Oncohistones in brain tumors: the soil and seed

Trends Cancer. 2023 May;9(5):444-455. doi: 10.1016/j.trecan.2023.02.003. Epub 2023 Mar 16.


Recurrent somatic mutations in histone 3 (H3) variants (termed 'oncohistones') have been identified in high-grade gliomas (HGGs) in children and young adults and induce tumorigenesis through disruption of chromatin states. Oncohistones occur with exquisite neuroanatomical specificity and are associated with specific age distribution and epigenome landscapes. Here, we review the known intrinsic ('seed') and the extrinsic ('soil') factors needed for their optimal oncogenic effect and highlight the many unresolved questions regarding their effects on development and crosstalk with the tumor microenvironment. The 'seed and soil' analogy, used to explain tumor metastatic niches, also applies to oncohistones, which mainly thrive and flourish in specific chromatin states during very narrow windows of development, creating exquisite vulnerabilities, which could provide effective therapies for these deadly cancers.

Keywords: EZHIP; G34R/V; K27M; PRC2; development; epigenome; gliomas; oncohistones.

Publication types

  • Review

MeSH terms

  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / pathology
  • Carcinogenesis / genetics
  • Child
  • Chromatin
  • Glioma* / genetics
  • Glioma* / pathology
  • Histones / genetics
  • Humans
  • Tumor Microenvironment / genetics
  • Young Adult


  • Histones
  • Chromatin