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Association of MGMT status with survival in low and high-grade IDH-mutant astrocytomas

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. 
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