MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas

Dataset ID Technology Samples
EGAD00001006281 Illumina HiSeq 2500 136

Dataset Description

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 carry 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 they lead 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.

Data Use Conditions


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Label Code Version Modifier
health or medical or biomedical research DUO:0000006 2019-01-07
research use only DUO:0000014 2019-01-07
time limit on use DUO:0000025 2019-01-07
project specific restriction DUO:0000027 2019-01-07