DNA-mismatch repair (MMR) is an essential process in maintaining genetic stability. Lack of a functional DNA-mismatch repair pathway is a common characteristic of several different types of human cancers, either due to an MMR gene mutation or promoter methylation gene silencing. MLH1 is an integral part of the protein complex responsible for mismatch repair and is expressed in lymphocytes, heart, colon, breast, lung, spleen, testis, prostate, thyroid and gall bladder tissues, and is methylated in several ovarian tumors. Loss of MLH1 protein expression is associated with a mutated phenotype, microsatellite instability and a predisposition to cancer. In hereditary nonpolyposis colorectal cancer (HNPCC), an autosomal dominant inherited cancer syndrome that signifies a high risk of colorectal and various other types of cancer, the MLH1 gene exhibits a pathogenic mutation. Certain cancer cell lines, including leukemia CCRF-CEM, colon HCT 116 and KM12, and ovarian cancers SK-OV-3 and IGROV-1, show complete deficiency of MLH1, while MLH1 is expressed in 60% of melanomas, 70% of noninvasive squamous cell carcinomas and 30% of invasive squamous cell carcinomas.
