourgne_clinical_2019,\n\ttitle = {Clinical validation of {NGS} workflow in myeloid neoplasms.},\n\tvolume = {37},\n\tissn = {0732-183X},\n\turl = {https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.e18557},\n\tdoi = {10.1200/JCO.2019.37.15_suppl.e18557},\n\tnumber = {15\\_suppl},\n\turldate = {2020-02-11},\n\tjournal = {Journal of Clinical Oncology},\n\tauthor = {Bourgne, Céline and Berger, Marc and Kurze, Alexander},\n\tmonth = may,\n\tyear = {2019},\n\tkeywords = {Blood, Genomics, MYS, Targeted},\n\tpages = {e18557--e18557},\n}\n\n

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\n \n\n \n \n \n \n \n \n Liquid Biopsy Is Useful to Identify the Genetic Profile of NHL-B at Diagnosis in Different Histological Subtypes.\n \n \n \n \n\n\n \n Bastos-Oreiro, M.; Suárez González, J.; Carrión, N. C.; Andres, C.; Moreno, S.; Carbonell, D.; Chicano Lavilla, M.; Oarbeascoa, G.; Diaz Crespo, F.; Menarguez, J.; Díez-Martín, J. L.; Buño, I.; and Martínez-Laperche, C.\n\n\n \n\n\n\n Blood, 134(Supplement_1): 5216–5216. November 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Liquid$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{bastos-oreiro_liquid_2019,\n\ttitle = {Liquid {Biopsy} {Is} {Useful} to {Identify} the {Genetic} {Profile} of {NHL}-{B} at {Diagnosis} in {Different} {Histological} {Subtypes}},\n\tvolume = {134},\n\tissn = {0006-4971},\n\turl = {https://ashpublications.org/blood/article/134/Supplement_1/5216/425268/Liquid-Biopsy-Is-Useful-to-Identify-the-Genetic},\n\tdoi = {10.1182/blood-2019-129868},\n\tlanguage = {en},\n\tnumber = {Supplement\\_1},\n\turldate = {2020-02-11},\n\tjournal = {Blood},\n\tauthor = {Bastos-Oreiro, Mariana and Suárez González, Julia and Carrión, Natalia Carolina and Andres, Cristina and Moreno, Solsireey and Carbonell, Diego and Chicano Lavilla, María and Oarbeascoa, Gillen and Diaz Crespo, Francisco and Menarguez, Javier and Díez-Martín, José Luis and Buño, Ismael and Martínez-Laperche, Carolina},\n\tmonth = nov,\n\tyear = {2019},\n\tkeywords = {Benchmark, Commercial, FFPE, Genomics, Illumina Sequencer, LYS, Liquid Biopsy, Liquid tumor, Oncology, SOPHiA DDM, Targeted},\n\tpages = {5216--5216},\n}\n\n

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\n \n\n \n \n \n \n \n \n Erdheim-Chester disease associated with chronic myelomonocytic leukemia harboring the same clonal mutation.\n \n \n \n \n\n\n \n Bonnet, P.; Chasset, F.; Moguelet, P.; Abisror, N.; Itzykson, R.; Bouaziz, J.; Hirsch, P.; Barbaud, A.; Haroche, J.; and Mekinian, A.\n\n\n \n\n\n\n haematologica, 104(11): e530. November 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Erdheim-Chester$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{bonnet_erdheim-chester_2019,\n\ttitle = {Erdheim-{Chester} disease associated with chronic myelomonocytic leukemia harboring the same clonal mutation},\n\tvolume = {104},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821636/},\n\tnumber = {11},\n\tjournal = {haematologica},\n\tauthor = {Bonnet, Pauline and Chasset, François and Moguelet, Philippe and Abisror, Noémie and Itzykson, Raphaël and Bouaziz, Jean-David and Hirsch, Pierre and Barbaud, Annick and Haroche, Julien and Mekinian, Arsène},\n\tmonth = nov,\n\tyear = {2019},\n\tkeywords = {Genomics, Liquid Biopsy, Liquid tumor, SOPHiA DDM, Targeted},\n\tpages = {e530},\n}\n\n

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\n \n\n \n \n \n \n \n \n Fri0556 Genetic Screening in Patients with Undifferentiated Periodic Fever Syndrome.\n \n \n \n \n\n\n \n Demir, F.; Doğan, Ö. A.; Kendirci, Y.; Tekkus, K. E.; Canbek, S.; Ayaz, N. A.; Doğanay, L.; and Sözeri, B.\n\n\n \n\n\n\n Annals of the Rheumatic Diseases, 78(Suppl 2): 974–974. June 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Fri0556$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{demir_fri0556_2019,\n\ttitle = {Fri0556 {Genetic} {Screening} in {Patients} with {Undifferentiated} {Periodic} {Fever} {Syndrome}},\n\tvolume = {78},\n\tcopyright = {© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.},\n\tissn = {0003-4967, 1468-2060},\n\turl = {https://ard.bmj.com/content/78/Suppl_2/974.1},\n\tdoi = {10.1136/annrheumdis-2019-eular.7907},\n\tlanguage = {en},\n\tnumber = {Suppl 2},\n\turldate = {2020-02-11},\n\tjournal = {Annals of the Rheumatic Diseases},\n\tauthor = {Demir, Ferhat and Doğan, Özlem Akgün and Kendirci, Yasemin and Tekkus, Kubra Ermis and Canbek, Sezin and Ayaz, Nuray Aktay and Doğanay, Levent and Sözeri, Betül},\n\tmonth = jun,\n\tyear = {2019},\n\tpages = {974--974},\n}\n\n

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\n \n\n \n \n \n \n \n \n Thumb duplication: molecular analysis of different clinical types.\n \n \n \n \n\n\n \n Kyriazis, Z.; Kollia, P.; Grivea, I.; Varitimidis, S. E.; Constantoulakis, P.; and Dailiana, Z. H.\n\n\n \n\n\n\n European Journal of Orthopaedic Surgery & Traumatology, 29(2): 421–426. February 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Thumb$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{kyriazis_thumb_2019,\n\ttitle = {Thumb duplication: molecular analysis of different clinical types},\n\tvolume = {29},\n\tissn = {1432-1068},\n\tshorttitle = {Thumb duplication},\n\turl = {https://doi.org/10.1007/s00590-018-2343-3},\n\tdoi = {10.1007/s00590-018-2343-3},\n\tabstract = {PurposeMolecular analysis of different types of thumb duplication and identification of new suspected gene mutations.Materials and methodsIn a series of patients operated for polydactyly, DNA was extracted from blood samples collected preoperatively. Among these, the samples of two patients with thumb duplication (Wassel types III and IV) were initially selected for molecular analysis. The method of Clinical Exome Solution was used for the study of the phenotype-involved genes. Next-generation sequencing (NGS) was performed on a NextSeq-500 Platform (Illumina), and Sophia DDM® SaaS algorithms were used for the bioinformatics analysis of the data.ResultsIn total, 8—including 4 new—mutations were detected in CEP290 (1 mutation), RPGRIP1 (2 mutations), TMEM216 (2 mutations), FBN1 (1 mutation), CEP164 (1 mutation), and MEGF8 (1 mutation) genes. NGS revealed 3 mutated genes in the patient with Wassel III thumb duplication and 5 mutated genes in the patient with Wassel IV duplication. The molecular analysis revealed that the patients had 2 mutated genes in common, but they only shared one common mutation.ConclusionThe new detected mutations are most probably associated with thumb duplication, as they belong to genes with already described mutations causing ciliopathies, often including polydactyly in their phenotype. Recognition of these mutations will be helpful to prenatal diagnosis, operative treatment strategy prediction, and possible future experimental applications in gene therapy.},\n\tlanguage = {en},\n\tnumber = {2},\n\turldate = {2020-02-11},\n\tjournal = {European Journal of Orthopaedic Surgery \\& Traumatology},\n\tauthor = {Kyriazis, Zisis and Kollia, Panagoula and Grivea, Ioanna and Varitimidis, Sokratis E. and Constantoulakis, Pantelis and Dailiana, Zoe H.},\n\tmonth = feb,\n\tyear = {2019},\n\tkeywords = {Commercial, Genomic Hereditary Disorders, Illumina Sequencer, Large panel, Liquid Biopsy, SOPHiA DDM},\n\tpages = {421--426},\n}\n\n

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\n \n\n \n \n \n \n \n \n Phenotypic variability including Behçet's disease-like manifestations in DADA2 patients due to a homozygous c.973-2A\\textgreaterG splice site mutation.\n \n \n \n \n\n\n \n \n\n\n \n\n\n\n December 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Phenotypic$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@misc{noauthor_phenotypic_2019,\n\ttitle = {Phenotypic variability including {Behçet}'s disease-like manifestations in {DADA2} patients due to a homozygous c.973-{2A}{\\textgreater}{G} splice site mutation},\n\turl = {https://www.clinexprheumatol.org/abstract.asp?a=14623},\n\tlanguage = {en-GB},\n\turldate = {2020-02-11},\n\tjournal = {Clin Exp Rheumatol},\n\tmonth = dec,\n\tyear = {2019},\n}\n\n

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\n \n\n \n \n \n \n \n \n A De Novo Heterozygous Variant (HBB: c. 379delG, p. Val127Cysfs* 32) Associated with a Mild β-Thalassemia Intermedia Phenotype in a Turkish Child.\n \n \n \n \n\n\n \n Gürlek-Gökçebay, D.; Akpinar-Tekgunduz, S.; Erdem, H. B.; and Yarali, N.\n\n\n \n\n\n\n Hemoglobin, 43(4-5): 277–279. September 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{gurlek-gokcebay_novo_2019,\n\ttitle = {A {De} {Novo} {Heterozygous} {Variant} ({HBB}: c. {379delG}, p. {Val127Cysfs}* 32) {Associated} with a {Mild} β-{Thalassemia} {Intermedia} {Phenotype} in a {Turkish} {Child}},\n\tvolume = {43},\n\tshorttitle = {A {De} {Novo} {Heterozygous} {Variant} ({HBB}},\n\turl = {https://www.tandfonline.com/doi/abs/10.1080/03630269.2019.1660888},\n\tnumber = {4-5},\n\tjournal = {Hemoglobin},\n\tauthor = {Gürlek-Gökçebay, Dilek and Akpinar-Tekgunduz, Sibel and Erdem, Haktan B. and Yarali, Nese},\n\tmonth = sep,\n\tyear = {2019},\n\tkeywords = {Bundle, Case Study, Genomic Hereditary Disorders, Large panel, SOPHiA DDM},\n\tpages = {277--279},\n}\n\n

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\n \n\n \n \n \n \n \n \n Revisiting CLEC 12A as leukaemic stem cell marker in AML: highlighting the necessity of precision diagnostics in patients eligible for targeted therapy.\n \n \n \n \n\n\n \n Bill, M.; Aggerholm, A.; Kjeldsen, E.; Roug, A. S.; Hokland, P.; and Nederby, L.\n\n\n \n\n\n\n British journal of haematology, 184(5): 769–781. March 2019.\n \n\n\n\n
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@article{bill_revisiting_2019,\n\ttitle = {Revisiting {CLEC} {12A} as leukaemic stem cell marker in {AML}: highlighting the necessity of precision diagnostics in patients eligible for targeted therapy},\n\tvolume = {184},\n\tshorttitle = {Revisiting {CLEC} {12A} as leukaemic stem cell marker in {AML}},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1111/bjh.15711},\n\tnumber = {5},\n\tjournal = {British journal of haematology},\n\tauthor = {Bill, Marie and Aggerholm, Anni and Kjeldsen, Eigil and Roug, Anne S. and Hokland, Peter and Nederby, Line},\n\tmonth = mar,\n\tyear = {2019},\n\tpages = {769--781},\n}\n\n

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\n \n\n \n \n \n \n \n \n EP. 22Anti-HMGCR antibody in asymptomatic patients with high CK-Case report.\n \n \n \n \n\n\n \n Soares, I.; Comprido, V.; Hsu, B.; Turke, K.; Silva, L.; Feder, D.; and Carvalho, A.\n\n\n \n\n\n\n Neuromuscular Disorders, 29: S76. October 2019.\n \n\n\n\n
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@article{soares_ep_2019,\n\ttitle = {{EP}. {22Anti}-{HMGCR} antibody in asymptomatic patients with high {CK}-{Case} report},\n\tvolume = {29},\n\turl = {https://www.nmd-journal.com/article/S0960-8966(19)30540-1/abstract},\n\tjournal = {Neuromuscular Disorders},\n\tauthor = {Soares, I. and Comprido, V. and Hsu, B. and Turke, K. and Silva, L. and Feder, D. and Carvalho, A.},\n\tmonth = oct,\n\tyear = {2019},\n\tpages = {S76},\n}\n\n

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\n \n\n \n \n \n \n \n \n EP. 23A novel LMNA mutation identified in an Argentinian patient with autosomal dominant Emery-Dreifuss muscular dystrophy phenotype.\n \n \n \n \n\n\n \n Azcona, C.; Bettini, M.; Belziti, C.; Brogger, M.; and Rugiero, M.\n\n\n \n\n\n\n Neuromuscular Disorders, 29: S76–S77. October 2019.\n \n\n\n\n
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@article{azcona_ep_2019,\n\ttitle = {{EP}. {23A} novel {LMNA} mutation identified in an {Argentinian} patient with autosomal dominant {Emery}-{Dreifuss} muscular dystrophy phenotype},\n\tvolume = {29},\n\turl = {https://www.nmd-journal.com/article/S0960-8966(19)30541-3/abstract},\n\tjournal = {Neuromuscular Disorders},\n\tauthor = {Azcona, C. and Bettini, M. and Belziti, C. and Brogger, M. and Rugiero, M.},\n\tmonth = oct,\n\tyear = {2019},\n\tpages = {S76--S77},\n}\n\n

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\n \n\n \n \n \n \n \n \n EP. 21Bcl-2-associated athanogene-3 (BAG3) myopathy in an ethnic-Indian Malaysian patient.\n \n \n \n \n\n\n \n Goh, K.; Low, S.; Mun, K.; Tan, C.; Shahrizaila, N.; Nishino, I.; and Wong, K.\n\n\n \n\n\n\n Neuromuscular Disorders, 29: S76. October 2019.\n \n\n\n\n
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@article{goh_ep_2019,\n\ttitle = {{EP}. {21Bcl}-2-associated athanogene-3 ({BAG3}) myopathy in an ethnic-{Indian} {Malaysian} patient},\n\tvolume = {29},\n\turl = {https://www.nmd-journal.com/article/S0960-8966(19)30539-5/abstract},\n\tjournal = {Neuromuscular Disorders},\n\tauthor = {Goh, K. and Low, S. and Mun, K. and Tan, C. and Shahrizaila, N. and Nishino, I. and Wong, K.},\n\tmonth = oct,\n\tyear = {2019},\n\tpages = {S76},\n}\n\n

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\n \n\n \n \n \n \n \n \n Clinical characteristics and genetic profiles of young and adult patients with cholestatic liver disease.\n \n \n \n \n\n\n \n Huynh, M.; Nguyen, T.; Grison, S.; Lascols, O.; Fernandez, E.; and Barbu, V.\n\n\n \n\n\n\n Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva, 111. October 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Clinical$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{huynh_clinical_2019,\n\ttitle = {Clinical characteristics and genetic profiles of young and adult patients with cholestatic liver disease.},\n\tvolume = {111},\n\turl = {https://online.reed.es/DOI/PDF/ArticuloDOI_6168.pdf},\n\tjournal = {Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva},\n\tauthor = {Huynh, Minh-Tuan and Nguyen, Truong-Tam and Grison, Sophie and Lascols, Olivier and Fernandez, Eric and Barbu, Véronique},\n\tmonth = oct,\n\tyear = {2019},\n}\n\n

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\n \n\n \n \n \n \n \n \n Novel mutations and deletions in cystic fibrosis in a tertiary cystic fibrosis center in Istanbul.\n \n \n \n \n\n\n \n Atag, E.; Ikizoglu, N. B.; Ergenekon, A. P.; Gokdemir, Y.; Eralp, E. E.; Ata, P.; Ersu, R.; Karakoc, F.; and Karadag, B.\n\n\n \n\n\n\n Pediatric Pulmonology, 54(6): 743–750. April 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Novel$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n

@article{atag_novel_2019,\n\ttitle = {Novel mutations and deletions in cystic fibrosis in a tertiary cystic fibrosis center in {Istanbul}},\n\tvolume = {54},\n\tcopyright = {© 2019 Wiley Periodicals, Inc.},\n\tissn = {1099-0496},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/ppul.24299},\n\tdoi = {10.1002/ppul.24299},\n\tabstract = {Background Cystic fibrosis (CF) genotyping has garnered increased attention since the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989 led to the identification of over 1700 mutations on chromosome 7. Yet, little is known about the genetic profile of CF patients in Turkey. This study sought to determine the mutation distribution among CF patients seeking care at Marmara University. Methods Two hundred fifty previously diagnosed CF patients were included in the study. CFTR gene exons 1 to 27 were amplified by a polymerase chain reaction and whole DNA sequencing was performed. Duplications and deletions were investigated by the multiplex ligation-dependent probe amplification (MLPA) technique in patients with one or two unidentified mutations in sequence analysis. Results CFTR mutation analysis revealed 80 mutations and five large deletions were present in our study population. The five most common mutations were (delta) F508 (c.1521-1523delCTT) (28.4\\%), 1677delTA (c.1545-1546delTA) (6.4\\%), 2789 + 5G- {\\textgreater} A (c.2657 + 5G {\\textgreater} A) (5.8\\%), N1303K (c.3909C {\\textgreater} G) (2.4\\%), and c.2183AA- {\\textgreater} G (c.2051-2052delAAinsG) (4.0\\%). Large deletions were found in 16 patients. Four novel mutations and two novel deletions were detected in this study. Conclusions We have identified four novel mutations and two novel deletions using next-generation DNA sequencing and the MLPA technique and obtained an overall mutation detection rate of 91.4\\%. Detection of novel variants in CF patients will assist in genetic counseling and in determining appropriate patients for new therapies.},\n\tlanguage = {en},\n\tnumber = {6},\n\turldate = {2020-02-11},\n\tjournal = {Pediatric Pulmonology},\n\tauthor = {Atag, Emine and Ikizoglu, Nilay Bas and Ergenekon, Almala Pinar and Gokdemir, Yasemin and Eralp, Ela Erdem and Ata, Pinar and Ersu, Refika and Karakoc, Fazilet and Karadag, Bulent},\n\tmonth = apr,\n\tyear = {2019},\n\tkeywords = {cystic fibrosis, genetics, pulmonology},\n\tpages = {743--750},\n}\n\n\n\n\n

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\n \n\n \n \n \n \n \n \n In silico prediction of the pathogenic effect of a novel variant of BCKDHA leading to classical maple syrup urine disease identified using clinical exome sequencing.\n \n \n \n \n\n\n \n Fernández-Lainez, C.; Aláez-Verson, C.; Ibarra-González, I.; Enríquez-Flores, S.; Carrillo-Sanchez, K.; Flores-Lagunes, L.; Guillén-López, S.; Belmont-Martínez, L.; and Vela-Amieva, M.\n\n\n \n\n\n\n Clinica Chimica Acta, 483: 33–38. August 2018.\n \n\n\n\n
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@article{fernandez-lainez_silico_2018,\n\ttitle = {In silico prediction of the pathogenic effect of a novel variant of {BCKDHA} leading to classical maple syrup urine disease identified using clinical exome sequencing},\n\tvolume = {483},\n\turl = {https://www.sciencedirect.com/science/article/abs/pii/S0009898118301876},\n\tjournal = {Clinica Chimica Acta},\n\tauthor = {Fernández-Lainez, Cynthia and Aláez-Verson, Carmen and Ibarra-González, Isabel and Enríquez-Flores, Sergio and Carrillo-Sanchez, Karol and Flores-Lagunes, Leonardo and Guillén-López, Sara and Belmont-Martínez, Leticia and Vela-Amieva, Marcela},\n\tmonth = aug,\n\tyear = {2018},\n\tkeywords = {BCKDHA, Blood, Bundle, CES, Case Study, Genomics, Hereditary Disorders, Illumina Sequencer, Large panel, Liquid Biopsy, MSUD, Maple Syrup Urine Disease, Metabolism, SOPHiA DDM},\n\tpages = {33--38},\n}\n\n

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\n \n\n \n \n \n \n \n \n Sviluppo di un percorso diagnostico mediante tecnologia NGS per la caratterizazione molecolare di pazienti atasso spastici e pazienti con fenotipi neurologici complessi.\n \n \n \n \n\n\n \n Campopiano, R.\n\n\n \n\n\n\n . January 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"Sviluppo$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{campopiano_sviluppo_2018,\n\ttitle = {Sviluppo di un percorso diagnostico mediante tecnologia {NGS} per la caratterizazione molecolare di pazienti atasso spastici e pazienti con fenotipi neurologici complessi},\n\turl = {https://iris.unimol.it/retrieve/handle/11695/86513/84224/Tesi_R_Campopiano.pdf},\n\tauthor = {Campopiano, Rosa},\n\tmonth = jan,\n\tyear = {2018},\n\tkeywords = {Ataxia, Blood, CES, Genomics, Neurological Phenotype, Rare disease, SOPHiA DDM, Spasticity},\n}\n\n

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\n \n\n \n \n \n \n \n \n Single-cell whole exome and targeted sequencing in NPM1/FLT3 positive pediatric acute myeloid leukemia.\n \n \n \n \n\n\n \n Walter, C.; Pozzorini, C.; Reinhardt, K.; Geffers, R.; Xu, Z.; Reinhardt, D.; von Neuhoff, N.; and Hanenberg, H.\n\n\n \n\n\n\n Pediatric Blood & Cancer, 65(2). February 2018.\n \n\n\n\n
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@article{walter_single-cell_2018,\n\ttitle = {Single-cell whole exome and targeted sequencing in {NPM1}/{FLT3} positive pediatric acute myeloid leukemia},\n\tvolume = {65},\n\tissn = {1545-5017},\n\turl = {https://www.ncbi.nlm.nih.gov/pubmed/29090521},\n\tdoi = {10.1002/pbc.26848},\n\tabstract = {BACKGROUND: The small portion of leukemic stem cells (LSCs) in acute myeloid leukemia (AML) present in children and adolescents is often masked by the high background of AML blasts and normal hematopoietic cells. The aim of the current study was to establish a simple workflow for reliable genetic analysis of single LSC-enriched blasts from pediatric patients.\nPROCEDURE: For three AMLs with mutations in nucleophosmin 1 and/or fms-like tyrosine kinase 3, we performed whole genome amplification on sorted single-cell DNA followed by whole exome sequencing (WES). The corresponding bulk bone marrow DNAs were also analyzed by WES and by targeted sequencing (TS) that included 54 genes associated with myeloid malignancies.\nRESULTS: Analysis revealed that read coverage statistics were comparable between single-cell and bulk WES data, indicating high-quality whole genome amplification. From 102 single-cell variants, 72 single nucleotide variants and insertions or deletions (70\\%) were consistently found in the two bulk DNA analyses. Variants reliably detected in single cells were also present in TS. However, initial screening by WES with read counts between 50-72× failed to detect rare AML subclones in the bulk DNAs.\nCONCLUSIONS: In summary, our study demonstrated that single-cell WES combined with bulk DNA TS is a promising tool set for detecting AML subclones and possibly LSCs.},\n\tlanguage = {eng},\n\tnumber = {2},\n\tjournal = {Pediatric Blood \\& Cancer},\n\tauthor = {Walter, Christiane and Pozzorini, Christian and Reinhardt, Katarina and Geffers, Robert and Xu, Zhenyu and Reinhardt, Dirk and von Neuhoff, Nils and Hanenberg, Helmut},\n\tmonth = feb,\n\tyear = {2018},\n\tpmid = {29090521},\n\tkeywords = {AML, Acute myeloid leukemia, Exome, Genomics, INDEL, Pediatrics, Rare disease, SNV, SOPHiA DDM, Single-Cell Analysis, Targeted},\n}\n\n

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\n \n\n \n \n \n \n \n \n A Whole Germline BRCA2 Gene Deletion: How to Learn from CNV In Silico Analysis.\n \n \n \n \n\n\n \n Scaglione, G. L.; Concolino, P.; De Bonis, M.; De Paolis, E.; Minucci, A.; Ferrandina, G.; Scambia, G.; and Capoluongo, E.\n\n\n \n\n\n\n International Journal of Molecular Sciences, 19(4): 961. April 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{scaglione_whole_2018,\n\ttitle = {A {Whole} {Germline} {BRCA2} {Gene} {Deletion}: {How} to {Learn} from {CNV} {In} {Silico} {Analysis}},\n\tvolume = {19},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tshorttitle = {A {Whole} {Germline} {BRCA2} {Gene} {Deletion}},\n\turl = {https://www.mdpi.com/1422-0067/19/4/961},\n\tdoi = {10.3390/ijms19040961},\n\tabstract = {BRCA1/2 screening in Hereditary Breast and Ovarian Syndrome (HBOC) is an essential step for effective patients’ management. Next-Generation Sequencing (NGS) can rapidly provide high throughput and reliable information about the qualitative and quantitative status of tumor-associated genes. Straightforwardly, bioinformatics methods play a key role in molecular diagnostics pipelines. BRCA1/2 genes were evaluated with our NGS workflow, coupled with Multiplex Amplicon Quantification (MAQ) and Multiplex Ligation-dependent Probe Amplification (MLPA) assays. Variant calling was performed on Amplicon Suite, while Copy Number Variant (CNV) prediction by in house and commercial CNV tools, before confirmatory MAQ/MLPA testing. The germline profile of BRCA genes revealed a unique HBOC pattern. Although variant calling analysis pinpointed heterozygote and homozygote polymorphisms on BRCA1 and BRCA2, respectively, the CNV predicted by our script suggested two conflicting interpretations: BRCA1 duplication and/or BRCA2 deletion. Our commercial software reported a BRCA1 duplication, in contrast with variant calling results. Finally, the MAQ/MLPA assays assessed a whole BRCA2 copy loss. In silico CNV analysis is a time and cost-saving procedure to powerfully identify possible Large Rearrangements using robust and efficient NGS pipelines. Our layout shows as bioinformatics algorithms alone cannot completely and correctly identify whole BRCA1/2 deletions/duplications. In particular, the complete deletion of an entire gene, like in our case, cannot be solved without alternative strategies as MLPA/MAQ. These findings support the crucial role of bioinformatics in deciphering pitfalls within NGS data analysis.},\n\tlanguage = {en},\n\tnumber = {4},\n\turldate = {2020-02-11},\n\tjournal = {International Journal of Molecular Sciences},\n\tauthor = {Scaglione, Giovanni Luca and Concolino, Paola and De Bonis, Maria and De Paolis, Elisa and Minucci, Angelo and Ferrandina, Gabriella and Scambia, Giovanni and Capoluongo, Ettore},\n\tmonth = apr,\n\tyear = {2018},\n\tkeywords = {BRCA2, Blood, CNV, Genomics, Hereditary Disorders, Illumina Sequencer, SOPHiA DDM, Targeted},\n\tpages = {961},\n}\n\n

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\n \n\n \n \n \n \n \n \n Cutaneous Melanocytoma With CRTC1-TRIM11 Fusion.\n \n \n \n \n\n\n \n Cellier, L.; Perron, E.; Pissaloux, D.; Karanian, M.; Haddad, V.; Alberti, L.; and de la Fouchardière, A.\n\n\n \n\n\n\n March 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"Cutaneous$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@misc{cellier_cutaneous_2018,\n\ttype = {Text},\n\ttitle = {Cutaneous {Melanocytoma} {With} {CRTC1}-{TRIM11} {Fusion}},\n\turl = {https://www.ingentaconnect.com/content/wk/ajsp/2018/00000042/00000003/art00015},\n\tlanguage = {en},\n\turldate = {2020-02-11},\n\tauthor = {Cellier, Lucie and Perron, Emilie and Pissaloux, Daniel and Karanian, Marie and Haddad, Veronique and Alberti, Laurent and de la Fouchardière, Arnaud},\n\tmonth = mar,\n\tyear = {2018},\n\tdoi = {info:doi/10.1097/PAS.0000000000000996},\n\tkeywords = {CRTC1, Fusion, Genomics, Solid Tumor, TRIM11},\n}\n\n

