MLH1 and hereditary nonpolyposis colon cancer: In contrast to hereditary MSI-H CRC (hereditary non-polyposis colorectal cancer [HNPCC]/Lynch syndrome) in the setting of germline mutations in mismatch repair (MMR) genes17, spontaneous MSI-H CRC is predominantly caused by methylation of the MLH1 promoter and consecutive inactivation of the MLH1 gene18,19.