| Accession |
PRJCA001580 |
| Title |
MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas |
| Relevance |
Medical |
| Data types |
Transcriptome or Gene expression
Raw sequence reads
|
| Organisms |
Homo sapiens
|
| 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 gliomas1. 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 patients2. 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. |
| Sample scope |
Multiisolate |
| Release date |
2019-07-15 |
| Publication |
| PubMed ID |
Article title |
Journal name |
DOI |
Year |
| 32753598
|
MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas
|
Nature Communications
|
10.1038/s41467-020-17717-0
|
2020
|
|
|
| Grants |
| Agency |
program |
Grant ID |
Grant title |
| National Natural Science Foundation of China (NSFC)
|
International (Regional) Joint Research Programs
|
81761168038
|
|
|
|
| Submitter |
Tao
Jiang (taojiang1964@163.com)
|
| Organization |
Beijing Neurosurgical Institute |
| Submission date |
2019-07-15 |