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\n \n\n \n \n \n \n \n \n Somatic mutations as markers of outcome after azacitidine and allogeneic stem cell transplantation in higher-risk myelodysplastic syndromes.\n \n \n \n \n\n\n \n Falconi, G.; Fabiani, E.; Piciocchi, A.; Criscuolo, M.; Fianchi, L.; Lindfors Rossi, E. L.; Finelli, C.; Cerqui, E.; Ottone, T.; Molteni, A.; Parma, M.; Santarone, S.; Candoni, A.; Sica, S.; Leone, G.; Lo-Coco, F.; and Voso, M. T.\n\n\n \n\n\n\n Leukemia, 33(3): 785–790. October 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"Somatic$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{falconi_somatic_2018,\n\ttitle = {Somatic mutations as markers of outcome after azacitidine and allogeneic stem cell transplantation in higher-risk myelodysplastic syndromes},\n\tvolume = {33},\n\tcopyright = {2018 The Author(s)},\n\tissn = {1476-5551},\n\turl = {https://www.nature.com/articles/s41375-018-0284-9},\n\tdoi = {10.1038/s41375-018-0284-9},\n\tlanguage = {en},\n\tnumber = {3},\n\turldate = {2020-02-11},\n\tjournal = {Leukemia},\n\tauthor = {Falconi, Giulia and Fabiani, Emiliano and Piciocchi, Alfonso and Criscuolo, Marianna and Fianchi, Luana and Lindfors Rossi, Elisa L. and Finelli, Carlo and Cerqui, Elisa and Ottone, Tiziana and Molteni, Alfredo and Parma, Matteo and Santarone, Stella and Candoni, Anna and Sica, Simona and Leone, Giuseppe and Lo-Coco, Francesco and Voso, Maria Teresa},\n\tmonth = oct,\n\tyear = {2018},\n\tkeywords = {Allogeneic Stem Cell Transplantation, Clinical study, Genomics, Liquid tumor, MDS, MYS, Myelodysplastic syndromes, Somatic Mutations},\n\tpages = {785--790},\n}\n\n

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\n \n\n \n \n \n \n \n \n Ruxolitinib in elderly patients with myelofibrosis: impact of age and genotype. A multicentre study on 291 elderly patients.\n \n \n \n \n\n\n \n Palandri, F.; Catani, L.; Bonifacio, M.; Benevolo, G.; Heidel, F.; Palumbo, G. A.; Crugnola, M.; Abruzzese, E.; Bartoletti, D.; Polverelli, N.; Bergamaschi, M.; Tiribelli, M.; Iurlo, A.; Breccia, M.; Cavazzini, F.; Tieghi, A.; Binotto, G.; Isidori, A.; Martino, B.; D'Adda, M.; Bosi, C.; Sabattini, E.; Vitolo, U.; Aversa, F.; Ibatici, A.; Lemoli, R. M.; Sgherza, N.; Cuneo, A.; Martinelli, G.; Semenzato, G.; Cavo, M.; Vianelli, N.; Sapienza, M. R.; and Latagliata, R.\n\n\n \n\n\n\n British Journal of Haematology, 183(1): 35–46. July 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"Ruxolitinib$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{palandri_ruxolitinib_2018,\n\ttitle = {Ruxolitinib in elderly patients with myelofibrosis: impact of age and genotype. {A} multicentre study on 291 elderly patients},\n\tvolume = {183},\n\tcopyright = {© 2018 British Society for Haematology and John Wiley \\& Sons Ltd},\n\tissn = {1365-2141},\n\tshorttitle = {Ruxolitinib in elderly patients with myelofibrosis},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1111/bjh.15497},\n\tdoi = {10.1111/bjh.15497},\n\tabstract = {Ruxolitinib is a JAK1/2 inhibitor that may control myelofibrosis (MF)-related splenomegaly and symptoms and can be prescribed regardless of age. While aging is known to correlate with worse prognosis, no specific analysis is available to confirm that ruxolitinib is suitable for use in older populations. A clinical database was created in 23 European Haematology Centres and retrospective data on 291 MF patients treated with ruxolitinib when aged ≥65 years were analysed in order to assess the impact of age and molecular genotype on responses, toxicities and survival. Additional mutations were evaluated by a next generation sequencing (NGS) approach in 69 patients with available peripheral blood samples at the start of ruxolitinib treatment. Compared to older (age 65–74 years) patients, elderly (≥75 years) showed comparable responses to ruxolitinib, but higher rates of drug-induced anaemia and thrombocytopenia and worse survival. Nonetheless, the ruxolitinib discontinuation rate was comparable in the two age groups. Number and types of molecular abnormalities were comparable across age groups. However, the presence of high molecular risk (HMR) mutations significantly affected survival, counterbalancing the effect of aging. Indeed, elderly patients with {\\textless}2 HMR mutated genes had a comparable survival to older patients with ≥2 HMR mutations. Given that responses were not influenced by age, older age per se should not be a limitation for ruxolitinib administration. NGS analysis of HMR mutations also confirmed a strong predictive value in elderly patients.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2020-02-11},\n\tjournal = {British Journal of Haematology},\n\tauthor = {Palandri, Francesca and Catani, Lucia and Bonifacio, Massimiliano and Benevolo, Giulia and Heidel, Florian and Palumbo, Giuseppe A. and Crugnola, Monica and Abruzzese, Elisabetta and Bartoletti, Daniela and Polverelli, Nicola and Bergamaschi, Micaela and Tiribelli, Mario and Iurlo, Alessandra and Breccia, Massimo and Cavazzini, Francesco and Tieghi, Alessia and Binotto, Gianni and Isidori, Alessandro and Martino, Bruno and D'Adda, Mariella and Bosi, Costanza and Sabattini, Elena and Vitolo, Umberto and Aversa, Franco and Ibatici, Adalberto and Lemoli, Roberto M. and Sgherza, Nicola and Cuneo, Antonio and Martinelli, Giovanni and Semenzato, Giampietro and Cavo, Michele and Vianelli, Nicola and Sapienza, Maria R. and Latagliata, Roberto},\n\tmonth = jul,\n\tyear = {2018},\n\tkeywords = {Blood, Clinical study, Genomics, HMR, High Molecular Risk Mutations, INDEL, MYS, Myelofibrosis, Ruxolitinib, SNV, SOPHiA DDM},\n\tpages = {35--46},\n}\n\n

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\n \n\n \n \n \n \n \n \n Triple Negative Myelofibrosis and Myelodysplastic Syndrome with Fibrosis: Clinico-Biological Characterization and Correlation with Gene Mutations.\n \n \n \n \n\n\n \n Correa, J. G.; Alvarez-Larrán, A.; Lopez-Guerra, M.; Hernandez Boluda, J. C.; Tormo, M.; Rozman, M.; Martínez, D.; Colomer, D.; Esteve, J.; and Cervantes, F.\n\n\n \n\n\n\n Blood, 132(Supplement 1): 4299–4299. November 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"Triple$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{correa_triple_2018,\n\ttitle = {Triple {Negative} {Myelofibrosis} and {Myelodysplastic} {Syndrome} with {Fibrosis}: {Clinico}-{Biological} {Characterization} and {Correlation} with {Gene} {Mutations}},\n\tvolume = {132},\n\tissn = {0006-4971},\n\tshorttitle = {Triple {Negative} {Myelofibrosis} and {Myelodysplastic} {Syndrome} with {Fibrosis}},\n\turl = {https://ashpublications.org/blood/article/132/Supplement 1/4299/275775/Triple-Negative-Myelofibrosis-and-Myelodysplastic},\n\tdoi = {10.1182/blood-2018-99-115888},\n\tlanguage = {en},\n\tnumber = {Supplement 1},\n\turldate = {2020-02-11},\n\tjournal = {Blood},\n\tauthor = {Correa, Juan Gonzalo and Alvarez-Larrán, Alberto and Lopez-Guerra, Monica and Hernandez Boluda, Juan Carlos and Tormo, Mar and Rozman, María and Martínez, Daniel and Colomer, Dolors and Esteve, Jordi and Cervantes, Francisco},\n\tmonth = nov,\n\tyear = {2018},\n\tkeywords = {F-MDS, Genomics, Liquid tumor, MYS, Poster, TN-PMF},\n\tpages = {4299--4299},\n}\n\n

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\n \n\n \n \n \n \n \n \n Identification of a BRCA2 mutation in a Turkish family with early‐onset breast cancer.\n \n \n \n \n\n\n \n Celik, E.; Ermis Tekkus, K.; Akcay, I. M.; Alkurt Sal, G.; Ezberci, F.; Dinler Doganay, G.; and Doganay, L.\n\n\n \n\n\n\n Clinical Case Reports, 6(9): 1751–1755. July 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"Identification$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{celik_identification_2018,\n\ttitle = {Identification of a {BRCA2} mutation in a {Turkish} family with early‐onset breast cancer},\n\tvolume = {6},\n\tissn = {2050-0904},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132100/},\n\tdoi = {10.1002/ccr3.1625},\n\tnumber = {9},\n\turldate = {2020-02-11},\n\tjournal = {Clinical Case Reports},\n\tauthor = {Celik, Elifnaz and Ermis Tekkus, Kubra and Akcay, Izzet Mehmet and Alkurt Sal, Gizem and Ezberci, Fikret and Dinler Doganay, Gizem and Doganay, Levent},\n\tmonth = jul,\n\tyear = {2018},\n\tpmid = {30214756},\n\tpmcid = {PMC6132100},\n\tkeywords = {BRCA2, Blood, Case Study, Genomics, Hereditary Disorders, SOPHiA DDM},\n\tpages = {1751--1755},\n}\n\n

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\n \n\n \n \n \n \n \n \n Cross-platform comparison for the detection of RAS mutations in cfDNA (ddPCR Biorad detection assay, BEAMing assay, and NGS strategy).\n \n \n \n \n\n\n \n Garcia, J.; Forestier, J.; Dusserre, E.; Wozny, A.; Geiguer, F.; Merle, P.; Tissot, C.; Ferraro-Peyret, C.; Jones, F. S.; Edelstein, D. L.; Cheynet, V.; Bardel, C.; Vilchez, G.; Xu, Z.; Bringuier, P. P.; Barritault, M.; Brengle-Pesce, K.; Guillet, M.; Chauvenet, M.; Manship, B.; Brevet, M.; Rodriguez-Lafrasse, C.; Hervieu, V.; Couraud, S.; Walter, T.; and Payen, L.\n\n\n \n\n\n\n Oncotarget, 9(30): 21122–21131. April 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"Cross-platform$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{garcia_cross-platform_2018,\n\ttitle = {Cross-platform comparison for the detection of {RAS} mutations in {cfDNA} ({ddPCR} {Biorad} detection assay, {BEAMing} assay, and {NGS} strategy)},\n\tvolume = {9},\n\tissn = {1949-2553},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940402/},\n\tdoi = {10.18632/oncotarget.24950},\n\tnumber = {30},\n\turldate = {2020-02-11},\n\tjournal = {Oncotarget},\n\tauthor = {Garcia, Jessica and Forestier, Julien and Dusserre, Eric and Wozny, Anne-Sophie and Geiguer, Florence and Merle, Patrick and Tissot, Claire and Ferraro-Peyret, Carole and Jones, Frederick S. and Edelstein, Daniel L. and Cheynet, Valérie and Bardel, Claire and Vilchez, Gaelle and Xu, Zhenyu and Bringuier, Pierre Paul and Barritault, Marc and Brengle-Pesce, Karen and Guillet, Marielle and Chauvenet, Marion and Manship, Brigitte and Brevet, Marie and Rodriguez-Lafrasse, Claire and Hervieu, Valérie and Couraud, Sébastien and Walter, Thomas and Payen, Léa},\n\tmonth = apr,\n\tyear = {2018},\n\tpmid = {29765524},\n\tpmcid = {PMC5940402},\n\tkeywords = {Blood, Colon Cancer, FFPE, Genomics, Liquid Biopsy, Lung Cancer, Solid Tumor, cfDNA},\n\tpages = {21122--21131},\n}\n\n

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\n \n\n \n \n \n \n \n \n Evaluation of a Next-Generation Sequencing Assay for BRCA1 and BRCA2 Mutation Detection.\n \n \n \n \n\n\n \n Capone, G. L.; Putignano, A. L.; Trujillo Saavedra, S.; Paganini, I.; Sestini, R.; Gensini, F.; De Rienzo, I.; Papi, L.; and Porfirio, B.\n\n\n \n\n\n\n The Journal of Molecular Diagnostics, 20(1): 87–94. January 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"Evaluation$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{capone_evaluation_2018,\n\ttitle = {Evaluation of a {Next}-{Generation} {Sequencing} {Assay} for {BRCA1} and {BRCA2} {Mutation} {Detection}},\n\tvolume = {20},\n\tissn = {1525-1578},\n\turl = {http://www.sciencedirect.com/science/article/pii/S1525157817303380},\n\tdoi = {10.1016/j.jmoldx.2017.09.005},\n\tabstract = {The efficiency of a novel targeted next-generation sequencing (NGS) test, the Devyser BRCA kit, for a comprehensive analysis of all 48 coding exons of the high-risk breast/ovarian cancer susceptibility genes BRCA1 and BRCA2 has been assessed. The new assay intended to detect nucleotide substitutions, small deletions/insertions, and large deletions/duplications. To document the false-negative and false-positive rates of the NGS assay in the hands of end users, 48 samples with previously identified 444 small variants and seven gross rearrangements were analyzed, showing 100\\% concordance with gold standards. Furthermore, all other 43 variants (42 single-nucleotide variation or insertion/deletion variation and one copy number variation, whose significance is or may be of clinical value), which were called by the NGS assay in a prospectively analyzed 179-sample set, were confirmed by Sanger sequencing or multiplex ligation probe amplification, according to their nature. We conclude that the Devyser BRCA kit performed satisfactorily for use in a clinical laboratory.},\n\tlanguage = {en},\n\tnumber = {1},\n\turldate = {2020-02-11},\n\tjournal = {The Journal of Molecular Diagnostics},\n\tauthor = {Capone, Gabriele Lorenzo and Putignano, Anna Laura and Trujillo Saavedra, Sharon and Paganini, Irene and Sestini, Roberta and Gensini, Francesca and De Rienzo, Irene and Papi, Laura and Porfirio, Berardino},\n\tmonth = jan,\n\tyear = {2018},\n\tkeywords = {BRCA1, BRCA1/2, BRCA2, Benchmark, Blood, Breast cancer, Bundle, CNV, Genomics, HBOC, Hereditary Disorders, INDEL, Illumina Sequencer, Liquid Biopsy, Oncology, Ovarian Cancer, SNV, SOPHiA DDM, Solid Tumor, Targeted},\n\tpages = {87--94},\n}\n\n

