title: Epigenetic events in the colorectum and in colon cancer.
abstract: Colon cancers arise from benign neoplasms and evolve into adenocarcinomas through a stepwise histological progression sequence, proceeding from either adenomas or hyperplastic polyps/serrated adenomas. Genetic alterations have been associated with specific steps in this polyp-adenocarcinoma sequence and are believed to drive the histological progression of colon cancer. Recently, epigenetic alterations, which include CGI (CpG island) DNA methylation, have been shown to occur in colon polyps and colon cancer. The aberrant methylation of genes appears to co-operate with the genetic alterations to drive the initiation and progression of colon polyps to colon cancer. CGI DNA methylation is an epigenetic mechanism that represses gene transcription in normal cellular processes, but it becomes excessive and aberrant in many neoplasms. The aberrant DNA methylation affects CpG-rich regions, called CGIs, in the 5' region of genes and results in transcriptional silencing through effects on transcription factor binding and associated changes in chromatin structure. These hypermethylated genes are not only probable pathogenic events affecting colon-cancer formation, but also neoplasm-specific molecular events that may be useful as molecular markers for colon tumours. Furthermore, aberrant DNA methylation of tumour-suppressor genes may occur secondary to a genetic predisposition or to a field-cancerization effect in the colon and may be useful as molecular markers for the risk of developing colon cancer.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. wgrady@fhcrc.org
authors.forename: W M
authors.initials: WM
authors.lastname: Grady
mesh_terms: D003106:Colon / Q000502:physiology*; D003110:Colonic Neoplasms / Q000235:genetics*; D003111:Colonic Polyps / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics*; D020868:Gene Silencing; D005819:Genetic Markers; D006801:Humans; D012007:Rectum / Q000502:physiology*
chemical_list: D005819:Genetic Markers