Gastric Cancer and DNA Mismatch Repair

Kim, Jae J; Park, Dong Il

Abstract

Cancer developes when mutations accumulate in key growth-regulating genes. The two classes of genes implicated in this malignant transformation are designated oncogenes and tumor-suppressor genes. Recently, a new class of tumor-susceptibility gene which results in a generalized defect in the processes of DNA mismatch repair has been identified. Most patient with hereditary non-polyposis colorectal cancer (HNPCC) syndromes exhibit a mutator phenotype characterized by widespread alterations in the length of repetitive DNA sequences, which is microsatellite instability (MSI). A defect in one or more of the known DNA mismatch repair genes results in the disruption of an enzyme system that maintains the integrity of repetitive sequences which are usually stably inherited. Germline mutations in hMLH1, hMSH2, hPMS1, hPMS2, and possibly hMSH6 may account for over 90% of cases of HNPCC. The literature from the East and West concerning the role of DNA mismatch repair system in gastric carcinoma is conflicting and confusing. It is essential to determine whether DNA mismatch repair system and microsatellite instability in gastric carcinoma are clinically important or purely of academic interest.