MSH6 and Lynch syndrome: About 15% of all CRC cases display MSI-H phenotype, which is caused by the germline mutations of MMR genes, including MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), and PMS1 homolog 2 (PMS2) in Lynch syndrome cases (1–3%) [4,5,6,7,8,9] or somatic hypermethylation of CpG islands surrounding the promoter region of MLH1 in sporadic MSI-H cases (3–15%) [10,11].