Association of MGMT Gene Promoter Methylation With Clinicopathological Parameters in Patients With Wild-type IDH Glioblastoma

Anticancer Res. 2022 Jan;42(1):335-341. doi: 10.21873/anticanres.15490.

Abstract

Background: The methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter plays a key role in response to temozolomide chemotherapy and disease prognosis in patients with wild-type isocitrate dehydrogenase (IDH) glioblastoma (GBM).

Patients and methods: The MGMT promoter methylation status and its association with clinicopathological parameters were retrospectively analysed in a cohort of 316 patients with GBM with wild-type IDH.

Results: MGMT methylation was significantly associated with ATRX chromatin remodeler (ATRX) loss and completion of the standard Stupp protocol. The median durations of overall and progression-free survival for the unmethylated, low-methylated (10-39%), and hypermethylated (≥40%) groups were 15, 23, and 30 months and 11, 18, and 21 months, respectively. However, the improvement in the survival of the hypermethylated group was not statistically significant.

Conclusion: We suggest a possible association between MGMT methylation status and ATRX mutations in GBM with wild-type IDH.

Keywords: ATRX loss; MGMT; glioblastoma; hypermethylation; low methylation; methylation status; temozolomide chemotherapy; wild-type IDH.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • DNA Methylation / drug effects
  • DNA Methylation / genetics*
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Female
  • Glioblastoma / diagnosis
  • Glioblastoma / drug therapy*
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Male
  • Middle Aged
  • Mutation / drug effects
  • Prognosis
  • Progression-Free Survival
  • Promoter Regions, Genetic / genetics
  • Retrospective Studies
  • Temozolomide / administration & dosage
  • Temozolomide / adverse effects
  • Tumor Suppressor Proteins / genetics*
  • X-linked Nuclear Protein / genetics*

Substances

  • Biomarkers, Tumor
  • Tumor Suppressor Proteins
  • Isocitrate Dehydrogenase
  • DNA Modification Methylases
  • MGMT protein, human
  • ATRX protein, human
  • X-linked Nuclear Protein
  • DNA Repair Enzymes
  • Temozolomide