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Classically, colorectal cancer (CRC) has been believed to develop from normal mucosa through the premalignant adenoma by the step-wise accumulation of mutations. All CRC display either microsatellite instability (MSI) or chromosome instability (CIN). MSI occurs in 15% of colon cancers and results from inactivation of the DNA mismatch repair (MMR) system by either MMR gene mutations or hypermethylation of the MLH1 promoter. MSI promotes tumorigenesis through generating mutations in target genes that possess coding microsatellite repeats, such as beta-catenin, TGFBR2 and BAX. CIN is found in the majority of colon cancers and leads to a different pattern of gene alterations that contribute to tumor formation. Genes involved in CIN are those coding for APC, K-ras, SMAD4 and p53. |
Colorectal cancer - Reference pathway
