@article{RN6075,
   author = {Oldrini, B. and Vaquero-Siguero, N. and Mu, Q. and Kroon, P. and Zhang, Y. and Galán-Ganga, M. and Bao, Z. and Wang, Z. and Liu, H. and Sa, J. K. and Zhao, J. and Kim, H. and Rodriguez-Perales, S. and Nam, D. H. and Verhaak, R. G. W. and Rabadan, R. and Jiang, T. and Wang, J. and Squatrito, M.},
   title = {MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas},
   journal = {Nat Commun},
   volume = {11},
   number = {1},
   pages = {3883},
   note = {2041-1723
Oldrini, Barbara
Vaquero-Siguero, Nuria
Mu, Quanhua
Kroon, Paula
Zhang, Ying
Galán-Ganga, Marcos
Bao, Zhaoshi
Orcid: 0000-0003-4922-4470
Wang, Zheng
Liu, Hanjie
Sa, Jason K
Orcid: 0000-0002-3251-5004
Zhao, Junfei
Kim, Hoon
Orcid: 0000-0003-4244-6126
Rodriguez-Perales, Sandra
Nam, Do-Hyun
Verhaak, Roel G W
Orcid: 0000-0003-2773-0436
Rabadan, Raul
Orcid: 0000-0001-7946-9255
Jiang, Tao
Orcid: 0000-0002-7008-6351
Wang, Jiguang
Orcid: 0000-0002-6923-4097
Squatrito, Massimo
Orcid: 0000-0002-4593-3790
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
England
2020/08/06
Nat Commun. 2020 Aug 4;11(1):3883. doi: 10.1038/s41467-020-17717-0.},
   abstract = {Temozolomide (TMZ) is an oral alkylating agent used for the treatment of glioblastoma and is now becoming a chemotherapeutic option in patients diagnosed with high-risk low-grade gliomas. The O-6-methylguanine-DNA methyltransferase (MGMT) is responsible for the direct repair of the main TMZ-induced toxic DNA adduct, the O6-Methylguanine lesion. MGMT promoter hypermethylation is currently the only known biomarker for TMZ response in glioblastoma patients. Here we show that a subset of recurrent gliomas carries MGMT genomic rearrangements that lead to MGMT overexpression, independently from changes in its promoter methylation. By leveraging the CRISPR/Cas9 technology we generated some of these MGMT rearrangements in glioma cells and demonstrated that the MGMT genomic rearrangements contribute to TMZ resistance both in vitro and in vivo. Lastly, we showed that such fusions can be detected in tumor-derived exosomes and could potentially represent an early detection marker of tumor recurrence in a subset of patients treated with TMZ.},
   keywords = {Adolescent
Adult
Aged
Animals
Brain Neoplasms/*drug therapy/genetics
Cell Line, Tumor
DNA Adducts/drug effects/metabolism
DNA Methylation
DNA Modification Methylases/*genetics/metabolism
DNA Repair Enzymes/*genetics/metabolism
Drug Resistance, Neoplasm/*genetics
Female
Gene Expression Regulation, Neoplastic
*Gene Rearrangement
Glioma/*drug therapy/genetics
Humans
Male
Mice
Middle Aged
Neoplasm Recurrence, Local/*genetics/prevention & control
Promoter Regions, Genetic/genetics
RNA-Seq
Temozolomide/*pharmacology/therapeutic use
Tumor Suppressor Proteins/*genetics/metabolism
Up-Regulation
Whole Genome Sequencing
Xenograft Model Antitumor Assays
Young Adult},
   ISSN = {2041-1723},
   DOI = {10.1038/s41467-020-17717-0},
   year = {2020},
   type = {Journal Article}
}

{"_id":"rm3yXgj7CamkZYJei","bibbaseid":"oldrini-vaquerosiguero-mu-kroon-zhang-galnganga-bao-wang-etal-mgmtgenomicrearrangementscontributetochemotherapyresistanceingliomas-2020","authorIDs":["c8zrScQz6casKGL4t"],"author_short":["Oldrini, B.","Vaquero-Siguero, N.","Mu, Q.","Kroon, P.","Zhang, Y.","Galán-Ganga, M.","Bao, Z.","Wang, Z.","Liu, H.","Sa, J. K.","Zhao, J.","Kim, H.","Rodriguez-Perales, S.","Nam, D. H.","Verhaak, R. G. W.","Rabadan, R.","Jiang, T.","Wang, J.","Squatrito, M."],"bibdata":{"bibtype":"article","type":"Journal Article","author":[{"propositions":[],"lastnames":["Oldrini"],"firstnames":["B."],"suffixes":[]},{"propositions":[],"lastnames":["Vaquero-Siguero"],"firstnames":["N."],"suffixes":[]},{"propositions":[],"lastnames":["Mu"],"firstnames":["Q."],"suffixes":[]},{"propositions":[],"lastnames":["Kroon"],"firstnames":["P."],"suffixes":[]},{"propositions":[],"lastnames":["Zhang"],"firstnames":["Y."],"suffixes":[]},{"propositions":[],"lastnames":["Galán-Ganga"],"firstnames":["M."],"suffixes":[]},{"propositions":[],"lastnames":["Bao"],"firstnames":["Z."],"suffixes":[]},{"propositions":[],"lastnames":["Wang"],"firstnames":["Z."],"suffixes":[]},{"propositions":[],"lastnames":["Liu"],"firstnames":["H."],"suffixes":[]},{"propositions":[],"lastnames":["Sa"],"firstnames":["J.","K."],"suffixes":[]},{"propositions":[],"lastnames":["Zhao"],"firstnames":["J."],"suffixes":[]},{"propositions":[],"lastnames":["Kim"],"firstnames":["H."],"suffixes":[]},{"propositions":[],"lastnames":["Rodriguez-Perales"],"firstnames":["S."],"suffixes":[]},{"propositions":[],"lastnames":["Nam"],"firstnames":["D.","H."],"suffixes":[]},{"propositions":[],"lastnames":["Verhaak"],"firstnames":["R.","G.","W."],"suffixes":[]},{"propositions":[],"lastnames":["Rabadan"],"firstnames":["R."],"suffixes":[]},{"propositions":[],"lastnames":["Jiang"],"firstnames":["T."],"suffixes":[]},{"propositions":[],"lastnames":["Wang"],"firstnames":["J."],"suffixes":[]},{"propositions":[],"lastnames":["Squatrito"],"firstnames":["M."],"suffixes":[]}],"title":"MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas","journal":"Nat Commun","volume":"11","number":"1","pages":"3883","note":"2041-1723 Oldrini, Barbara Vaquero-Siguero, Nuria Mu, Quanhua Kroon, Paula Zhang, Ying Galán-Ganga, Marcos Bao, Zhaoshi Orcid: 0000-0003-4922-4470 Wang, Zheng Liu, Hanjie Sa, Jason K Orcid: 0000-0002-3251-5004 Zhao, Junfei Kim, Hoon Orcid: 0000-0003-4244-6126 Rodriguez-Perales, Sandra Nam, Do-Hyun Verhaak, Roel G W Orcid: 0000-0003-2773-0436 Rabadan, Raul Orcid: 0000-0001-7946-9255 Jiang, Tao Orcid: 0000-0002-7008-6351 Wang, Jiguang Orcid: 0000-0002-6923-4097 Squatrito, Massimo Orcid: 0000-0002-4593-3790 Journal Article Observational Study Research Support, Non-U.S. Gov't England 2020/08/06 Nat Commun. 2020 Aug 4;11(1):3883. doi: 10.1038/s41467-020-17717-0.","abstract":"Temozolomide (TMZ) is an oral alkylating agent used for the treatment of glioblastoma and is now becoming a chemotherapeutic option in patients diagnosed with high-risk low-grade gliomas. The O-6-methylguanine-DNA methyltransferase (MGMT) is responsible for the direct repair of the main TMZ-induced toxic DNA adduct, the O6-Methylguanine lesion. MGMT promoter hypermethylation is currently the only known biomarker for TMZ response in glioblastoma patients. Here we show that a subset of recurrent gliomas carries MGMT genomic rearrangements that lead to MGMT overexpression, independently from changes in its promoter methylation. By leveraging the CRISPR/Cas9 technology we generated some of these MGMT rearrangements in glioma cells and demonstrated that the MGMT genomic rearrangements contribute to TMZ resistance both in vitro and in vivo. Lastly, we showed that such fusions can be detected in tumor-derived exosomes and could potentially represent an early detection marker of tumor recurrence in a subset of patients treated with TMZ.","keywords":"Adolescent Adult Aged Animals Brain Neoplasms/*drug therapy/genetics Cell Line, Tumor DNA Adducts/drug effects/metabolism DNA Methylation DNA Modification Methylases/*genetics/metabolism DNA Repair Enzymes/*genetics/metabolism Drug Resistance, Neoplasm/*genetics Female Gene Expression Regulation, Neoplastic *Gene Rearrangement Glioma/*drug therapy/genetics