癌症中的表观遗传干细胞特征。

Epigenetic stem cell signature in cancer.

作者信息

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

机构信息

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

出版信息

Nat Genet. 2007 Feb;39(2):157-8. doi: 10.1038/ng1941. Epub 2006 Dec 31.

DOI:10.1038/ng1941

PMID:17200673

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.

摘要

胚胎干细胞依靠多梳蛋白家族来可逆地抑制分化所需的基因。我们报告称，与非靶点相比，干细胞多梳蛋白家族的靶点出现癌症特异性启动子DNA高甲基化的可能性高达12倍，这支持了癌症的干细胞起源学说，即在此过程中，可逆的基因抑制被永久沉默所取代，从而使细胞锁定在持续的自我更新状态，进而易发生后续的恶性转化。