Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch Syndrome, is an autosomal dominant condition associated with increased risk of multiple cancers particularly colorectal and endometrial. This syndrome most commonly results from mutations of genes encoding DNA mismatch repair proteins including MLH1, MSH2, MSH6 and PMS2. These mutations lead to tumors with microsatellite instability (MSI) – a change in length of a microsatellite allele due to either insertion or deletion of repeating units. MSI can also occur in sporadic colorectal, endometrial and other cancers in patients without HNPCC. In sporadic cancers, MSI is typically associated with silenced MLH1 protein expression resulting from somatic hypermethylation of the MLH1 promoter. However, constitutional epimutations that result in germline MLH1 promoter hypermethylation also exist. Germline MLH1 promoter hypermethylation may confer an HNPCC (Lynch) syndrome phenotype even in the absence of primary sequence alternations in the MLH1 gene. Germline MLH1 promoter methylation can be documented by detecting methylation in non-neoplastic tissue (peripheral blood). Genetic counseling may be indicated based on the clinical and laboratory findings

Please note this “Germline MLH1 Promoter Methylation” test is a distinct orderable and has a different indication than the standard “MLH1 Promoter Methylation” test. The Germline MLH1 Promoter Methylation test is used to evaluate for constitutional MLH1 promoter methylation in peripheral blood specimens. The standard MLH1 Promoter Methylation test is used to evaluate for MLH1 promoter methylation in tumor specimens from formalin-fixed paraffin-embedded tissue blocks.