Nature Reviews Genetics 7, 21-33 (January 2006) | doi:10.1038/nrg1748

The epigenetic progenitor origin of human cancer

Andrew P. Feinberg1, Rolf Ohlsson2 & Steven Henikoff3  About the authors


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.

Author affiliations

  1. Departments of Medicine, Oncology, and Molecular Biology and Genetics, 1064 Ross Building, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, Maryland 21205, USA.
  2. Department of Development and Genetics, Uppsala University, Uppsala, Sweden.
  3. Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.

Correspondence to: Andrew P. Feinberg1 Email:


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