MSH6 and colorectal carcinoma: MMRd arises from either (1) an inherited germline mutation in one of four genes (MLH1, MSH2, MSH6 and PMS2) constituting the DNA MMR system followed by an acquired second hit in the wild-type allele of the same gene in colonic mucosa cells (i.e., Lynch syndrome), or (2) somatic inactivation of the MLH1 gene (i.e., MSI sporadic CRC).