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