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\n \n\n \n \n \n \n \n \n First identification of homozygous truncating CSRP3 variants in two unrelated cases with hypertrophic cardiomyopathy.\n \n \n \n \n\n\n \n Janin, A.; Bessière, F.; Chauveau, S.; Chevalier, P.; and Millat, G.\n\n\n \n\n\n\n Gene, 676: 110–116. November 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"First$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{janin_first_2018,\n\ttitle = {First identification of homozygous truncating {CSRP3} variants in two unrelated cases with hypertrophic cardiomyopathy},\n\tvolume = {676},\n\tissn = {0378-1119},\n\turl = {http://www.sciencedirect.com/science/article/pii/S0378111918308102},\n\tdoi = {10.1016/j.gene.2018.07.036},\n\tabstract = {Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease with an estimated prevalence of 1/500. More than 40 genes have been reported to cause HCM. Among them, CSRP3 is usually included on HCM gene panels used for molecular diagnosis by next-generation sequencing (NGS). To provide new insights into the pathophysiology of hypertrophic cardiomyopathy, a NGS workflow based on a panel of 48 cardiomyopathies-causing genes was analyzed on a cohort of 542 HCM patients. As expected, this molecular approach led to identify most pathogenic or likely pathogenic variants into prevalent HCM-causing genes: MYBPC3 (123/542; 22.7\\%), MYH7 (48/542; 8.9\\%), TNNT2 (12/542; 2.2\\%), and TNNI3 (10/542; 1.8\\%). Among MYBPC3 variants, 96 led to a premature stop codon (78\\%). More surprisingly, our molecular study led also to detect, for the first time, homozygous CSRP3 truncating variants in two unrelated HCM probands. Meta-analysis of rare previously reported CSRP3 variants on HCM probands using ACMG guidelines indicate that only one variation (p.Cys58Gly) could be considered as likely pathogen. By combining meta-analysis results and identification of two unrelated HCM patients with homozygous CSRP3 truncating variants, we suggest that the association of CSRP3 as a validated HCM-causing gene require additional studies and those CSRP3 variants could result in HCM with an autosomal recessive inheritance rather than with an autosomal dominant transmission as usually reported on HCM (OMIM 612124).},\n\tlanguage = {en},\n\turldate = {2020-02-11},\n\tjournal = {Gene},\n\tauthor = {Janin, Alexandre and Bessière, Francis and Chauveau, Samuel and Chevalier, Philippe and Millat, Gilles},\n\tmonth = nov,\n\tyear = {2018},\n\tkeywords = {Bundle, CNV, CSRP3, Cardiology, Case Study, Custom Pipeline, Genomics, Hereditary Disorders, Hypertrophic Cardiomyopathy, INDEL, Illumina Sequencer, SNV, Targeted, cardiovascular disease},\n\tpages = {110--116},\n}\n\n

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\n \n\n \n \n \n \n \n \n BRCA Mutation Status to Personalize Management of Recurrent Ovarian Cancer: A Multicenter Study.\n \n \n \n \n\n\n \n Marchetti, C.; De Leo, R.; Musella, A.; D’Indinosante, M.; Capoluongo, E.; Minucci, A.; Benedetti Panici, P.; Scambia, G.; and Fagotti, A.\n\n\n \n\n\n\n Annals of Surgical Oncology, 25(12): 3701–3708. November 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"BRCA$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{marchetti_brca_2018,\n\ttitle = {{BRCA} {Mutation} {Status} to {Personalize} {Management} of {Recurrent} {Ovarian} {Cancer}: {A} {Multicenter} {Study}},\n\tvolume = {25},\n\tissn = {1534-4681},\n\tshorttitle = {{BRCA} {Mutation} {Status} to {Personalize} {Management} of {Recurrent} {Ovarian} {Cancer}},\n\turl = {https://doi.org/10.1245/s10434-018-6700-6},\n\tdoi = {10.1245/s10434-018-6700-6},\n\tabstract = {ObjectiveThe aim of this study was to assess the correlation between BRCA mutation status and disease presentation, treatment strategy, and survival in a multicenter series of recurrent high-grade serous ovarian cancer (HGSOC) women.MethodsA consecutive series of recurrent HGSOC patients with partially or fully platinum-sensitive disease admitted to the Gynecologic Oncology Units of the Catholic University of the Sacred Heart and Sapienza University of Rome. Main eligibility criteria were known BRCA 1/2 germline mutation status and a minimum follow-up period from recurrence of at least 6 months.ResultsOverall, 126 patients met the eligibility criteria, of whom 76 (60\\%) were BRCA wild-type (BRCAwt) and 50 (40\\%) were BRCA 1/2 germline mutation carriers (BRCAmut). Among the latter, 37 (74\\%) patients presented with BRCA1 mutation, and 13 (26\\%) presented with BRCA2. No differences were found regarding patterns of disease presentation between BRCAwt and BRCAmut women. BRCAmut patients had the best post-recurrence survival (PRS) regardless of having received secondary cytoreductive surgery (SCS) or not, with a 5-year PRS of 73\\% in non-resected women versus 78\\% in resected women (p = 0.558). Conversely, BRCAwt patients who underwent complete SCS had a significantly longer PRS compared with BRCAwt patients who did not receive surgery (5-year PRS of 54\\% vs. 42\\%; p = 0.048).ConclusionsRecurrent ovarian cancer BRCAmut patients have the best prognosis regardless of SCS, whereas PRS in BRCAwt women can improve when complete SCS is performed. The identification and incorporation of predictive biomarkers such as BRCA status to tailor the medical and surgical approach is paramount to the success of recurrent HGSOC treatments.},\n\tlanguage = {en},\n\tnumber = {12},\n\turldate = {2020-02-11},\n\tjournal = {Annals of Surgical Oncology},\n\tauthor = {Marchetti, Claudia and De Leo, Rossella and Musella, Angela and D’Indinosante, Marco and Capoluongo, Ettore and Minucci, Angelo and Benedetti Panici, Pierluigi and Scambia, Giovanni and Fagotti, Anna},\n\tmonth = nov,\n\tyear = {2018},\n\tkeywords = {BRCA1, BRCA1/2, BRCA2, Bundle, Clinical study, Genomics, Illumina Sequencer, Oncology, SOPHiA DDM, Solid Tumor, Targeted},\n\tpages = {3701--3708},\n}\n\n

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\n \n\n \n \n \n \n \n \n c-MET Overexpression as a Poor Predictor of MET Amplifications or Exon 14 Mutations in Lung Sarcomatoid Carcinomas.\n \n \n \n \n\n\n \n Mignard, X.; Ruppert, A.; Antoine, M.; Vasseur, J.; Girard, N.; Mazières, J.; Moro-Sibilot, D.; Fallet, V.; Rabbe, N.; Thivolet-Bejui, F.; Rouquette, I.; Lantuejoul, S.; Cortot, A.; Saffroy, R.; Cadranel, J.; Lemoine, A.; and Wislez, M.\n\n\n \n\n\n\n Journal of Thoracic Oncology, 13(12): 1962–1967. December 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"c-MET$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{mignard_c-met_2018,\n\ttitle = {c-{MET} {Overexpression} as a {Poor} {Predictor} of {MET} {Amplifications} or {Exon} 14 {Mutations} in {Lung} {Sarcomatoid} {Carcinomas}},\n\tvolume = {13},\n\tissn = {1556-0864},\n\turl = {http://www.sciencedirect.com/science/article/pii/S1556086418309663},\n\tdoi = {10.1016/j.jtho.2018.08.008},\n\tabstract = {Introduction\nMNNG HOS transforming gene (MET) abnormalities such as amplification and exon 14 mutations may be responsive to targeted therapies. They are prevalent in lung sarcomatoid carcinomas (LSCs) and must be diagnosed as efficiently as possible. Hypothetically, c-MET overexpression by immunohistochemistry (IHC) may prove effective as a screening test for MET abnormalities.\nMethods\nTissue samples were obtained from consecutive patients with a resected LSC in four oncologic centers. IHC was performed using the SP44 antibody (Ventana, Tucson, Arizona) and evaluated using the MetMab score and H-score. Fluorescence in situ hybridization was applied with the dual color probe set from Zytovision (Clinisciences, Nanterre, France). True MET amplification was diagnosed when MET gene copy number was 5 or greater and the ratio between MET gene copy number and chromosome 7 number was greater than 2. All MET exon 14 alterations including those affecting splice sites occurring within splice donor and acceptor sites were detected in the routine molecular testing on genetic platforms.\nResults\nA total of 81 LSCs were included. Fourteen (17\\%) exhibited positive IHC using the MetMab score and 15 (18.5\\%) using the H-score. MET amplification was detected in six tumors (8.5\\%) and MET exon 14 mutation in five (6\\%). A weak positive correlation between IHC and fluorescence in situ hybridization was found (r = 0.27, p = 0.0001). IHC sensitivity for MET amplification was 50\\%, with a specificity of 83\\%, positive predictive value of 21.4\\%, and negative predictive value of 94.7\\%. IHC sensitivity for MET exon 14 mutations was 20\\%, with a specificity of 83\\%, positive predictive value of 7\\%, and negative predictive value of 94\\%.\nConclusion\nIHC is not a relevant screening tool for MET abnormalities in LSC.},\n\tlanguage = {en},\n\tnumber = {12},\n\turldate = {2020-02-11},\n\tjournal = {Journal of Thoracic Oncology},\n\tauthor = {Mignard, Xavier and Ruppert, Anne-Marie and Antoine, Martine and Vasseur, Julie and Girard, Nicolas and Mazières, Julien and Moro-Sibilot, Denis and Fallet, Vincent and Rabbe, Nathalie and Thivolet-Bejui, Françoise and Rouquette, Isabelle and Lantuejoul, Sylvie and Cortot, Alexis and Saffroy, Raphaël and Cadranel, Jacques and Lemoine, Antoinette and Wislez, Marie},\n\tmonth = dec,\n\tyear = {2018},\n\tkeywords = {Commercial, Genomics, INDEL, MET, NSCLC, Oncology, STS, Solid Tumor},\n\tpages = {1962--1967},\n}\n\n

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\n \n\n \n \n \n \n \n \n Unravelling the pathogenic role and genotype-phenotype correlation of the USH2A p.(Cys759Phe) variant among Spanish families.\n \n \n \n \n\n\n \n Pérez-Carro, R.; Blanco-Kelly, F.; Galbis-Martínez, L.; García-García, G.; Aller, E.; García-Sandoval, B.; Mínguez, P.; Corton, M.; Mahíllo-Fernández, I.; Martín-Mérida, I.; Avila-Fernández, A.; Millán, J. M.; and Ayuso, C.\n\n\n \n\n\n\n PLoS ONE, 13(6). June 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"Unravelling$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{perez-carro_unravelling_2018,\n\ttitle = {Unravelling the pathogenic role and genotype-phenotype correlation of the {USH2A} p.({Cys759Phe}) variant among {Spanish} families},\n\tvolume = {13},\n\tissn = {1932-6203},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005481/},\n\tdoi = {10.1371/journal.pone.0199048},\n\tnumber = {6},\n\turldate = {2020-02-11},\n\tjournal = {PLoS ONE},\n\tauthor = {Pérez-Carro, Raquel and Blanco-Kelly, Fiona and Galbis-Martínez, Lilián and García-García, Gema and Aller, Elena and García-Sandoval, Blanca and Mínguez, Pablo and Corton, Marta and Mahíllo-Fernández, Ignacio and Martín-Mérida, Inmaculada and Avila-Fernández, Almudena and Millán, José M. and Ayuso, Carmen},\n\tmonth = jun,\n\tyear = {2018},\n\tpmid = {29912909},\n\tpmcid = {PMC6005481},\n\tkeywords = {Blood, CES, CNV, Clinical study, Exome, Genomics, Hereditary Disorders, SOPHiA DDM, USH2A},\n}\n\n

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\n \n\n \n \n \n \n \n \n Multicenter validation study for the certification of a CFTR gene scanning method using next generation sequencing technology.\n \n \n \n \n\n\n \n Bergougnoux, A.; D’Argenio, V.; Sollfrank, S.; Verneau, F.; Telese, A.; Postiglione, I.; Lackner, K. J.; Claustres, M.; Castaldo, G.; Rossmann, H.; Salvatore, F.; and Raynal, C.\n\n\n \n\n\n\n Clinical Chemistry and Laboratory Medicine (CCLM), 56(7): 1046–1053. February 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"Multicenter$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{bergougnoux_multicenter_2018,\n\ttitle = {Multicenter validation study for the certification of a {CFTR} gene scanning method using next generation sequencing technology},\n\tvolume = {56},\n\tissn = {1434-6621},\n\turl = {https://www.degruyter.com/view/j/cclm.2018.56.issue-7/cclm-2017-0553/cclm-2017-0553.xml},\n\tdoi = {10.1515/cclm-2017-0553},\n\tnumber = {7},\n\turldate = {2020-02-11},\n\tjournal = {Clinical Chemistry and Laboratory Medicine (CCLM)},\n\tauthor = {Bergougnoux, Anne and D’Argenio, Valeria and Sollfrank, Stefanie and Verneau, Fanny and Telese, Antonella and Postiglione, Irene and Lackner, Karl J. and Claustres, Mireille and Castaldo, Giuseppe and Rossmann, Heidi and Salvatore, Francesco and Raynal, Caroline},\n\tmonth = feb,\n\tyear = {2018},\n\tkeywords = {Benchmark, Blood, CE-IVD, CF, CFTR, CFTR-RDs, CFTR-Related Disorders, CNV, Case Study, Cystic Fibrosis, Genomics, Hereditary Disorders, INDEL, Illumina Sequencer, SOPHiA DDM, Targeted},\n\tpages = {1046--1053},\n}\n\n

