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Brief Communication

Nature Genetics 39, 157–158 (1 February 2007) | doi:10.1038/ng1941

Epigenetic stem cell signature in cancer

Martin Widschwendter , Heidi Fiegl , Daniel Egle , Elisabeth Mueller-Holzner , Gilbert Spizzo , Christian Marth , Daniel J Weisenberger , Mihaela Campan , Joanne Young , Ian Jacobs & Peter W Laird

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.