TY - JOUR
T1 - The epigenetic progenitor origin of human cancer
AU - Feinberg, Andrew P.
AU - Ohlsson, Rolf
AU - Henikoff, Steven
N1 - Funding Information:
146. Hu M, et al. Distinct epigenetic changes in the stromal cells of breast cancers. Nature Genet. 37, 899–905 (2005). Acknowledgements We thank A. Gondor, P. Onyango, S. Petersen-Mahrt, B. Vogelstein, H. Bjornsson and C. Iacobuzio-Donahue for helpful comments. This article is largely focused on the idea of early epigenetic events in stem cells before tumours are apparent. For this reason we have referred the reader to several excellent reviews for detailed discussions of later events in tumorigenesis, and apologize to authors whose work we were unable to discuss owing to space limitations. Work discussed here was supported by a US National Institutes of Health grant to A.F.
PY - 2006/1
Y1 - 2006/1
N2 - 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.
AB - 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.
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U2 - 10.1038/nrg1748
DO - 10.1038/nrg1748
M3 - Review article
C2 - 16369569
AN - SCOPUS:29244469466
SN - 1471-0056
VL - 7
SP - 21
EP - 33
JO - Nature Reviews Genetics
JF - Nature Reviews Genetics
IS - 1
ER -