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\n \n\n \n \n \n \n \n \n A reliable targeted next-generation sequencing strategy for diagnosis of myopathies and muscular dystrophies, especially for the giant titin and nebulin genes.\n \n \n \n \n\n\n \n Zenagui, R.; Lacourt, D.; Pegeot, H.; Yauy, K.; Morales, R. J.; Theze, C.; Rivier, F.; Cances, C.; Sole, G.; and Renard, D.\n\n\n \n\n\n\n The Journal of Molecular Diagnostics, 20(4): 533–549. July 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{zenagui_reliable_2018,\n\ttitle = {A reliable targeted next-generation sequencing strategy for diagnosis of myopathies and muscular dystrophies, especially for the giant titin and nebulin genes},\n\tvolume = {20},\n\turl = {https://www.sciencedirect.com/science/article/pii/S1525157817303185},\n\tnumber = {4},\n\tjournal = {The Journal of Molecular Diagnostics},\n\tauthor = {Zenagui, Reda and Lacourt, Delphine and Pegeot, Henri and Yauy, Kevin and Morales, Raul Juntas and Theze, Corine and Rivier, François and Cances, Claude and Sole, Guilhem and Renard, Dimitri},\n\tmonth = jul,\n\tyear = {2018},\n\tkeywords = {Blood, Bundle, CNV, Custom, Exome, Familial Segregation, Genomics, Hereditary Disorders, INDEL, Illumina Sequencer, Large panel, Liquid Biopsy, NEB, SNV, SOPHiA DDM, TTN, Targeted},\n\tpages = {533--549},\n}\n\n

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\n \n\n \n \n \n \n \n \n Germline loss-of-function variants in the BARD1 gene are associated with familial breast cancer.\n \n \n \n \n\n\n \n Weber-Lassalle, N.; Borde, J.; Weber-Lassalle, K.; Klaschik, K.; Neidhardt, G.; Ernst, C.; Blümcke, B.; Klonowska, K.; Volk, A.; and Kubisch, C.\n\n\n \n\n\n\n Senologie-Zeitschrift für Mammadiagnostik und-therapie, 15(02): 148. May 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"Germline$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{weber-lassalle_germline_2018,\n\ttitle = {Germline loss-of-function variants in the {BARD1} gene are associated with familial breast cancer},\n\tvolume = {15},\n\turl = {https://www.thieme-connect.com/products/ejournals/html/10.1055/s-0038-1651818},\n\tnumber = {02},\n\tjournal = {Senologie-Zeitschrift für Mammadiagnostik und-therapie},\n\tauthor = {Weber-Lassalle, N. and Borde, J. and Weber-Lassalle, K. and Klaschik, K. and Neidhardt, G. and Ernst, C. and Blümcke, B. and Klonowska, K. and Volk, A. and Kubisch, C.},\n\tmonth = may,\n\tyear = {2018},\n\tkeywords = {Abstract, BARD1, CNV, Cancer, Familial Breast Cancer, Genomics, Hereditary Disorders, LoF, Loss-of-Function, SOPHiA DDM},\n\tpages = {148},\n}\n\n

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\n \n\n \n \n \n \n \n \n PO-398 Benchmarkingof amplicon-based next-generation sequencing panels combined with bioinformatics solutions for BRCA1 and BRCA2 alteration detection.\n \n \n \n \n\n\n \n Vilquin, P.; Vendrell, J.; Larrieux, M.; Van Goethem, C.; and Solassol, J.\n\n\n \n\n\n\n BMJ Publishing Group Limited, June 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"PO-398$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@book{vilquin_po-398_2018,\n\ttitle = {{PO}-398 {Benchmarkingof} amplicon-based next-generation sequencing panels combined with bioinformatics solutions for {BRCA1} and {BRCA2} alteration detection},\n\turl = {https://esmoopen.bmj.com/content/esmoopen/3/Suppl_2/A178.2.full.pdf},\n\tpublisher = {BMJ Publishing Group Limited},\n\tauthor = {Vilquin, P. and Vendrell, J. and Larrieux, M. and Van Goethem, C. and Solassol, J.},\n\tmonth = jun,\n\tyear = {2018},\n\tkeywords = {Benchmark, Bundle, Genomics, Oncology, SOPHiA DDM, Solid Tumor, Targeted},\n}\n\n

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\n \n\n \n \n \n \n \n \n Differential expression of PD-L1 and immune biomarkers by age: Decreased expression in pediatric/AYA patients with advanced cancer.\n \n \n \n \n\n\n \n Hamid, O.; Vanderwalde, A. M.; Szeto, C.; Reddy, S.; and Pal, S. K.\n\n\n \n\n\n\n Annals of Oncology, 29: viii32. October 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"Differential$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{hamid_differential_2018,\n\ttitle = {Differential expression of {PD}-{L1} and immune biomarkers by age: {Decreased} expression in pediatric/{AYA} patients with advanced cancer},\n\tvolume = {29},\n\tissn = {0923-7534, 1569-8041},\n\tshorttitle = {Differential expression of {PD}-{L1} and immune biomarkers by age},\n\turl = {https://www.annalsofoncology.org/article/S0923-7534(19)48527-X/abstract},\n\tdoi = {10.1093/annonc/mdy269.099},\n\tabstract = {Background: The activity of immune checkpoint inhibitors (ICIs) varies substantially\nat the extremes of age. We interrogated our tissue database (n=1,467) to determine\nif expression of checkpoint molecules or variations in tumor mutational burden (TMB)\ncould explain this phenomenon.},\n\tlanguage = {English},\n\turldate = {2020-02-11},\n\tjournal = {Annals of Oncology},\n\tauthor = {Hamid, O. and Vanderwalde, A. M. and Szeto, C. and Reddy, S. and Pal, S. K.},\n\tmonth = oct,\n\tyear = {2018},\n\tkeywords = {Abstract, Blood, Genomics, Liquid Biopsy, Solid Tumor, cfDNA},\n\tpages = {viii32},\n}\n\n

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\n \n\n \n \n \n \n \n \n Frequency of Rearrangements Versus Small Indels Mutations in BRCA1 and BRCA2 Genes in Turkish Patients with High Risk Breast and Ovarian Cancer.\n \n \n \n \n\n\n \n Yazıcı, H.; Kılıç, S.; Akdeniz, D.; Şükrüoğlu, Ö.; Tuncer, Ş. B.; Avşar, M.; Kuru, G.; Çelik, B.; Küçücük, S.; and Saip, P.\n\n\n \n\n\n\n European Journal of Breast Health, 14(2): 93–99. April 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"Frequency$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{yazici_frequency_2018,\n\ttitle = {Frequency of {Rearrangements} {Versus} {Small} {Indels} {Mutations} in {BRCA1} and {BRCA2} {Genes} in {Turkish} {Patients} with {High} {Risk} {Breast} and {Ovarian} {Cancer}},\n\tvolume = {14},\n\tissn = {2587-0831},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5939985/},\n\tdoi = {10.5152/ejbh.2017.3799},\n\tnumber = {2},\n\turldate = {2020-02-11},\n\tjournal = {European Journal of Breast Health},\n\tauthor = {Yazıcı, Hülya and Kılıç, Seda and Akdeniz, Demet and Şükrüoğlu, Özge and Tuncer, Şeref Buğra and Avşar, Mukaddes and Kuru, Gözde and Çelik, Betül and Küçücük, Seden and Saip, Pınar},\n\tmonth = apr,\n\tyear = {2018},\n\tpmid = {29774317},\n\tpmcid = {PMC5939985},\n\tkeywords = {Alamut, Genomics, Hereditary Disorders, MLPA, Rearrangements, Targeted},\n\tpages = {93--99},\n}\n\n

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\n \n\n \n \n \n \n \n \n Trio clinical exome sequencing in a patient with multicentric carpotarsal osteolysis syndrome: first case report in the Balkans.\n \n \n \n \n\n\n \n Stajkovska, A.; Mehandziska, S.; Stavrevska, M.; Jakovleva, K.; Nikchevska, N.; Mitrev, Z.; Kungulovski, I.; Zafiroski, G.; Tasic, V.; and Kungulovski, G.\n\n\n \n\n\n\n Frontiers in Genetics, 9: 113. April 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"Trio$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{stajkovska_trio_2018,\n\ttitle = {Trio clinical exome sequencing in a patient with multicentric carpotarsal osteolysis syndrome: first case report in the {Balkans}},\n\tvolume = {9},\n\tshorttitle = {Trio clinical exome sequencing in a patient with multicentric carpotarsal osteolysis syndrome},\n\turl = {https://www.frontiersin.org/articles/10.3389/fgene.2018.00113/full?report=reader},\n\tjournal = {Frontiers in Genetics},\n\tauthor = {Stajkovska, Aleksandra and Mehandziska, Sanja and Stavrevska, Margarita and Jakovleva, Kristina and Nikchevska, Natasha and Mitrev, Zan and Kungulovski, Ivan and Zafiroski, Gjorgje and Tasic, Velibor and Kungulovski, Goran},\n\tmonth = apr,\n\tyear = {2018},\n\tkeywords = {CES, Case Study, Exome, Genomics, SOPHiA DDM, Trio analysis},\n\tpages = {113},\n}\n\n

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\n \n\n \n \n \n \n \n \n Autosomal Recessive Trait of UMOD Gene in Consanguineous Family Presented with End Stage Renal Disease.\n \n \n \n \n\n\n \n Yildiz, A.; Gorukmez, O.; Oruc, A.; Gul, C. B.; Akgur, S.; Unsal, O.; Aydin, M. F.; and Ersoy, A.\n\n\n \n\n\n\n Journal of Clinical & Experimental Nephrology, 3(4). December 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"Autosomal$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{yildiz_autosomal_2018,\n\ttitle = {Autosomal {Recessive} {Trait} of {UMOD} {Gene} in {Consanguineous} {Family} {Presented} with {End} {Stage} {Renal} {Disease}},\n\tvolume = {3},\n\tissn = {ISSN No. 2472-5056},\n\turl = {http://clinical-experimental-nephrology.imedpub.com/abstract/autosomal-recessive-trait-of-umod-gene-in-consanguineous-family-presented-with-end-stage-renal-disease-24040.html},\n\tdoi = {10.21767/2472-5056.100072},\n\tlanguage = {en},\n\tnumber = {4},\n\turldate = {2020-02-11},\n\tjournal = {Journal of Clinical \\& Experimental Nephrology},\n\tauthor = {Yildiz, Abdulmecit and Gorukmez, Orhan and Oruc, Aysegul and Gul, Cuma Bulent and Akgur, Suat and Unsal, Oktay and Aydin, M. Fethullah and Ersoy, Alparslan},\n\tmonth = dec,\n\tyear = {2018},\n}\n\n

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\n \n\n \n \n \n \n \n \n 102PPotential resistance mechanisms revealed primary resistance to crizotinib in ROS1+ non-small cell lung cancer using next generation sequencing: A multicenter study.\n \n \n \n \n\n\n \n Zhang, Q; Xu, C; Wang, W; Zhuang, W; Song, Z; Zhu, Y; Chen, Y; Chen, G; Fang, M; Lv, T; and Song, Y\n\n\n \n\n\n\n Annals of Oncology, 29(suppl_8). October 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"102PPotential$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{zhang_102ppotential_2018,\n\ttitle = {{102PPotential} resistance mechanisms revealed primary resistance to crizotinib in {ROS1}+ non-small cell lung cancer using next generation sequencing: {A} multicenter study},\n\tvolume = {29},\n\tissn = {0923-7534, 1569-8041},\n\tshorttitle = {{102PPotential} resistance mechanisms revealed primary resistance to crizotinib in {ROS1}+ non-small cell lung cancer using next generation sequencing},\n\turl = {https://academic.oup.com/annonc/article/doi/10.1093/annonc/mdy269.100/5141183},\n\tdoi = {10.1093/annonc/mdy269.100},\n\tlanguage = {en},\n\tnumber = {suppl\\_8},\n\turldate = {2020-02-11},\n\tjournal = {Annals of Oncology},\n\tauthor = {Zhang, Q and Xu, C and Wang, W and Zhuang, W and Song, Z and Zhu, Y and Chen, Y and Chen, G and Fang, M and Lv, T and Song, Y},\n\tmonth = oct,\n\tyear = {2018},\n}\n\n

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\n \n\n \n \n \n \n \n \n The association of endothelin-1 levels with renal survival in polycystic kidney disease patients.\n \n \n \n \n\n\n \n Kocyigit, I.; Eroglu, E.; Kaynar, A. S.; Kocer, D.; Kargi, S.; Zararsiz, G.; Bayramov, R.; Imamoglu, H.; Sipahioglu, M. H.; and Tokgoz, B.\n\n\n \n\n\n\n Journal of nephrology, 32(1): 83–91. July 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"The$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{kocyigit_association_2018,\n\ttitle = {The association of endothelin-1 levels with renal survival in polycystic kidney disease patients},\n\tvolume = {32},\n\turl = {https://link.springer.com/article/10.1007/s40620-018-0514-2},\n\tnumber = {1},\n\tjournal = {Journal of nephrology},\n\tauthor = {Kocyigit, Ismail and Eroglu, Eray and Kaynar, Ahmet Safa and Kocer, Derya and Kargi, Seval and Zararsiz, Gokmen and Bayramov, Ruslan and Imamoglu, Hakan and Sipahioglu, Murat Hayri and Tokgoz, Bulent},\n\tmonth = jul,\n\tyear = {2018},\n\tkeywords = {Custom, Genomic Hereditary Disorders, Illumina Sequencer, Liquid Biopsy, SOPHiA DDM, Targeted},\n\tpages = {83--91},\n}\n\n

