MSH2 and Lynch syndrome: Lynch syndrome (LS) is an autosomal dominant cancer predisposition syndrome caused by germline pathogenic variants (PVs) affecting one of four mismatch repair (MMR) genes: MLH1, MSH2, MSH6, and PMS2. These PVs include germline 3’ deletions in the EPCAM gene that lead to hypermethylation of surrounding DNA, including the downstream promoter of MSH2 causing MSH2 silencing.