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Nat Rev Genet. 2016 May;17(5):284-99. doi: 10.1038/nrg.2016.13. Epub 2016 Mar 14.

Epigenetic modulators, modifiers and mediators in cancer aetiology and progression.

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Center for Epigenetics, Johns Hopkins University School of Medicine, 855 N. Wolfe Street, Rangos 570, Baltimore, Maryland 21205, USA.
Department of Microbiology, Tumour and Cell Biology, Nobels väg 16, Karolinska Institutet, S-171 77 Stockholm, Sweden.


This year is the tenth anniversary of the publication in this journal of a model suggesting the existence of 'tumour progenitor genes'. These genes are epigenetically disrupted at the earliest stages of malignancies, even before mutations, and thus cause altered differentiation throughout tumour evolution. The past decade of discovery in cancer epigenetics has revealed a number of similarities between cancer genes and stem cell reprogramming genes, widespread mutations in epigenetic regulators, and the part played by chromatin structure in cellular plasticity in both development and cancer. In the light of these discoveries, we suggest here a framework for cancer epigenetics involving three types of genes: 'epigenetic mediators', corresponding to the tumour progenitor genes suggested earlier; 'epigenetic modifiers' of the mediators, which are frequently mutated in cancer; and 'epigenetic modulators' upstream of the modifiers, which are responsive to changes in the cellular environment and often linked to the nuclear architecture. We suggest that this classification is helpful in framing new diagnostic and therapeutic approaches to cancer.

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