MLH1 and hereditary nonpolyposis colon cancer: Dysfunction of the mismatch repair (MMR) system is either caused by germline mutational inactivation of genes encoding MMR proteins, most commonly MLH1, MSH2, and MSH6 in HNPCC patients or by epigenetic silencing of the promoter region of MMR genes, predominantly MLH1, by CpG island hypermethylation.