@article{RN6150,
   author = {Yoshihara, K. and Wang, Q. and Torres-Garcia, W. and Zheng, S. and Vegesna, R. and Kim, H. and Verhaak, R. G.},
   title = {The landscape and therapeutic relevance of cancer-associated transcript fusions},
   journal = {Oncogene},
   volume = {34},
   number = {37},
   pages = {4845-54},
   note = {1476-5594
Yoshihara, K
Wang, Q
Torres-Garcia, W
Zheng, S
Vegesna, R
Kim, H
Verhaak, R G W
P30 CA016672/CA/NCI NIH HHS/United States
CA143883/CA/NCI NIH HHS/United States
P50 CA083639/CA/NCI NIH HHS/United States
U24 CA143883/CA/NCI NIH HHS/United States
CA083639/CA/NCI NIH HHS/United States
Journal Article
Research Support, N.I.H., Extramural
England
2014/12/17
Oncogene. 2015 Sep 10;34(37):4845-54. doi: 10.1038/onc.2014.406. Epub 2014 Dec 15.},
   abstract = {Transcript fusions as a result of chromosomal rearrangements have been a focus of attention in cancer as they provide attractive therapeutic targets. To identify novel fusion transcripts with the potential to be exploited therapeutically, we analyzed RNA sequencing, DNA copy number and gene mutation data from 4366 primary tumor samples. To avoid false positives, we implemented stringent quality criteria that included filtering of fusions detected in RNAseq data from 364 normal tissue samples. Our analysis identified 7887 high confidence fusion transcripts across 13 tumor types. Our fusion prediction was validated by evidence of a genomic rearrangement for 78 of 79 fusions in 48 glioma samples where whole-genome sequencing data were available. Cancers with higher levels of genomic instability showed a corresponding increase in fusion transcript frequency, whereas tumor samples harboring fusions contained statistically significantly fewer driver gene mutations, suggesting an important role for tumorigenesis. We identified at least one in-frame protein kinase fusion in 324 of 4366 samples (7.4%). Potentially druggable kinase fusions involving ALK, ROS, RET, NTRK and FGFR gene families were detected in bladder carcinoma (3.3%), glioblastoma (4.4%), head and neck cancer (1.0%), low-grade glioma (1.5%), lung adenocarcinoma (1.6%), lung squamous cell carcinoma (2.3%) and thyroid carcinoma (8.7%), suggesting a potential for application of kinase inhibitors across tumor types. In-frame fusion transcripts involving histone methyltransferase or histone demethylase genes were detected in 111 samples (2.5%) and may additionally be considered as therapeutic targets. In summary, we described the landscape of transcript fusions detected across a large number of tumor samples and revealed fusion events with clinical relevance that have not been previously recognized. Our results support the concept of basket clinical trials where patients are matched with experimental therapies based on their genomic profile rather than the tissue where the tumor originated.},
   keywords = {Cell Transformation, Neoplastic/*genetics
Chromatin Assembly and Disassembly/genetics
Computational Biology
DNA Mutational Analysis/methods
Gene Expression Profiling
Genetic Heterogeneity
Humans
*Molecular Targeted Therapy/methods
Neoplasms/classification/*genetics/*therapy
Oncogene Proteins, Fusion/*genetics
RNA, Messenger/genetics
RNA, Neoplasm/genetics
Sequence Alignment},
   ISSN = {0950-9232 (Print)
0950-9232},
   DOI = {10.1038/onc.2014.406},
   year = {2015},
   type = {Journal Article}
}