Humans Male Mice Middle Aged Neoplasm Recurrence, Local/*genetics/prevention & control Promoter Regions, Genetic/genetics RNA-Seq Temozolomide/*pharmacology/therapeutic use Tumor Suppressor Proteins/*genetics/metabolism Up-Regulation Whole Genome Sequencing Xenograft Model Antitumor Assays Young Adult","issn":"2041-1723","doi":"10.1038/s41467-020-17717-0","year":"2020","bibtex":"@article{RN6075,\n author = {Oldrini, B. and Vaquero-Siguero, N. and Mu, Q. and Kroon, P. and Zhang, Y. and Galán-Ganga, M. and Bao, Z. and Wang, Z. and Liu, H. and Sa, J. K. and Zhao, J. and Kim, H. and Rodriguez-Perales, S. and Nam, D. H. and Verhaak, R. G. W. and Rabadan, R. and Jiang, T. and Wang, J. and Squatrito, M.},\n title = {MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas},\n journal = {Nat Commun},\n volume = {11},\n number = {1},\n pages = {3883},\n note = {2041-1723\nOldrini, Barbara\nVaquero-Siguero, Nuria\nMu, Quanhua\nKroon, Paula\nZhang, Ying\nGalán-Ganga, Marcos\nBao, Zhaoshi\nOrcid: 0000-0003-4922-4470\nWang, Zheng\nLiu, Hanjie\nSa, Jason K\nOrcid: 0000-0002-3251-5004\nZhao, Junfei\nKim, Hoon\nOrcid: 0000-0003-4244-6126\nRodriguez-Perales, Sandra\nNam, Do-Hyun\nVerhaak, Roel G W\nOrcid: 0000-0003-2773-0436\nRabadan, Raul\nOrcid: 0000-0001-7946-9255\nJiang, Tao\nOrcid: 0000-0002-7008-6351\nWang, Jiguang\nOrcid: 0000-0002-6923-4097\nSquatrito, Massimo\nOrcid: 0000-0002-4593-3790\nJournal Article\nObservational Study\nResearch Support, Non-U.S. Gov't\nEngland\n2020/08/06\nNat Commun. 2020 Aug 4;11(1):3883. doi: 10.1038/s41467-020-17717-0.},\n abstract = {Temozolomide (TMZ) is an oral alkylating agent used for the treatment of glioblastoma and is now becoming a chemotherapeutic option in patients diagnosed with high-risk low-grade gliomas. The O-6-methylguanine-DNA methyltransferase (MGMT) is responsible for the direct repair of the main TMZ-induced toxic DNA adduct, the O6-Methylguanine lesion. MGMT promoter hypermethylation is currently the only known biomarker for TMZ response in glioblastoma patients. Here we show that a subset of recurrent gliomas carries MGMT genomic rearrangements that lead to MGMT overexpression, independently from changes in its promoter methylation. By leveraging the CRISPR/Cas9 technology we generated some of these MGMT rearrangements in glioma cells and demonstrated that the MGMT genomic rearrangements contribute to TMZ resistance both in vitro and in vivo. Lastly, we showed that such fusions can be detected in tumor-derived exosomes and could potentially represent an early detection marker of tumor recurrence in a subset of patients treated with TMZ.},\n keywords = {Adolescent\nAdult\nAged\nAnimals\nBrain Neoplasms/*drug therapy/genetics\nCell Line, Tumor\nDNA Adducts/drug effects/metabolism\nDNA Methylation\nDNA Modification Methylases/*genetics/metabolism\nDNA Repair Enzymes/*genetics/metabolism\nDrug Resistance, Neoplasm/*genetics\nFemale\nGene Expression Regulation, Neoplastic\n*Gene Rearrangement\nGlioma/*drug therapy/genetics\nHumans\nMale\nMice\nMiddle Aged\nNeoplasm Recurrence, Local/*genetics/prevention & control\nPromoter Regions, Genetic/genetics\nRNA-Seq\nTemozolomide/*pharmacology/therapeutic use\nTumor Suppressor Proteins/*genetics/metabolism\nUp-Regulation\nWhole Genome Sequencing\nXenograft Model Antitumor Assays\nYoung Adult},\n ISSN = {2041-1723},\n DOI = {10.1038/s41467-020-17717-0},\n year = {2020},\n type = {Journal Article}\n}\n\n","author_short":["Oldrini, B.","Vaquero-Siguero, N.","Mu, Q.","Kroon, P.","Zhang, Y.","Galán-Ganga, M.","Bao, Z.","Wang, Z.","Liu, H.","Sa, J. 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