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\n \n\n \n \n \n \n \n \n PO-399 Genome wide histone modification patterns at the promoter regions are distinct in low and high grade gliomas.\n \n \n \n \n\n\n \n Stepniak, K.; Mieczkowski, J.; Macioszek, A.; Wojtas, B.; Gielniewski, B.; Czernicki, T.; Grajkowska, W.; Kotulska, K.; Wilczynski, B.; and Kaminska, B.\n\n\n \n\n\n\n BMJ Publishing Group Limited, June 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"PO-399$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@book{stepniak_po-399_2018,\n\ttitle = {{PO}-399 {Genome} wide histone modification patterns at the promoter regions are distinct in low and high grade gliomas},\n\turl = {https://esmoopen.bmj.com/content/esmoopen/3/Suppl_2/A179.1.full.pdf},\n\tpublisher = {BMJ Publishing Group Limited},\n\tauthor = {Stepniak, K. and Mieczkowski, J. and Macioszek, A. and Wojtas, B. and Gielniewski, B. and Czernicki, T. and Grajkowska, W. and Kotulska, K. and Wilczynski, B. and Kaminska, B.},\n\tmonth = jun,\n\tyear = {2018},\n}\n\n

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\n \n\n \n \n \n \n \n \n PO-401 Detection of mutational patterns associated to HR deficiency from low counts of mutations.\n \n \n \n \n\n\n \n Gulhan, D.; Park, P.; Lee, J. K. J.; and Melloni, G.\n\n\n \n\n\n\n BMJ Publishing Group Limited, June 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"PO-401$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@book{gulhan_po-401_2018,\n\ttitle = {{PO}-401 {Detection} of mutational patterns associated to {HR} deficiency from low counts of mutations},\n\turl = {https://esmoopen.bmj.com/content/esmoopen/3/Suppl_2/A179.3.full.pdf},\n\tpublisher = {BMJ Publishing Group Limited},\n\tauthor = {Gulhan, D. and Park, P. and Lee, J. K. J. and Melloni, G.},\n\tmonth = jun,\n\tyear = {2018},\n}\n\n

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\n \n\n \n \n \n \n \n \n PO-395 Mechanistic investigation of epigenetic modifications induced by metabolic changes in AML.\n \n \n \n \n\n\n \n Donato, E.; Raffel, S.; Falcone, M.; Herrmann, C.; and Trumpp, A.\n\n\n \n\n\n\n BMJ Publishing Group Limited, June 2018.\n \n\n\n\n
\n\n\n\n \n \n $\"PO-395$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@book{donato_po-395_2018,\n\ttitle = {{PO}-395 {Mechanistic} investigation of epigenetic modifications induced by metabolic changes in {AML}},\n\turl = {https://esmoopen.bmj.com/content/esmoopen/3/Suppl_2/A177.2.full.pdf},\n\tpublisher = {BMJ Publishing Group Limited},\n\tauthor = {Donato, E. and Raffel, S. and Falcone, M. and Herrmann, C. and Trumpp, A.},\n\tmonth = jun,\n\tyear = {2018},\n}\n\n

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\n \n 2017\n \n \n (13)\n \n \n

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\n \n\n \n \n \n \n \n \n Truncating mutations on myofibrillar myopathies causing genes as prevalent molecular explanations on patients with dilated cardiomyopathy.\n \n \n \n \n\n\n \n Janin, A.; N'Guyen, K.; Habib, G.; Dauphin, C.; Chanavat, V.; Bouvagnet, P.; Eschalier, R.; Streichenberger, N.; Chevalier, P.; and Millat, G.\n\n\n \n\n\n\n Clinical Genetics, 92(6): 616–623. April 2017.\n _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/cge.13043\n\n\n\n
\n\n\n\n \n \n $\"Truncating$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{janin_truncating_2017,\n\ttitle = {Truncating mutations on myofibrillar myopathies causing genes as prevalent molecular explanations on patients with dilated cardiomyopathy},\n\tvolume = {92},\n\tcopyright = {© 2017 John Wiley \\& Sons A/S. Published by John Wiley \\& Sons Ltd},\n\tissn = {1399-0004},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1111/cge.13043},\n\tdoi = {https://doi.org/10.1111/cge.13043},\n\tabstract = {Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure with high morbidity and mortality. More than 40 genes have been reported to cause DCM. To provide new insights into the pathophysiology of dilated cardiomyopathy, a next-generation sequencing (NGS) workflow based on a panel of 48 cardiomyopathies-causing genes was used to analyze a cohort of 222 DCM patients. Truncating variants were detected on 63 unrelated DCM cases (28.4\\%). Most of them were identified, as expected, on TTN (29 DCM probands), but truncating variants were also identified on myofibrillar myopathies causing genes in 17 DCM patients (7.7\\% of the DCM cohort): 10 variations on FLNC and 7 variations on BAG3 . This study confirms that truncating variants on myofibrillar myopathies causing genes are frequently associated with dilated cardiomyopathies and also suggest that FLNC mutations could be considered as a common cause of dilated cardiomyopathy. Molecular approaches that would allow to detect systematically truncating variants in FLNC and BAG3 into genetic testing should significantly increase test sensitivity, thereby allowing earlier diagnosis and therapeutic intervention for many patients with dilated cardiomyopathy.},\n\tlanguage = {en},\n\tnumber = {6},\n\turldate = {2021-03-23},\n\tjournal = {Clinical Genetics},\n\tauthor = {Janin, A. and N'Guyen, K. and Habib, G. and Dauphin, C. and Chanavat, V. and Bouvagnet, P. and Eschalier, R. and Streichenberger, N. and Chevalier, P. and Millat, G.},\n\tmonth = apr,\n\tyear = {2017},\n\tnote = {\\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/cge.13043},\n\tkeywords = {SOPHiA DDM, arrhythmia, dilated cardiomyopathy, filamin C, molecular diagnosis, sudden death},\n\tpages = {616--623},\n}\n\n

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\n \n\n \n \n \n \n \n \n Technical insights into highly sensitive isolation and molecular characterization of fixed and live circulating tumor cells for early detection of tumor invasion.\n \n \n \n \n\n\n \n Laget, S.; Broncy, L.; Hormigos, K.; Dhingra, D. M.; BenMohamed, F.; Capiod, T.; Osteras, M.; Farinelli, L.; Jackson, S.; and Paterlini-Brechot, P.\n\n\n \n\n\n\n PloS one, 12(1). January 2017.\n \n\n\n\n
\n\n\n\n \n \n $\"Technical$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{laget_technical_2017,\n\ttitle = {Technical insights into highly sensitive isolation and molecular characterization of fixed and live circulating tumor cells for early detection of tumor invasion},\n\tvolume = {12},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5218415/},\n\tnumber = {1},\n\tjournal = {PloS one},\n\tauthor = {Laget, Sophie and Broncy, Lucile and Hormigos, Katia and Dhingra, Dalia M. and BenMohamed, Fatima and Capiod, Thierry and Osteras, Magne and Farinelli, Laurent and Jackson, Stephen and Paterlini-Brechot, Patrizia},\n\tmonth = jan,\n\tyear = {2017},\n\tkeywords = {Blood, CTC, Cancer, Genomics, INDEL, SNV, SOPHiA DDM},\n}\n\n

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\n \n\n \n \n \n \n \n \n Testing of BRCA 1/2 gene mutations in FFPE samples of patients with high-grade serous ovarian cancer and limits of its bioinformatic interpretation.\n \n \n \n \n\n\n \n Janikova, K.; Lasabova, Z.; Grendar, M.; Farkasova, A.; Scheerova, K.; Slavik, P.; Vanova, B.; Zelinova, K.; Jagelkova, M.; and Plank, L.\n\n\n \n\n\n\n American Society of Clinical Oncology, May 2017.\n \n\n\n\n
\n\n\n\n \n \n $\"Testing$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@book{janikova_testing_2017,\n\ttitle = {Testing of {BRCA} 1/2 gene mutations in {FFPE} samples of patients with high-grade serous ovarian cancer and limits of its bioinformatic interpretation.},\n\turl = {https://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.e17060},\n\tpublisher = {American Society of Clinical Oncology},\n\tauthor = {Janikova, Katarina and Lasabova, Zora and Grendar, Marian and Farkasova, Anna and Scheerova, Karla and Slavik, Pavol and Vanova, Barbora and Zelinova, Katarina and Jagelkova, Marianna and Plank, Lukas},\n\tmonth = may,\n\tyear = {2017},\n\tkeywords = {Abstract, BRCA1, BRCA1/2, BRCA2, FFPE, Genomics, High-Grade Serous Ovarian Cancer, Ovarian Cancer, SOPHiA DDM, Solid Tumor, Targeted},\n}\n\n

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\n \n\n \n \n \n \n \n \n An evaluation of the challenges to developing tumor BRCA1 and BRCA2 testing methodologies for clinical practice.\n \n \n \n \n\n\n \n Ellison, G.; Ahdesmäki, M.; Luke, S.; Waring, P. M.; Wallace, A.; Wright, R.; Röthlisberger, B.; Ludin, K.; Merkelbach‐Bruse, S.; Heydt, C.; Ligtenberg, M. J. L.; Mensenkamp, A. R.; Castro, D. G. d.; Jones, T.; Vivancos, A.; Kondrashova, O.; Pauwels, P.; Weyn, C.; Hahnen, E.; Hauke, J.; Soong, R.; Lai, Z.; Dougherty, B.; Carr, T. H.; Johnson, J.; Mills, J.; and Barrett, J. C.\n\n\n \n\n\n\n Human Mutation, 39(3): 394–405. December 2017.\n \n\n\n\n
\n\n\n\n \n \n $\"An$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{ellison_evaluation_2017,\n\ttitle = {An evaluation of the challenges to developing tumor {BRCA1} and {BRCA2} testing methodologies for clinical practice},\n\tvolume = {39},\n\tcopyright = {© 2017 The Authors. Human Mutation published by Wiley Periodicals, Inc.},\n\tissn = {1098-1004},\n\turl = {https://onlinelibrary.wiley.com/doi/abs/10.1002/humu.23375},\n\tdoi = {10.1002/humu.23375},\n\tabstract = {Ovarian cancer patients with germline or somatic pathogenic variants benefit from treatment with poly ADP ribose polymerase (PARP) inhibitors. Tumor BRCA1/2 testing is more challenging than germline testing as the majority of samples are formalin-fixed paraffin embedded (FFPE), the tumor genome is complex, and the allelic fraction of somatic variants can be low. We collaborated with 10 laboratories testing BRCA1/2 in tumors to compare different approaches to identify clinically important variants within FFPE tumor DNA samples. This was not a proficiency study but an inter-laboratory comparison to identify common issues. Each laboratory received the same tumor DNA samples ranging in genotype, quantity, quality, and variant allele frequency (VAF). Each laboratory performed their preferred next-generation sequencing method to report on the variants. No false positive results were reported in this small study and the majority of methods detected the low VAF variants. A number of variants were not detected due to the bioinformatics analysis, variant classification, or insufficient DNA. The use of hybridization capture or short amplicon methods are recommended based on a bioinformatic assessment of the data. The study highlights the importance of establishing standards and standardization for tBRCA testing particularly when the test results dictate clinical decisions regarding life extending therapies.},\n\tlanguage = {en},\n\tnumber = {3},\n\turldate = {2020-02-11},\n\tjournal = {Human Mutation},\n\tauthor = {Ellison, Gillian and Ahdesmäki, Miika and Luke, Sally and Waring, Paul M. and Wallace, Andrew and Wright, Ronnie and Röthlisberger, Benno and Ludin, Katja and Merkelbach‐Bruse, Sabine and Heydt, Carina and Ligtenberg, Marjolijn J. L. and Mensenkamp, Arjen R. and Castro, David Gonzalez de and Jones, Thomas and Vivancos, Ana and Kondrashova, Olga and Pauwels, Patrick and Weyn, Christine and Hahnen, Eric and Hauke, Jan and Soong, Richie and Lai, Zhongwu and Dougherty, Brian and Carr, T. Hedley and Johnson, Justin and Mills, John and Barrett, J. Carl},\n\tmonth = dec,\n\tyear = {2017},\n\tkeywords = {Alu, Ampulla of Vater Carcinomas, BRCA1, BRCA1/2, BRCA2, Blood, Breast cancer, Clinical study, FFPE, Genomics, Ovarian Cancer, Solid Tumor},\n\tpages = {394--405},\n}\n\n

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\n \n\n \n \n \n \n \n \n MET exon 14 mutations as targets in routine molecular analysis of primary sarcomatoid carcinoma of the lung.\n \n \n \n \n\n\n \n Saffroy, R.; Fallet, V.; Girard, N.; Mazieres, J.; Sibilot, D. M.; Lantuejoul, S.; Rouquette, I.; Thivolet-Bejui, F.; Vieira, T.; Antoine, M.; Cadranel, J.; Lemoine, A.; and Wislez, M.\n\n\n \n\n\n\n Oncotarget, 8(26): 42428–42437. March 2017.\n \n\n\n\n
\n\n\n\n \n \n $\"MET$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{saffroy_met_2017,\n\ttitle = {{MET} exon 14 mutations as targets in routine molecular analysis of primary sarcomatoid carcinoma of the lung},\n\tvolume = {8},\n\tissn = {1949-2553},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522077/},\n\tdoi = {10.18632/oncotarget.16403},\n\tabstract = {MET exon 14 splicing mutations are new targetable oncogenic drivers reported in 3\\% of non-small cell lung cancer (NSCLC) cases and have been shown to be more common in pulmonary sarcomatoid carcinomas (PSCs). This study sought to screen mutations affecting MET exon 14 splice sites in a large SC cohort of Caucasian patients, with a large adenocarcinoma cohort as internal control., We tested 81 patients with SC and 150 with adenocarcinoma for splice site DNA mutations leading to RNA splicing-based skipping of MET exon 14. To this end, we employed a mass spectrometry-based custom-designed PCR assay for routine analysis of whole MET exon 14 and flanking intronic regions using formalin-fixed paraffin-embedded (FFPE) tumor samples., Our results revealed a 4.9\\% mutation rate for MET exon 14 mutations in Caucasian SC patients, which is, though highly variable, within the usual range reported in NSCLC. Discrepancies with previous results reported in SC could be accounted for the small number of cases, ethnicity, epithelial component, and percentage of other driver mutations, such as KRAS, in the patient populations studied. Based on our study findings, SC patients should be screened for MET exon 14 mutations in the same manner as adenocarcinoma patients.},\n\tnumber = {26},\n\turldate = {2020-02-11},\n\tjournal = {Oncotarget},\n\tauthor = {Saffroy, Raphaël and Fallet, Vincent and Girard, Nicolas and Mazieres, Julien and Sibilot, Denis Moro and Lantuejoul, Sylvie and Rouquette, Isabelle and Thivolet-Bejui, Françoise and Vieira, Thibaut and Antoine, Martine and Cadranel, Jacques and Lemoine, Antoinette and Wislez, Marie},\n\tmonth = mar,\n\tyear = {2017},\n\tpmid = {28418914},\n\tpmcid = {PMC5522077},\n\tkeywords = {Benchmark, Bundle, FFPE, Genomics, INDEL, Illumina Sequencer, NSCLC, Non-Small Cell Lung Cancer, Oncology, PSCs, Pulmonary Sarcomatoid Carcinomas, SOPHiA DDM, STS, Solid Tumor, Targeted, Thermo Fischer Sequencer},\n\tpages = {42428--42437},\n}\n\n