{"_id":"xNbiwvzcsSksynFsW","bibbaseid":"yoshihara-wang-torresgarcia-zheng-vegesna-kim-verhaak-thelandscapeandtherapeuticrelevanceofcancerassociatedtranscriptfusions-2015","authorIDs":["5dce3b23dcea22df0100007c","5dec52fce16431f2010000c9","5dec5944e16431f2010000fa","5e0a5e7ace3ebce40100010e","5e2ff5be5bfc8ede0100003b","c8zrScQz6casKGL4t"],"author_short":["Yoshihara, K.","Wang, Q.","Torres-Garcia, W.","Zheng, S.","Vegesna, R.","Kim, H.","Verhaak, R. G."],"bibdata":{"bibtype":"article","type":"Journal Article","author":[{"propositions":[],"lastnames":["Yoshihara"],"firstnames":["K."],"suffixes":[]},{"propositions":[],"lastnames":["Wang"],"firstnames":["Q."],"suffixes":[]},{"propositions":[],"lastnames":["Torres-Garcia"],"firstnames":["W."],"suffixes":[]},{"propositions":[],"lastnames":["Zheng"],"firstnames":["S."],"suffixes":[]},{"propositions":[],"lastnames":["Vegesna"],"firstnames":["R."],"suffixes":[]},{"propositions":[],"lastnames":["Kim"],"firstnames":["H."],"suffixes":[]},{"propositions":[],"lastnames":["Verhaak"],"firstnames":["R.","G."],"suffixes":[]}],"title":"The landscape and therapeutic relevance of cancer-associated transcript fusions","journal":"Oncogene","volume":"34","number":"37","pages":"4845-54","note":"1476-5594 Yoshihara, K Wang, Q Torres-Garcia, W Zheng, S Vegesna, R Kim, H Verhaak, R G W P30 CA016672/CA/NCI NIH HHS/United States CA143883/CA/NCI NIH HHS/United States P50 CA083639/CA/NCI NIH HHS/United States U24 CA143883/CA/NCI NIH HHS/United States CA083639/CA/NCI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural England 2014/12/17 Oncogene. 2015 Sep 10;34(37):4845-54. doi: 10.1038/onc.2014.406. Epub 2014 Dec 15.","abstract":"Transcript fusions as a result of chromosomal rearrangements have been a focus of attention in cancer as they provide attractive therapeutic targets. To identify novel fusion transcripts with the potential to be exploited therapeutically, we analyzed RNA sequencing, DNA copy number and gene mutation data from 4366 primary tumor samples. To avoid false positives, we implemented stringent quality criteria that included filtering of fusions detected in RNAseq data from 364 normal tissue samples. Our analysis identified 7887 high confidence fusion transcripts across 13 tumor types. Our fusion prediction was validated by evidence of a genomic rearrangement for 78 of 79 fusions in 48 glioma samples where whole-genome sequencing data were available. Cancers with higher levels of genomic instability showed a corresponding increase in fusion transcript frequency, whereas tumor samples harboring fusions contained statistically significantly fewer driver gene mutations, suggesting an important role for tumorigenesis. We identified at least one in-frame protein kinase fusion in 324 of 4366 samples (7.4%). Potentially druggable kinase fusions involving ALK, ROS, RET, NTRK and FGFR gene families were detected in bladder carcinoma (3.3%), glioblastoma (4.4%), head and neck cancer (1.0%), low-grade glioma (1.5%), lung adenocarcinoma (1.6%), lung squamous cell carcinoma (2.3%) and thyroid carcinoma (8.7%), suggesting a potential for application of kinase inhibitors across tumor types. In-frame fusion transcripts involving histone methyltransferase or histone demethylase genes were detected in 111 samples (2.5%) and may additionally be considered as therapeutic targets. In summary, we described the landscape of transcript fusions detected across a large number of tumor samples and revealed fusion events with clinical relevance that have not been previously recognized. Our results support the concept of basket clinical trials where patients are matched with experimental therapies based on their genomic profile rather than the tissue where the tumor originated.","keywords":"Cell Transformation, Neoplastic/*genetics Chromatin Assembly and Disassembly/genetics Computational Biology DNA Mutational Analysis/methods Gene Expression Profiling Genetic Heterogeneity Humans *Molecular Targeted Therapy/methods Neoplasms/classification/*genetics/*therapy Oncogene Proteins, Fusion/*genetics RNA, Messenger/genetics RNA, Neoplasm/genetics Sequence Alignment","issn":"0950-9232 (Print) 0950-9232","doi":"10.1038/onc.2014.406","year":"2015","bibtex":"@article{RN6150,\n author = {Yoshihara, K. and Wang, Q. and Torres-Garcia, W. and Zheng, S. and Vegesna, R. and Kim, H. and Verhaak, R. G.