Extent and prognostic value of MGMT promotor methylation in glioma WHO grade II

Sci Rep. 2020 Nov 12;10(1):19758. doi: 10.1038/s41598-020-76312-x.

Abstract

MGMT promotor methylation is associated with favourable outcome in high-grade glioma. In glioma WHO grade II, it is unclear whether the extent of MGMT promotor methylation and its prognostic role is independent from other molecular markers. We performed a retrospective analysis of 155 patients with glioma WHO grade II. First, all 155 patients were assigned to three molecular groups according to the 2016 WHO classification system: (1) oligodendroglioma, IDH-mutant and 1p19q co-deleted (n = 81); (2) astrocytoma, IDH-mutant and 1p19q non-codeleted (n = 54); (3) astrocytoma, IDH-wildtype (n = 20). MGMT promotor methylation was quantified using Sanger sequencing of the CpG sites 74-98 within the MGMT promotor region. Highest numbers of methylated CpG sites were found for oligodendroglioma, IDH-mutant and 1p19q co-deleted. When 1p19q co-deletion was absent, numbers of methylated CpG sites were higher in the presence of IDH-mutation. Accordingly, lowest numbers were seen in the IDH-wildtype subpopulation. In the entire cohort, larger numbers of methylated CpG sites were associated with favourable outcome. When analysed separately for the three WHO subgroups, a similar association was only retained in astrocytoma, IDH-wildtype. Collectively, extent of MGMT promotor methylation was strongly associated with other molecular markers and added prognostic information in astrocytoma, IDH-wildtype. Evaluation in prospective cohorts is warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Combined Modality Therapy
  • DNA Methylation*
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Glioma / genetics
  • Glioma / pathology*
  • Glioma / therapy
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Grading
  • Promoter Regions, Genetic*
  • Retrospective Studies
  • Survival Rate
  • Tumor Suppressor Proteins / genetics*

Substances

  • Biomarkers, Tumor
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes