2026-07-23T17:42:59Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/109582024-11-29T21:18:47Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Vaquero-Siguero, Nuria author Mu, Quanhua author Kroon, Paula author Zhang, Ying author Galán-Ganga, Marcos author Bao, Zhaoshi author Wang, Zheng author Liu, Hanjie author Zhao, Junfei author Kim, Hoon author Rodriguez-Perales, Sandra author Nam, Do-Hyun author Verhaak, Roel G W author Rabadan, Raul author Jiang, Tao author Wang, Jiguang author Oldrini, Barbara author Squatrito, Massimo author Sa, Jason K author Verhaak, Roel G. W. author 2020 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. Nat Commun . 2020 ;11(1):3883. 10.1038/s41467-020-17717-0 2041-1723 Nature communications 32753598 http://hdl.handle.net/20.500.12105/10958 PROMOTER METHYLATION RNA-SEQ GLIOBLASTOMA TEMOZOLOMIDE GENE BENEFIT MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas.