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CIMP and colon cancer gets more complicated
  1. William M Grady
  1. Clinical Research Division, Fred Hutchinson Cancer Research Center; Department of Medicine, University of Washington Medical School; R&D Service, VA Puget Sound Health Care System, Seattle, WA
  1. William M Grady, Fred Hutchinson Cancer Research Center 1100 Fairview Ave N. D4–100, Seattle, WA 98109; wgrady{at}fhcrc.org

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Evidence for a subset of colon cancers with low-level CIMP that has unique molecular and clinical features compared with cancers with no CIMP and high-level CIMP

Colorectal cancer (CRC) is one of the most commonly occurring cancers in adults, and arises through the cumulative effects of inherited genetic susceptibilities and environmental exposures. These two sets of factors interact to cause CRC by either inducing or permitting the progressive accumulation of gene mutations (such as those in APC, the “gatekeeper” tumour suppressor gene) and alterations to the epigenome (such as aberrant methylation of MGMT or CDKN2A). The importance of the accumulation of multiple gene mutations in causing colon cancer is highlighted by the fact that colon cancer can be divided at the molecular level into at least two distinct molecular categories based on the types of mutations observed. These two categories are the chromosome instability (CIN) group, which is characterised by the presence of aneuploidy, chromosome translocations, and chromosomal gains and losses, and the microsatellite instability (MSI) group, which is characterised by the presence of frameshift mutations in repetitive elements of DNA called microsatellite repeats. These molecular subgroups of tumours have different mutation frequencies for certain genes such as TP53 and BRAF, and have unique clinical features, such as the tendency of MSI tumours to occur in the right side of the colon and to have less aggressive clinical behaviour than CIN tumours.1

Recently, considerable attention has also been focused on the role of epigenetic alterations of candidate tumour suppressor genes in the molecular pathogenesis of CRC. It is well known that the expression of genes can be affected by gene-promoter methylation and the chromatin structure of the gene locus, which are epigenetic factors that regulate gene expression. In particular, the aberrant methylation of CpG island DNA in …

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