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\n \n\n \n \n \n \n \n \n Detection of BRCA1/2 mutations in circulating tumor DNA from patients with ovarian cancer.\n \n \n \n \n\n\n \n Ratajska, M.; Koczkowska, M.; Żuk, M.; Gorczyński, A.; Kuźniacka, A.; Stukan, M.; Biernat, W.; Limon, J.; and Wasąg, B.\n\n\n \n\n\n\n Oncotarget, 8(60): 101325–101332. September 2017.\n \n\n\n\n
\n\n\n\n \n \n $\"Detection$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{ratajska_detection_2017,\n\ttitle = {Detection of {BRCA1}/2 mutations in circulating tumor {DNA} from patients with ovarian cancer},\n\tvolume = {8},\n\tissn = {1949-2553},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731877/},\n\tdoi = {10.18632/oncotarget.20722},\n\tnumber = {60},\n\turldate = {2020-02-11},\n\tjournal = {Oncotarget},\n\tauthor = {Ratajska, Magdalena and Koczkowska, Magdalena and Żuk, Monika and Gorczyński, Adam and Kuźniacka, Alina and Stukan, Maciej and Biernat, Wojciech and Limon, Janusz and Wasąg, Bartosz},\n\tmonth = sep,\n\tyear = {2017},\n\tpmid = {29254167},\n\tpmcid = {PMC5731877},\n\tkeywords = {Alamut, BRCA1, BRCA1/2, BRCA2, Blood, Clinical Trials, Clinical study, Genomics, Hereditary Disorders, Liquid Biopsy, Ovarian Cancer, PARP1 inhibitors, SOPHiA DDM, ctDNA},\n\tpages = {101325--101332},\n}\n\n

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\n \n\n \n \n \n \n \n \n Prevalence of deleterious germline variants in risk genes including BRCA1/2 in consecutive ovarian cancer patients (AGO-TR-1).\n \n \n \n \n\n\n \n Harter, P.; Hauke, J.; Heitz, F.; Reuss, A.; Kommoss, S.; Marmé, F.; Heimbach, A.; Prieske, K.; Richters, L.; Burges, A.; Neidhardt, G.; de Gregorio, N.; El-Balat, A.; Hilpert, F.; Meier, W.; Kimmig, R.; Kast, K.; Sehouli, J.; Baumann, K.; Jackisch, C.; Park-Simon, T.; Hanker, L.; Kröber, S.; Pfisterer, J.; Gevensleben, H.; Schnelzer, A.; Dietrich, D.; Neunhöffer, T.; Krockenberger, M.; Brucker, S. Y.; Nürnberg, P.; Thiele, H.; Altmüller, J.; Lamla, J.; Elser, G.; du Bois, A.; Hahnen, E.; and Schmutzler, R.\n\n\n \n\n\n\n PLoS ONE, 12(10). October 2017.\n \n\n\n\n
\n\n\n\n \n \n $\"Prevalence$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{harter_prevalence_2017,\n\ttitle = {Prevalence of deleterious germline variants in risk genes including {BRCA1}/2 in consecutive ovarian cancer patients ({AGO}-{TR}-1)},\n\tvolume = {12},\n\tissn = {1932-6203},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650145/},\n\tdoi = {10.1371/journal.pone.0186043},\n\tnumber = {10},\n\turldate = {2020-02-11},\n\tjournal = {PLoS ONE},\n\tauthor = {Harter, Philipp and Hauke, Jan and Heitz, Florian and Reuss, Alexander and Kommoss, Stefan and Marmé, Frederik and Heimbach, André and Prieske, Katharina and Richters, Lisa and Burges, Alexander and Neidhardt, Guido and de Gregorio, Nikolaus and El-Balat, Ahmed and Hilpert, Felix and Meier, Werner and Kimmig, Rainer and Kast, Karin and Sehouli, Jalid and Baumann, Klaus and Jackisch, Christian and Park-Simon, Tjoung-Won and Hanker, Lars and Kröber, Sandra and Pfisterer, Jacobus and Gevensleben, Heidrun and Schnelzer, Andreas and Dietrich, Dimo and Neunhöffer, Tanja and Krockenberger, Mathias and Brucker, Sara Y. and Nürnberg, Peter and Thiele, Holger and Altmüller, Janine and Lamla, Josefin and Elser, Gabriele and du Bois, Andreas and Hahnen, Eric and Schmutzler, Rita},\n\tmonth = oct,\n\tyear = {2017},\n\tpmid = {29053726},\n\tpmcid = {PMC5650145},\n\tkeywords = {BRCA1, BRCA1/2, BRCA2, Blood, CNV, Clinical study, Genomics, Hereditary Disorders, LGR, Ovarian Cancer, SOPHiA DDM},\n}\n\n

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\n \n\n \n \n \n \n \n \n T‐cell prolymphocytic leukemia and tuberculosis: a puzzling association.\n \n \n \n \n\n\n \n Cervera, P.; Gilhot, A.; Marzac, C.; Féger, F.; Tang, R.; Jaff, N.; and Coppo, P.\n\n\n \n\n\n\n Clinical Case Reports, 5(9): 1536–1541. August 2017.\n \n\n\n\n
\n\n\n\n \n \n $\"T‐cell$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{cervera_tcell_2017,\n\ttitle = {T‐cell prolymphocytic leukemia and tuberculosis: a puzzling association},\n\tvolume = {5},\n\tissn = {2050-0904},\n\tshorttitle = {T‐cell prolymphocytic leukemia and tuberculosis},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5582236/},\n\tdoi = {10.1002/ccr3.1121},\n\tnumber = {9},\n\turldate = {2020-02-11},\n\tjournal = {Clinical Case Reports},\n\tauthor = {Cervera, Pascale and Gilhot, Amélie and Marzac, Christophe and Féger, Frédéric and Tang, Ruoping and Jaff, Nabaz and Coppo, Paul},\n\tmonth = aug,\n\tyear = {2017},\n\tpmid = {28878921},\n\tpmcid = {PMC5582236},\n\tkeywords = {Blood, Genomics, Leukemia, Liquid tumor, SNV, SOPHiA DDM},\n\tpages = {1536--1541},\n}\n\n

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\n \n\n \n \n \n \n \n \n A New Targeted CFTR Mutation Panel Based on Next-Generation Sequencing Technology.\n \n \n \n \n\n\n \n Lucarelli, M.; Porcaro, L.; Biffignandi, A.; Costantino, L.; Giannone, V.; Alberti, L.; Bruno, S. M.; Corbetta, C.; Torresani, E.; Colombo, C.; and Seia, M.\n\n\n \n\n\n\n The Journal of Molecular Diagnostics, 19(5): 788–800. September 2017.\n \n\n\n\n
\n\n\n\n \n \n $\"A$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{lucarelli_new_2017,\n\ttitle = {A {New} {Targeted} {CFTR} {Mutation} {Panel} {Based} on {Next}-{Generation} {Sequencing} {Technology}},\n\tvolume = {19},\n\tissn = {1525-1578},\n\turl = {http://www.sciencedirect.com/science/article/pii/S1525157817301265},\n\tdoi = {10.1016/j.jmoldx.2017.06.002},\n\tabstract = {Searching for mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) is a key step in the diagnosis of and neonatal and carrier screening for cystic fibrosis (CF), and it has implications for prognosis and personalized therapy. The large number of mutations and genetic and phenotypic variability make this search a complex task. Herein, we developed, validated, and tested a laboratory assay for an extended search for mutations in CFTR using a next-generation sequencing–based method, with a panel of 188 CFTR mutations customized for the Italian population. Overall, 1426 dried blood spots from neonatal screening, 402 genomic DNA samples from various origins, and 1138 genomic DNA samples from patients with CF were analyzed. The assay showed excellent analytical and diagnostic operative characteristics. We identified and experimentally validated 159 (of 188) CFTR mutations. The assay achieved detection rates of 95.0\\% and 95.6\\% in two large-scale case series of CF patients from central and northern Italy, respectively. These detection rates are among the highest reported so far with a genetic test for CF based on a mutation panel. This assay appears to be well suited for diagnostics, neonatal and carrier screening, and assisted reproduction, and it represents a considerable advantage in CF genetic counseling.},\n\tlanguage = {en},\n\tnumber = {5},\n\turldate = {2020-02-11},\n\tjournal = {The Journal of Molecular Diagnostics},\n\tauthor = {Lucarelli, Marco and Porcaro, Luigi and Biffignandi, Alice and Costantino, Lucy and Giannone, Valentina and Alberti, Luisella and Bruno, Sabina Maria and Corbetta, Carlo and Torresani, Erminio and Colombo, Carla and Seia, Manuela},\n\tmonth = sep,\n\tyear = {2017},\n\tkeywords = {Blood, Bundle, CF, CFTR, CNV, Custom, Cystic Fibrosis, Genomic Hereditary Disorders, Genomics, Hereditary Disorders, Illumina Sequencer, Large panel, Liquid Biopsy, SOPHiA DDM, Targeted},\n\tpages = {788--800},\n}\n\n

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\n \n\n \n \n \n \n \n \n MET Exon 14 Alterations and New Resistance Mutations to Tyrosine Kinase Inhibitors: Risk of Inadequate Detection with Current Amplicon-Based NGS Panels.\n \n \n \n \n\n\n \n Poirot, B.; Doucet, L.; Benhenda, S.; Champ, J.; Meignin, V.; and Lehmann-Che, J.\n\n\n \n\n\n\n Journal of Thoracic Oncology, 12(10): 1582–1587. October 2017.\n \n\n\n\n
\n\n\n\n \n \n $\"MET$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{poirot_met_2017,\n\ttitle = {{MET} {Exon} 14 {Alterations} and {New} {Resistance} {Mutations} to {Tyrosine} {Kinase} {Inhibitors}: {Risk} of {Inadequate} {Detection} with {Current} {Amplicon}-{Based} {NGS} {Panels}},\n\tvolume = {12},\n\tissn = {1556-0864},\n\tshorttitle = {{MET} {Exon} 14 {Alterations} and {New} {Resistance} {Mutations} to {Tyrosine} {Kinase} {Inhibitors}},\n\turl = {http://www.sciencedirect.com/science/article/pii/S1556086417306573},\n\tdoi = {10.1016/j.jtho.2017.07.026},\n\tlanguage = {en},\n\tnumber = {10},\n\turldate = {2020-02-11},\n\tjournal = {Journal of Thoracic Oncology},\n\tauthor = {Poirot, Brigitte and Doucet, Ludovic and Benhenda, Shirine and Champ, Jérôme and Meignin, Véronique and Lehmann-Che, Jacqueline},\n\tmonth = oct,\n\tyear = {2017},\n\tkeywords = {EGFR, Genomics, HotSpot, INDEL, SOPHiA DDM, Solid Tumor, TKI, Targeted, Tyrosine Kinase Inhibitors},\n\tpages = {1582--1587},\n}\n\n

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\n \n\n \n \n \n \n \n \n Collaborative study to evaluate the proposed WHO 1st international reference panel for genomic KRAS codons 12 and 13 mutations.\n \n \n \n \n\n\n \n Sanzone, P.; Hawkins, R.; Atkinson, E.; Rigsby, P.; Boyle, J.; Organization, W. H.; and Standardization, W. E. C. o. B.\n\n\n \n\n\n\n Technical Report World Health Organization, October 2017.\n \n\n\n\n
\n\n\n\n \n \n $\"Collaborative$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@techreport{sanzone_collaborative_2017,\n\ttitle = {Collaborative study to evaluate the proposed {WHO} 1st international reference panel for genomic {KRAS} codons 12 and 13 mutations},\n\turl = {https://apps.who.int/iris/bitstream/handle/10665/260258/WHO-BS-2017.2317-eng.pdf},\n\tinstitution = {World Health Organization},\n\tauthor = {Sanzone, Pia and Hawkins, Ross and Atkinson, Eleanor and Rigsby, Peter and Boyle, Jennifer and Organization, World Health and Standardization, WHO Expert Committee on Biological},\n\tmonth = oct,\n\tyear = {2017},\n\tkeywords = {Collaborative study, Genomics, KRAS, SNV, SOPHiA DDM, WHO},\n}\n\n

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\n \n\n \n \n \n \n \n \n Age Is Not a Predictive Marker in Molecularly Annotated Elderly Patients with Myelofibrosis Treated with Ruxolitinib: a Multicenter Study on 277 Patients.\n \n \n \n \n\n\n \n Palandri, F.; Sapienza, M. R.; Palumbo, G. A.; Bonifacio, M.; Benevolo, G.; Abruzzese, E.; Martino, B.; Latagliata, R.; Polverelli, N.; Lemoli, R. M.; Tiribelli, M.; Breccia, M.; Cavazzini, F.; Binotto, G.; Tieghi, A.; Di Veroli, A.; Sgherza, N.; Isidori, A.; Ibatici, A.; Crugnola, M.; Bosi, C.; Trawinska, M. M.; Bartoletti, D.; Scaffidi, L.; Sabattini, E.; Martinelli, G.; Cavo, M.; Vianelli, N.; Catani, L.; and Heidel, F. H.\n\n\n \n\n\n\n Blood, 130(Supplement 1): 1642–1642. December 2017.\n \n\n\n\n
\n\n\n\n \n \n $\"Age$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{palandri_age_2017,\n\ttitle = {Age {Is} {Not} a {Predictive} {Marker} in {Molecularly} {Annotated} {Elderly} {Patients} with {Myelofibrosis} {Treated} with {Ruxolitinib}: a {Multicenter} {Study} on 277 {Patients}.},\n\tvolume = {130},\n\tissn = {0006-4971},\n\tshorttitle = {Age {Is} {Not} a {Predictive} {Marker} in {Molecularly} {Annotated} {Elderly} {Patients} with {Myelofibrosis} {Treated} with {Ruxolitinib}},\n\turl = {https://ashpublications.org/blood/article/130/Supplement 1/1642/79414/Age-Is-Not-a-Predictive-Marker-in-Molecularly},\n\tdoi = {10.1182/blood.V130.Suppl_1.1642.1642},\n\tabstract = {Abstract. Introduction. Ruxolitinib (RUX) is a JAK1/2 inhibitor that may control myelofibrosis (MF)-related splenomegaly and symptoms and can be prescribed reg},\n\tlanguage = {en},\n\tnumber = {Supplement 1},\n\turldate = {2020-02-11},\n\tjournal = {Blood},\n\tauthor = {Palandri, Francesca and Sapienza, Maria Rosaria and Palumbo, Giuseppe A. and Bonifacio, Massimiliano and Benevolo, Giulia and Abruzzese, Elisabetta and Martino, Bruno and Latagliata, Roberto and Polverelli, Nicola and Lemoli, Roberto Massimo and Tiribelli, Mario and Breccia, Massimo and Cavazzini, Francesco and Binotto, Gianni and Tieghi, Alessia and Di Veroli, Ambra and Sgherza, Nicola and Isidori, Alessandro and Ibatici, Adalberto and Crugnola, Monica and Bosi, Costanza and Trawinska, Malgorzata Monika and Bartoletti, Daniela and Scaffidi, Luigi and Sabattini, Elena and Martinelli, Giovanni and Cavo, Michele and Vianelli, Nicola and Catani, Lucia and Heidel, Florian H.},\n\tmonth = dec,\n\tyear = {2017},\n\tkeywords = {Clinical study, Commercial, Genomics, Illumina Sequencer, Liquid Biopsy, Liquid tumor, MYS, Oncology, SOPHiA DDM, Targeted},\n\tpages = {1642--1642},\n}\n\n

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\n \n\n \n \n \n \n \n \n Abstracts from the 23rd Italian congress of Cystic Fibrosis and the 13th National congress of Cystic Fibrosis Italian Society.\n \n \n \n \n\n\n \n Bevivino, A.; Coiana, A.; Fogazzi, A.; Timelli, F.; Signorini, S.; Lucarelli, M.; Morelli, P.; Padoan, R.; Giordani, B.; and Amato, A.\n\n\n \n\n\n\n In Italian journal of pediatrics, volume 44, pages 6, November 2017. Springer\n \n\n\n\n
\n\n\n\n \n \n $\"Abstracts$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@inproceedings{bevivino_abstracts_2017,\n\ttitle = {Abstracts from the 23rd {Italian} congress of {Cystic} {Fibrosis} and the 13th {National} congress of {Cystic} {Fibrosis} {Italian} {Society}},\n\tvolume = {44},\n\turl = {https://link.springer.com/article/10.1186/s13052-017-0430-4},\n\tbooktitle = {Italian journal of pediatrics},\n\tpublisher = {Springer},\n\tauthor = {Bevivino, Annamaria and Coiana, Alessandra and Fogazzi, Annalisa and Timelli, Fabiana and Signorini, Sandra and Lucarelli, Marco and Morelli, Patrizia and Padoan, Rita and Giordani, Barbara and Amato, Annalisa},\n\tmonth = nov,\n\tyear = {2017},\n\tpages = {6},\n}\n\n

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\n \n 2016\n \n \n (6)\n \n \n

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\n \n\n \n \n \n \n \n Mutations in eight small DFNB genes are not a frequent cause of non-syndromic hereditary hearing loss in Czech patients.\n \n \n \n\n\n \n Marková, S.; Šafka Brožková, D.; Mészárosová, A.; Neupauerová, J.; Groh, D.; Křečková, G.; Laššuthová, P.; and Seeman, P.\n\n\n \n\n\n\n International Journal of Pediatric Otorhinolaryngology, 86: 27–33. July 2016.\n \n\n\n\n
\n\n\n\n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{markova_mutations_2016,\n\ttitle = {Mutations in eight small {DFNB} genes are not a frequent cause of non-syndromic hereditary hearing loss in {Czech} patients},\n\tvolume = {86},\n\tissn = {1872-8464},\n\tdoi = {10.1016/j.ijporl.2016.04.005},\n\tabstract = {OBJECTIVES: To evaluate the contribution of eight small NSHL-AR (non-syndromic deafness, autosomal recessive) genes to hereditary hearing loss in Czech patients.\nPATIENTS AND METHODS: Unrelated Czech patients, adults and children, diagnosed with pre-lingual hereditary hearing loss with at least one similarly affected deaf sibling and with previously excluded mutations in the GJB2 gene were investigated by Sanger sequencing of the selected eight small NSHL-AR associated genes (CABP2 - 51 patients, CIB2 - 45 patients, PJVK/DFNB59 - 53 patients, GJB3 - 46 patients, ILDR1 - 48 patients, LHFPL5 - 66 patients, LRTOMT - 60 patients, TMIE - 64 patients).\nRESULTS: Mutations were detected in the LHFPL5 (DFNB67) gene. The patient is heterozygote for two already described pathogenic variants (p.Tyr127Cys, p.Thr165Met). In five samples, five rare heterozygous variants (two novel) predicted as pathogenic were detected in genes CABP2, ILDR1, LHFPL5 and LRTOMT.\nCONCLUSION: Mutations in eight small NSHL-AR genes are not a frequent cause of hereditary hearing loss in the Czech Republic. This diagnostic approach permitted the clarification of HL in only one patient - two heterozygous mutations were detected in LHFPL5 gene for the first time in Central Europe. As the use of panel base MPS certainly improves the diagnostic yield, future studies should rather profit from that diagnostic strategy.},\n\tlanguage = {eng},\n\tjournal = {International Journal of Pediatric Otorhinolaryngology},\n\tauthor = {Marková, Simona and Šafka Brožková, Dana and Mészárosová, Anna and Neupauerová, Jana and Groh, Daniel and Křečková, Gabriela and Laššuthová, Petra and Seeman, Pavel},\n\tmonth = jul,\n\tyear = {2016},\n\tpmid = {27260575},\n\tkeywords = {Alamut, Calcium-Binding Proteins, Child, Czech Republic, DFNB, DFNB67, Female, Genetic Markers, Genetic Predisposition to Disease, Hearing Loss, Sensorineural, Hereditary hearing loss, Heterozygote, Humans, LHFPL5, Male, Membrane Proteins, Mutation, NSHL-AR, Proteins, Receptors, Cell Surface, TMHS},\n\tpages = {27--33},\n}\n\n

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\n \n\n \n \n \n \n \n \n Crunch: Completely Automated Analysis of ChIP-seq Data.\n \n \n \n \n\n\n \n Berger, S.; Omidi, S.; Pachkov, M.; Arnold, P.; Kelley, N.; Salatino, S.; and Nimwegen, E. v.\n\n\n \n\n\n\n bioRxiv,042903. March 2016.\n \n\n\n\n
\n\n\n\n \n \n $\"Crunch:$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{berger_crunch_2016,\n\ttitle = {Crunch: {Completely} {Automated} {Analysis} of {ChIP}-seq {Data}},\n\tcopyright = {© 2016, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution-NonCommercial-NoDerivs 4.0 International), CC BY-NC-ND 4.0, as described at http://creativecommons.org/licenses/by-nc-nd/4.0/},\n\tshorttitle = {Crunch},\n\turl = {https://www.biorxiv.org/content/10.1101/042903v1},\n\tdoi = {10.1101/042903},\n\tlanguage = {en},\n\turldate = {2020-02-11},\n\tjournal = {bioRxiv},\n\tauthor = {Berger, Severin and Omidi, Saeed and Pachkov, Mikhail and Arnold, Phil and Kelley, Nicholas and Salatino, Silvia and Nimwegen, Erik van},\n\tmonth = mar,\n\tyear = {2016},\n\tpages = {042903},\n}\n\n

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\n \n\n \n \n \n \n \n \n Detection of somatic BRCA 1/2 mutations in ovarian cancer–next-generation sequencing analysis of 100 cases.\n \n \n \n \n\n\n \n Koczkowska, M.; Zuk, M.; Gorczynski, A.; Ratajska, M.; Lewandowska, M.; Biernat, W.; Limon, J.; and Wasag, B.\n\n\n \n\n\n\n Cancer medicine, 5(7): 1640–1646. May 2016.\n \n\n\n\n
\n\n\n\n \n \n $\"Detection$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{koczkowska_detection_2016,\n\ttitle = {Detection of somatic {BRCA} 1/2 mutations in ovarian cancer–next-generation sequencing analysis of 100 cases},\n\tvolume = {5},\n\turl = {https://onlinelibrary.wiley.com/doi/full/10.1002/cam4.748},\n\tnumber = {7},\n\tjournal = {Cancer medicine},\n\tauthor = {Koczkowska, Magdalena and Zuk, Monika and Gorczynski, Adam and Ratajska, Magdalena and Lewandowska, Marzena and Biernat, Wojciech and Limon, Janusz and Wasag, Bartosz},\n\tmonth = may,\n\tyear = {2016},\n\tkeywords = {Bundle, FFPE, Genomics, Illumina Sequencer, Oncology, SOPHiA DDM, Solid Tumor, Targeted},\n\tpages = {1640--1646},\n}\n\n

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\n \n\n \n \n \n \n \n \n Analysis of founder mutations in rare tumors associated with hereditary breast/ovarian cancer reveals a novel association of BRCA2 mutations with ampulla of Vater carcinomas.\n \n \n \n \n\n\n \n Pinto, P.; Peixoto, A.; Santos, C.; Rocha, P.; Pinto, C.; Pinheiro, M.; Leca, L.; Martins, A. T.; Ferreira, V.; and Bartosch, C.\n\n\n \n\n\n\n PloS one, 11(8). August 2016.\n \n\n\n\n
\n\n\n\n \n \n $\"Analysis$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

@article{pinto_analysis_2016,\n\ttitle = {Analysis of founder mutations in rare tumors associated with hereditary breast/ovarian cancer reveals a novel association of {BRCA2} mutations with ampulla of {Vater} carcinomas},\n\tvolume = {11},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988637/},\n\tnumber = {8},\n\tjournal = {PloS one},\n\tauthor = {Pinto, Pedro and Peixoto, Ana and Santos, Catarina and Rocha, Patricia and Pinto, Carla and Pinheiro, Manuela and Leca, Luis and Martins, Ana Teresa and Ferreira, Veronica and Bartosch, Carla},\n\tmonth = aug,\n\tyear = {2016},\n\tkeywords = {Alu, Ampulla of Vater Carcinomas, BRCA1, BRCA2, Blood, Breast cancer, Clinical study, FFPE, Genomics, Ovarian Cancer, Solid Tumor},\n}\n\n

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\n \n\n \n \n \n \n \n \n Amplicon Based Panel Targeted Resequencing Identified ZRSR2 As a Potential New Favorable Marker in Pediatric AML.\n \n \n \n \n\n\n \n Walter, C.; Xu, Z.; Zimmermann, M.; Reinhardt, D.; and Von Neuhoff, N.\n\n\n \n\n\n\n Blood, 128(22): 2905–2905. December 2016.\n \n\n\n\n
\n\n\n\n \n \n $\"Amplicon$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@article{walter_amplicon_2016,\n\ttitle = {Amplicon {Based} {Panel} {Targeted} {Resequencing} {Identified} {ZRSR2} {As} a {Potential} {New} {Favorable} {Marker} in {Pediatric} {AML}},\n\tvolume = {128},\n\tissn = {0006-4971},\n\turl = {https://ashpublications.org/blood/article/128/22/2905/113788/Amplicon-Based-Panel-Targeted-Resequencing},\n\tdoi = {10.1182/blood.V128.22.2905.2905},\n\tlanguage = {en},\n\tnumber = {22},\n\turldate = {2020-02-11},\n\tjournal = {Blood},\n\tauthor = {Walter, Christiane and Xu, Zhenyu and Zimmermann, Martin and Reinhardt, Dirk and Von Neuhoff, Nils},\n\tmonth = dec,\n\tyear = {2016},\n\tpages = {2905--2905},\n}\n\n

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\n \n\n \n \n \n \n \n \n Detection of NRAS, KRAS and BRAF mutations in FFPE derived DNA with a novel targeted resequencing-based diagnostics assay.\n \n \n \n \n\n\n \n Marques, C.; Bettens, K.; Goossens, D.; Heyrman, L.; Heusdens, C.; Kupers, S.; Berwouts, S.; Van Barel, D.; Rotthier, A.; and Del-Favero, J.\n\n\n \n\n\n\n European Society for Medical Oncology, October 2016.\n \n\n\n\n
\n\n\n\n \n \n $\"Detection$ Paper\n \n \n\n \n\n \n link\n \n \n\n bibtex\n \n\n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

@book{marques_detection_2016,\n\ttitle = {Detection of {NRAS}, {KRAS} and {BRAF} mutations in {FFPE} derived {DNA} with a novel targeted resequencing-based diagnostics assay},\n\turl = {https://academic.oup.com/annonc/article/27/suppl_6/1174P/2800021},\n\tpublisher = {European Society for Medical Oncology},\n\tauthor = {Marques, C. and Bettens, K. and Goossens, D. and Heyrman, L. and Heusdens, C. and Kupers, S. and Berwouts, S. and Van Barel, D. and Rotthier, A. and Del-Favero, J.},\n\tmonth = oct,\n\tyear = {2016},\n}\n\n

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