04.24.06

Methylation “suburbs” implicated in colorectal cancer

Posted in cancer, research articles at 2:35 pm by admin

Nature Genetics has published ahead of print a research article providing new insight into the role that epigenetics plays in the aetiology of colorectal cancer. A research group led by Dr. Susan J. Clark of Garvan Institute of Medical Research in Australia have correlated the global gene suppression of chromosome 2q.14.2, spanning four Mb, in humans with methylation of CpG island “suburbs.”

DNA hypermethylation within the repressed genomic neighborhood was localized to three separate enriched CpG island ’suburbs’, with the largest hypermethylated suburb spanning 1 Mb. These data change our understanding of epigenetic gene silencing in cancer cells: namely, epigenetic silencing can span large regions of the chromosome, and both DNA-methylated and neighboring unmethylated genes can be coordinately suppressed by global changes in histone modification. We propose that loss of gene expression can occur through long-range epigenetic silencing, with similar implications as loss of heterozygosity in cancer.

The authors have also proposed, in connection with their research findings, that the term “suburbs” be used to describe the chromosome “neighborhood” that is implicated in an epigenetic mechanism; that is, a chromosome neighborhood can be divided into a suburb with methylated DNA and a suburb with unmethylated DNA.

This research is important because it potentially means that increased DNA methylation in much larger areas than previously thought could be important in the mechanism leading to the development of colorectal cancer, and potentially other cancers as well. Link