2.5. Epigenetics, stem cells and cancer

Principles of stem cell biology and cancer: future applications and therapeutics. Edited by T. Regad, T. J. Sayers and R. C. Rees. John Wiley & Sons (2015)

Part I. Stem Cells


Although malignant transformation has typically been associated with mutations and translocations, aberrant patterns of histone and DNA modification can also account for driver events in tumorigenesis. Altered expression and mutation of chromatin modifiers have been largely described in tumours (Rodriguez-Paredes and Esteller, 2011). The fact that DNA methyltransferases and histone deacetylases inhibitors are successfully used to treat cancer shows the relevance of the epigenetic machinery in this process (Esteller, 2008). Moreover, cancer-dependent epigenetic signatures can be reverted during reprogramming to pluripotency, highlighting the reversibility of aberrant epigenetic marks (Ron-Bigger et al., 2010).

Several studies have proposed potential links between chromatin features in ESCs and cancer cells. Promoters marked with bivalent domains in ESCs, which are commonly DNA hypomethylated in both ESCs and differentiated cells, have a tendency to become hypermethylated in cancer (Widschwendter et al., 2007; Doi et al., 2009). The acquisition of DNA methylation at bivalent genes in self-renewing adult stem cells can impair their induction during differentiation and lock stem cells in an immature proliferating state (Trowbridge et al., 2012). Similarly, activating mutations of Ezh2 found in transformed B cells can lead to aberrant silencing of bivalent differentiation genes, with similar consequences (Bйguelin et al., 2013).

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