Intratumoral Heterogeneity of the Epigenome

Cancer Cell. 2016 Apr 11;29(4):440-451. doi: 10.1016/j.ccell.2016.03.009.


Investigation into intratumoral heterogeneity (ITH) of the epigenome is in a formative stage. The patterns of tumor evolution inferred from epigenetic ITH and genetic ITH are remarkably similar, suggesting widespread co-dependency of these disparate mechanisms. The biological and clinical relevance of epigenetic ITH are becoming more apparent. Rare tumor cells with unique and reversible epigenetic states may drive drug resistance, and the degree of epigenetic ITH at diagnosis may predict patient outcome. This perspective presents these current concepts and clinical implications of epigenetic ITH, and the experimental and computational techniques at the forefront of ITH exploration.

Publication types

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

MeSH terms

  • Cell Transformation, Neoplastic / genetics*
  • CpG Islands / genetics
  • DNA Methylation
  • DNA, Neoplasm / chemistry
  • DNA, Neoplasm / genetics
  • Disease Progression
  • Epigenesis, Genetic*
  • Epigenomics*
  • Forecasting
  • Gene Expression Regulation, Neoplastic*
  • Genetic Heterogeneity*
  • Humans
  • Mutation
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Neoplastic Stem Cells / metabolism
  • Promoter Regions, Genetic / genetics


  • DNA, Neoplasm