The epigenetic progenitor origin of human cancer

Andrew P. Feinberg; Rolf Ohlsson; Steven Henikoff

doi:10.1038/nrg1748

The epigenetic progenitor origin of human cancer

Andrew P. Feinberg, Rolf Ohlsson, Steven Henikoff

School of Medicine

Research output: Contribution to journal › Review article › peer-review

1334 Scopus citations

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 language	English (US)
Pages (from-to)	21-33
Number of pages	13
Journal	Nature Reviews Genetics
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/nrg1748
State	Published - Jan 2006

ASJC Scopus subject areas

Molecular Biology
Genetics
Genetics(clinical)

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title = "The epigenetic progenitor origin of human cancer",

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.",

author = "Feinberg, {Andrew P.} and Rolf Ohlsson and Steven Henikoff",

note = "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.",

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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

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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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The epigenetic progenitor origin of human cancer

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ASJC Scopus subject areas

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