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Epigenetic stem cell signature in cancer

Nature Genetics volume 39, pages 157–158 (2007)Cite this article

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.

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

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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.

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Authors and Affiliations

  1. Department of Gynecological Oncology, Institute for Women's Health, University College London, London, WC1E 6DH, UK

    Martin Widschwendter, Heidi Fiegl & Ian Jacobs

  2. Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck, Austria

    Heidi Fiegl, Daniel Egle, Elisabeth Mueller-Holzner & Christian Marth

  3. Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria

    Gilbert Spizzo

  4. Departments of Surgery and of Biochemistry and Molecular Biology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA

    Daniel J Weisenberger, Mihaela Campan & Peter W Laird

  5. Molecular Cancer Epidemiology Laboratory, Queensland Institute for Medical Research, Herston, 4006, Australia

    Joanne Young

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  1. Martin Widschwendter
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  2. Heidi Fiegl
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  7. Daniel J Weisenberger
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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.

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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.

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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

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