MSH6 and colorectal cancer: The remaining 15% of colorectal cancers develop through an alternative pathway of colon cancerogenesis, involving a defective mismatch repair system, due to the inactivation of genes such as MLH1, MLH3, MSH2, MSH3, MSH6, PMS1, PMS2, determining a high rate of somatic mutations (hypermutation) and microsatellite instability; these tumors are also characterized by a high CIMP (CIMPhigh), determining the hypermethylation of some genes, such as MLH1, involved in tumor development.