The role of microsatellite instability in gastric low- and high-grade lymphoma development

DNA mismatch repair genes and their dysfunction as evidenced by microsatell ite instability (MSI) play an important role in the pathogenesis of a varie ty of tumors, most prominently heredity nonpolyposis colorectal cancer (HNP CC), However, their role in development of extranodal lymphomas has not bee n established yet. We therefore evaluated for MSI 25 gastric low-grade marg inal-zone B-cell lymphomas of mucosa-associated lymphoid tissue type and 31 gastric high-grade diffuse large B-cell lymphomas (DLBCLs) with 29 and 118 microsatellites, respectively. Compared with HNPCC, the overall level of M SI was much lower with a mean of 2.6% MSI-positive repeats in the DLBCLs; t he frequency of MSI showed a tendency to increase with age (P = 0.01), as d id MSI variability (p = 0.02), Low-grade mucosa-associated lymphoid tissue lymphomas displayed even less MSI (sevenfold) than DLBCLs (P = 0.009), MSI frequency thus in creases with the transition from low- to high-grade disea se and with age; it does not seem to initiate lymphomagenesis. Other micros atellites than those typically mutated in HNPCC frequently revealed P(ISI i n these lymphomas, especially dinucleotide repeats on chromosomes 3, 5, and 18, To facilitate rapid screening of lymphomas for MSI and to establish a tool for future MSI frequency comparisons, we recommend to use repeats D3S1 261, D3S1530, D5S346, D17S250, D18S474,and DCC.