Send to:

Choose Destination
See comment in PubMed Commons below
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

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


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.

Copyright © 2013 Elsevier Inc. All rights reserved.

[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk