[Genetics and molecular classification of colorectal cancer].
BACKGROUND
Colorectal cancer is a genetic disease for which the adenoma-carcinoma-sequence has served as a teaching model. This article presents an update on carcinogenesis and classification, according to the increased understanding of precursors and the improved insight into molecular biological mechanisms.


METHODS
Literature from 1.1 2002 to 15.7 2007 was reviewed from PubMed by using the search words "colorectal cancer" matched with MeSH-terms "genetic instability", "epigenetic", "molecular classification", "crypt", "apoptosis", "proliferation" and "carcinogenesis". Focus is based on recent reviews (including systematic reviews), and selected original papers.


CONCLUSIONS
Colorectal cancer develops in the stem cells of the crypts through deregulated molecular mechanisms such as the Wnt-pathway, which lead to increased proliferation, lack of differentiation and loss of apoptosis. Precursors, such as the aberrant crypt foci, have potential as early biomarkers, but consensus lacks for their clinical utility. Assumed "innocent" polyps, such as serrated adenomas, appear to play a larger role than previously expected, mainly through epigenetics (CpG Island Methylator Phenotype; CIMP) and microsatellite instability (MSI). Three main pathways occur in the colorectal carcinogenesis (chromosomal instability [CIN] , MSI and CIMP), of which CIN represents the major part. These pathways have distinct clinical, pathological, and genetic characteristics, which can be used for molecular classification for improved diagnostics, prognosis and treatment.
Søreide
Kjetil
K
Avdeling for patologi, Stavanger universitetssjukehus, Postboks 8100, 4068 Stavanger. ksoreide@mac.com
D000236:Adenoma / Q000145:classification / Q000235:genetics / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis; D002277:Carcinoma / Q000145:classification / Q000235:genetics / Q000473:pathology; D003111:Colonic Polyps / Q000473:pathology; D015179:Colorectal Neoplasms / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D044127:Epigenesis, Genetic; D042822:Genomic Instability; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology
D014408:Biomarkers, Tumor