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Cancer Cell. 2013 Jan 14;23(1):9-22. doi: 10.1016/j.ccr.2012.11.006. Epub 2012 Dec 13.

Regional activation of the cancer genome by long-range epigenetic remodeling.

Author information

1
Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.

Abstract

Epigenetic gene deregulation in cancer commonly occurs through chromatin repression and promoter hypermethylation of tumor-associated genes. However, the mechanism underpinning epigenetic-based gene activation in carcinogenesis is still poorly understood. Here, we identify a mechanism of domain gene deregulation through coordinated long-range epigenetic activation (LREA) of regions that typically span 1 Mb and harbor key oncogenes, microRNAs, and cancer biomarker genes. Gene promoters within LREA domains are characterized by a gain of active chromatin marks and a loss of repressive marks. Notably, although promoter hypomethylation is uncommon, we show that extensive DNA hypermethylation of CpG islands or "CpG-island borders" is strongly related to cancer-specific gene activation or differential promoter usage. These findings have wide ramifications for cancer diagnosis, progression, and epigenetic-based gene therapies.

PMID:
23245995
DOI:
10.1016/j.ccr.2012.11.006
[Indexed for MEDLINE]
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