PMS2 Background Information The finding that mutations in DNA mismatch repair genes are associated with hereditary nonpolyposis colorectal cancer (HNPCC) has resulted in considerable interest in the understanding of the mechanism of DNA mismatch repair. Initially, inherited mutations in the MSH2 and MLH1 homologs of the bacterial DNA mismatch repair genes MutS and MutL were demonstrated at high frequency in HNPCC and were shown to be associated with microsatellite instability. The demonstration that 10 to 45% of pancreatic, gastric, breast, ovarian and small cell lung cancers also display microsatellite instability has been interpreted to suggest that DNA mismatch repair is not restricted to HNPCC tumors but is a common feature in tumor initiation or progression. Two additional homologs of the prokaryotic MutL gene, designated PMS1 and PMS2, have been identified and shown to be mutated in the germline of HNPCC patients.
