MGMT Expression Contributes to Temozolomide Resistance in H3K27M-Mutant Diffuse Midline Gliomas and MGMT Silencing to Temozolomide Sensitivity in IDH-Mutant Gliomas

Neurol Med Chir (Tokyo). 2018 Jul 15;58(7):290-295. doi: 10.2176/nmc.ra.2018-0044. Epub 2018 May 31.

Abstract

Histone H3 mutations are frequently found in diffuse midline gliomas (DMGs), which include diffuse intrinsic pontine gliomas and thalamic gliomas. These tumors have dismal prognoses. Recent evidence suggests that one reason for the poor prognoses is that O6-methylguanine-DNA methyltransferase (MGMT) promoter frequently lacks methylation in DMGs. This review compares the epigenetic changes brought about by histone mutations to those by isocitrate dehydrogenase-mutant gliomas, which frequently have methylated MGMT promoters and are known to be sensitive to temozolomide.

Keywords: Histone H3 mutation; MGMT; diffuse midline gliomas; epigenetics; resistance.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents, Alkylating / pharmacology*
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • DNA Modification Methylases / metabolism*
  • DNA Repair Enzymes / metabolism*
  • Drug Resistance, Neoplasm / genetics*
  • Glioblastoma / genetics*
  • Glioblastoma / metabolism
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Mutation / genetics
  • Promoter Regions, Genetic / genetics
  • Temozolomide / pharmacology*
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Antineoplastic Agents, Alkylating
  • Tumor Suppressor Proteins
  • Isocitrate Dehydrogenase
  • Jumonji Domain-Containing Histone Demethylases
  • Kdm6b protein, mouse
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • Temozolomide