Histone H3.3 mutations: a variant path to cancer

Cancer Cell. 2013 Nov 11;24(5):567-74. doi: 10.1016/j.ccr.2013.09.015.


A host of cancer types exhibit aberrant histone modifications. Recently, distinct and recurrent mutations in a specific histone variant, histone H3.3, have been implicated in a high proportion of malignant pediatric brain cancers. The presence of mutant H3.3 histone disrupts epigenetic posttranslational modifications near genes involved in cancer processes and in brain function. Here, we review possible mechanisms by which mutant H3.3 histones may act to promote tumorigenesis. Furthermore, we discuss how perturbations in normal H3.3 chromatin-related and epigenetic functions may more broadly contribute to the formation of human cancers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carcinogenesis / genetics*
  • Epigenesis, Genetic
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics*
  • Glioma / metabolism
  • Histones / genetics*
  • Histones / metabolism
  • Humans
  • Mutation, Missense


  • Histones