The epigenetic progenitor origin of human cancer

Andrew P. Feinberg, Rolf Ohlsson, Steven Henikoff

Research output: Contribution to journalReview articlepeer-review

Abstract

Cancer is widely perceived as a heterogeneous group of disorders with markedly different biological properties, which are caused by a series of clonally selected genetic changes in key tumour-suppressor genes and oncogenes. However, recent data suggest that cancer has a fundamentally common basis that is grounded in a polyclonal epigenetic disruption of stem/progenitor cells, mediated by 'tumour-progenitor genes'. Furthermore, tumour cell heterogeneity is due in part to epigenetic variation in progenitor cells, and epigenetic plasticity together with genetic lesions drives tumour progression. This crucial early role for epigenetic alterations in cancer is in addition to epigenetic alterations that can substitute for genetic variation later in tumour progression. Therefore, non-neoplastic but epigenetically disrupted stem/progenitor cells might be a crucial target for cancer risk assessment and chemoprevention.

Original languageEnglish (US)
Pages (from-to)21-33
Number of pages13
JournalNature Reviews Genetics
Volume7
Issue number1
DOIs
StatePublished - Jan 1 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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