Epigenetic reprogramming in pediatric gliomas: from molecular mechanisms to therapeutic implications

Trends Cancer. 2024 Dec;10(12):1147-1160. doi: 10.1016/j.trecan.2024.09.007. Epub 2024 Oct 10.

Abstract

Brain tumors in children and adults differ greatly in patient outcomes and responses to radiotherapy and chemotherapy. Moreover, the prevalence of recurrent mutations in histones and chromatin regulatory proteins in pediatric and young adult gliomas suggests that the chromatin landscape is rewired to support oncogenic programs. These early somatic mutations dysregulate widespread genomic loci by altering the distribution of histone post-translational modifications (PTMs) and, in consequence, causing changes in chromatin accessibility and in the histone code, leading to gene transcriptional changes. We review how distinct chromatin imbalances in glioma subtypes impact on oncogenic features such as cellular fate, proliferation, immune landscape, and radio resistance. Understanding these mechanisms of epigenetic dysregulation carries substantial implications for advancing targeted epigenetic therapies.

Keywords: H3G34R; H3K27M; diffuse hemispheric glioma (DHG); diffuse midline glioma (DMG); pediatric diffuse high-grade gliomas (pHGGs).

Publication types

  • Review

MeSH terms

  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / pathology
  • Brain Neoplasms* / therapy
  • Child
  • Chromatin / genetics
  • Chromatin / metabolism
  • Epigenesis, Genetic* / drug effects
  • Gene Expression Regulation, Neoplastic
  • Glioma* / drug therapy
  • Glioma* / genetics
  • Glioma* / pathology
  • Glioma* / therapy
  • Histones / metabolism
  • Humans
  • Mutation
  • Protein Processing, Post-Translational

Substances

  • Histones
  • Chromatin