Epigenetic alterations in colorectal cancer: the CpG island methylator phenotype

Abstract

DNA methylation is one of the key mechanisms of epigenetic modification, and genome-wide hypomethylation and CpG island hypermethylation are characteristics of cancer cells. The CpG island methylator phenotype (CIMP) is a distinctive subtype of colorectal cancers (CRCs) that show concordant hypermethylation of numerous promoter CpG island loci. CIMP-positive CRCs are associated with a proximal location in the colon, microsatellite instability, BRAF mutation and a relatively poor clinical outcome. CIMP-positive CRCs have their own precursor lesions, serrated adenomas, distinct from conventional adenomas which progress and transform into CIMP-negative CRCs. Although the existence of CIMP-positive CRCs is generally accepted, there has been controversy over technical issues with gene markers, the methodology used to define CIMP, and the prognostic or predictive role of CIMP. This review addresses recent advances in the field of CIMP-related research.