MLH1 and Lynch syndrome: 10%–15% of CRCs display genomic instability due to DNA mismatch repair deficiency (MMRd), caused by germline mutation of mismatch repair (MMR) genes MLH1, MSH2, MSH6, or PMS2 (Lynch syndrome),2 biallelic somatic mutation of MMR genes,3,4 or, more commonly, somatic silencing of MLH1 by promoter methylation.5