Molecular genetics of colorectal cancer

Colorectal cancer is the end result of an accumulation of destabilizing mutations and other genetic events, which occur in clones of colonocytes over many years. While each colorectal cancer is genetically unique, there are at least three distinct mechanisms by which the process occurs. The commonest is chromosomal instability, producing microsatellite stable, aneuploid cancers. The second is DNA promoter methylation that underlies CpG island methylation phenotype cancers, either microsatellite stable or unstable, and the third is loss of DNA mismatch repair, causing microsatellite unstable, diploid cancers. Cancers arising from these three mechanisms are biologically different and the differences have clinical implications.