},\n title = {The landscape and therapeutic relevance of cancer-associated transcript fusions},\n journal = {Oncogene},\n volume = {34},\n number = {37},\n pages = {4845-54},\n note = {1476-5594\nYoshihara, K\nWang, Q\nTorres-Garcia, W\nZheng, S\nVegesna, R\nKim, H\nVerhaak, R G W\nP30 CA016672/CA/NCI NIH HHS/United States\nCA143883/CA/NCI NIH HHS/United States\nP50 CA083639/CA/NCI NIH HHS/United States\nU24 CA143883/CA/NCI NIH HHS/United States\nCA083639/CA/NCI NIH HHS/United States\nJournal Article\nResearch Support, N.I.H., Extramural\nEngland\n2014/12/17\nOncogene. 2015 Sep 10;34(37):4845-54. doi: 10.1038/onc.2014.406. Epub 2014 Dec 15.},\n abstract = {Transcript fusions as a result of chromosomal rearrangements have been a focus of attention in cancer as they provide attractive therapeutic targets. To identify novel fusion transcripts with the potential to be exploited therapeutically, we analyzed RNA sequencing, DNA copy number and gene mutation data from 4366 primary tumor samples. To avoid false positives, we implemented stringent quality criteria that included filtering of fusions detected in RNAseq data from 364 normal tissue samples. Our analysis identified 7887 high confidence fusion transcripts across 13 tumor types. Our fusion prediction was validated by evidence of a genomic rearrangement for 78 of 79 fusions in 48 glioma samples where whole-genome sequencing data were available. Cancers with higher levels of genomic instability showed a corresponding increase in fusion transcript frequency, whereas tumor samples harboring fusions contained statistically significantly fewer driver gene mutations, suggesting an important role for tumorigenesis. We identified at least one in-frame protein kinase fusion in 324 of 4366 samples (7.4%). Potentially druggable kinase fusions involving ALK, ROS, RET, NTRK and FGFR gene families were detected in bladder carcinoma (3.3%), glioblastoma (4.4%), head and neck cancer (1.0%), low-grade glioma (1.5%), lung adenocarcinoma (1.6%), lung squamous cell carcinoma (2.3%) and thyroid carcinoma (8.7%), suggesting a potential for application of kinase inhibitors across tumor types. In-frame fusion transcripts involving histone methyltransferase or histone demethylase genes were detected in 111 samples (2.5%) and may additionally be considered as therapeutic targets. In summary, we described the landscape of transcript fusions detected across a large number of tumor samples and revealed fusion events with clinical relevance that have not been previously recognized. Our results support the concept of basket clinical trials where patients are matched with experimental therapies based on their genomic profile rather than the tissue where the tumor originated.},\n keywords = {Cell Transformation, Neoplastic/*genetics\nChromatin Assembly and Disassembly/genetics\nComputational Biology\nDNA Mutational Analysis/methods\nGene Expression Profiling\nGenetic Heterogeneity\nHumans\n*Molecular Targeted Therapy/methods\nNeoplasms/classification/*genetics/*therapy\nOncogene Proteins, Fusion/*genetics\nRNA, Messenger/genetics\nRNA, Neoplasm/genetics\nSequence Alignment},\n ISSN = {0950-9232 (Print)\n0950-9232},\n DOI = {10.1038/onc.2014.406},\n year = {2015},\n type = {Journal Article}\n}\n\n","author_short":["Yoshihara, K.","Wang, Q.","Torres-Garcia, W.","Zheng, S.","Vegesna, R.","Kim, H.","Verhaak, R. 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