Background
- How MGMT promoter methylation status affects survival in IDH-mutant astrocytomas is less understood than in IDH-wildtype GBM.
- MGMT is a DNA repair enzyme
- Alleviates temozolomide damaged lesions
- High MGMT expression leads to resistance to temozolomide
- Hypermethylation of MGMT promoter leads to silencing of transcription, increasing sensitivity to temozolomide
- IDH mutants lose native enzymatic activity
- Acquires novel activity to promote epigenetic changes
- Leads to Glioma CpG Island Methylation Phenotype (G-CIMP)
- Multiple techniques measure MGMT promoter methylation:
- Pyrosequencing
- Methylation-specific polymerase chain reaction (PCR)
- Direct Sanger sequencing
- Limitations include low quantitative accuracy, short read length, and low sample throughput
- We used a large database of next-generation sequencing (NGS) and whole-transcriptome sequencing (WTS) performed in a single laboratory to determine the role of MGMT status on survival in IDH-mutant astrocytomas and in GBM.