Epigenetic gene silencing in cancer - a mechanism for early oncogenic pathway addiction?

Nat Rev Cancer. 2006 Feb;6(2):107-16. doi: 10.1038/nrc1799.


Chromatin alterations have been associated with all stages of tumour formation and progression. The best characterized are epigenetically mediated transcriptional-silencing events that are associated with increases in DNA methylation - particularly at promoter regions of genes that regulate important cell functions. Recent evidence indicates that epigenetic changes might 'addict' cancer cells to altered signal-transduction pathways during the early stages of tumour development. Dependence on these pathways for cell proliferation or survival allows them to acquire genetic mutations in the same pathways, providing the cell with selective advantages that promote tumour progression. Strategies to reverse epigenetic gene silencing might therefore be useful in cancer prevention and therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Cell Proliferation
  • Cell Survival
  • Cell Transformation, Neoplastic / genetics*
  • DNA Methylation
  • Epigenesis, Genetic*
  • Gene Silencing*
  • Humans
  • Neoplasms / genetics
  • Neoplasms / physiopathology
  • Promoter Regions, Genetic
  • Signal Transduction