Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Epigenetic stem cell signature in cancer

Abstract

Embryonic stem cells rely on Polycomb group proteins to reversibly repress genes required for differentiation. We report that stem cell Polycomb group targets are up to 12-fold more likely to have cancer-specific promoter DNA hypermethylation than non-targets, supporting a stem cell origin of cancer in which reversible gene repression is replaced by permanent silencing, locking the cell into a perpetual state of self-renewal and thereby predisposing to subsequent malignant transformation.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: PRC2 promoter occupancy in human ES cells and DNA methylation in human colorectal tumors and matched normal mucosa.

Similar content being viewed by others

References

  1. Houghton, J., Morozov, A., Smirnova, I. & Wang, T.C. Semin. Cancer Biol. published online 4 May 2006 (doi:10.1016/j.semcancer.2006.04.003).

  2. Passegue, E. Nature 442, 754–755 (2006).

    Article  CAS  PubMed  Google Scholar 

  3. Pardal, R., Clarke, M.F. & Morrison, S.J. Nat. Rev. Cancer 3, 895–902 (2003).

    Article  CAS  PubMed  Google Scholar 

  4. Jordan, C.T., Guzman, M.L. & Noble, M. N. Engl. J. Med. 355, 1253–1261 (2006).

    Article  CAS  PubMed  Google Scholar 

  5. Ringrose, L. & Paro, R. Annu. Rev. Genet. 38, 413–443 (2004).

    Article  CAS  PubMed  Google Scholar 

  6. Schuebel, K., Chen, W. & Baylin, S.B. Nat. Genet. 38, 738–740 (2006).

    Article  CAS  PubMed  Google Scholar 

  7. Lee, T.I. et al. Cell 125, 301–313 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Weisenberger, D.J. et al. Nat. Genet. 38, 787–793 (2006).

    Article  CAS  PubMed  Google Scholar 

  9. Hatada, I. et al. Oncogene 25, 3059–3064 (2006).

    Article  CAS  PubMed  Google Scholar 

  10. Squazzo, S.L. et al. Genome Res. 16, 890–900 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bracken, A.P., Dietrich, N., Pasini, D., Hansen, K.H. & Helin, K. Genes Dev. 20, 1123–1136 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Feinberg, A.P., Ohlsson, R. & Henikoff, S. Nat. Rev. Genet. 7, 21–33 (2006).

    Article  CAS  PubMed  Google Scholar 

  13. Eads, C.A. et al. Cancer Res. 60, 5021–5026 (2000).

    CAS  PubMed  Google Scholar 

  14. Shen, L. et al. J. Natl. Cancer Inst. 97, 1330–1338 (2005).

    Article  CAS  PubMed  Google Scholar 

  15. Roy, N.S. et al. Nat. Med. 12, 1259–1268 (2006).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The work described in this manuscript was supported by grants from the European Union (FP6-016467; Biognosis) and from the FWF Austrian Science Fund (L69-B05) awarded to M.W. and by US National Institutes of Health grant R01 CA075090 awarded to P.W.L.

Author information

Authors and Affiliations

Authors

Contributions

E.M.-H. and C.M. provided tissue samples. D.E. and G.S. contributed to the hematopoietic stem cell work. H.F., D.J.W. and M.C. performed MethyLight analyses and provided MethyLight reaction details. J.Y. and I.J. provided logistical and intellectual support. M.W. and P.W.L. analyzed the association between PRC2 occupancy and cancer-specific DNA methylation and jointly wrote the manuscript.

Corresponding authors

Correspondence to Martin Widschwendter or Peter W Laird.

Ethics declarations

Competing interests

P.W.L. is a shareholder, consultant and scientific advisory board member of Epigenomics, AG, which has a commercial interest in DNA methylation markers. This work was not supported by Epigenomics, AG.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Widschwendter, M., Fiegl, H., Egle, D. et al. Epigenetic stem cell signature in cancer. Nat Genet 39, 157–158 (2007). https://doi.org/10.1038/ng1941

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng1941

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing