Epigenetic stem cell signature in cancer.
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.
Widschwendter
Martin
M
Department of Gynecological Oncology, Institute for Women's Health, University College London, London WC1E 6DH, UK. M.Widschwendter@ucl.ac.uk
Fiegl
Heidi
H
Egle
Daniel
D
Mueller-Holzner
Elisabeth
E
Spizzo
Gilbert
G
Marth
Christian
C
Weisenberger
Daniel J
DJ
Campan
Mihaela
M
Young
Joanne
J
Jacobs
Ian
I
Laird
Peter W
PW
D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins / Q000502:physiology; D013234:Stem Cells / Q000502:physiology*
D063146:Polycomb-Group Proteins; D012097:Repressor Proteins