MGMT

Overview

MGMT (O6-methylguanine-DNA methyltransferase) is a DNA repair enzyme that removes alkyl adducts from the O6 position of guanine. MGMT promoter methylation silences the gene, impairing repair of temozolomide-induced DNA damage and predicting response to alkylating chemotherapy in gliomas.

Alterations observed in the corpus

  • MGMT promoter methylation status assessed by DNA methylation array in IDH-mutant gliomas; relevant to temozolomide (TMZ) response; study analyzed epigenetic evolution of glioma under treatment PMID:38117484.
  • MGMT promoter methylation is a common feature in glioblastoma and a prerequisite for the hypermutator phenotype in recurrent tumors after temozolomide treatment if mismatch repair is compromised PMID:18772890.
  • Promoter DNA methylation in 48.5% of GBM (n=543); predictive of temozolomide response specifically in the classical GBM subtype (p=0.01) but not proneural, mesenchymal, or neural subtypes PMID:24120142
  • Low expression and/or VUS used to support temozolomide selection in PanNET patients PN26 and PN28 in a WGTA study of rare metastatic neuroendocrine neoplasms PMID:24326773
  • Aberrant promoter DNA methylation observed in hypermutated low-grade glioma recurrences after temozolomide (TMZ) treatment, consistent with reduced MGMT-mediated repair of TMZ-induced O6-methylguanine adducts driving the hypermutator phenotype PMID:24336570
  • MGMT epigenetic silencing enriched in the proximal hypermethylated GEA-CIN cluster 1 (oesophagus/proximal-stomach); raises the prospect of differential alkylating-agent response in esophageal/gastroesophageal adenocarcinoma PMID:28052061

Cancer types (linked)

  • IDH-mutant glioma (astrocytoma, diffuse glioma) — MGMT promoter methylation assessed as a co-variable in the epigenetic evolution study; standard biomarker for TMZ response in clinical practice PMID:38117484.
  • Glioblastoma (GB) — Identified as a core pathway component and biomarker; MGMT methylation is linked to both treatment response and potential for hypermutation PMID:18772890.

Co-occurrence and mutual exclusivity

  • MGMT promoter methylation commonly co-occurs with IDH1/IDH2 mutations in lower-grade gliomas (GCIMP phenotype); however, the relationship is not absolute PMID:38117484.

Therapeutic relevance

  • MGMT promoter methylation predicts sensitivity to temozolomide; methylated MGMT tumors are expected to benefit more from alkylating chemotherapy PMID:38117484.
  • MGMT methylation serves as a biomarker for response to alkylating agents like temozolomide in glioblastoma PMID:18772890.

Open questions

  • The interaction between MGMT methylation status, treatment-induced MSH6 mutations, and subsequent hypermutation in recurrent gliomas is not fully characterized in this corpus.

Sources

This page was processed by crosslinker on 2026-05-09. - PMID:24120142

This page was processed by crosslinker on 2026-05-09. - PMID:24326773

This page was processed by crosslinker on 2026-05-09. - PMID:24336570

This page was processed by crosslinker on 2026-05-09. - PMID:28052061

This page was processed by entity-page-writer on 2026-05-15.