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Nat Rev Cancer. 2013 Jul;13(7):497-510. doi: 10.1038/nrc3486. Epub 2013 Jun 13.

Cancer as a dysregulated epigenome allowing cellular growth advantage at the expense of the host.

Author information

1
Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

Abstract

Although at the genetic level cancer is caused by diverse mutations, epigenetic modifications are characteristic of all cancers, from apparently normal precursor tissue to advanced metastatic disease, and these epigenetic modifications drive tumour cell heterogeneity. We propose a unifying model of cancer in which epigenetic dysregulation allows rapid selection for tumour cell survival at the expense of the host. Mechanisms involve both genetic mutations and epigenetic modifications that disrupt the function of genes that regulate the epigenome itself. Several exciting recent discoveries also point to a genome-scale disruption of the epigenome that involves large blocks of DNA hypomethylation, mutations of epigenetic modifier genes and alterations of heterochromatin in cancer (including large organized chromatin lysine modifications (LOCKs) and lamin-associated domains (LADs)), all of which increase epigenetic and gene expression plasticity. Our model suggests a new approach to cancer diagnosis and therapy that focuses on epigenetic dysregulation and has great potential for risk detection and chemoprevention.

PMID:
23760024
PMCID:
PMC4636434
DOI:
10.1038/nrc3486
[Indexed for MEDLINE]
Free PMC Article

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