Ongoing somatic mutations and clonal expansions after cure of Helicobacterpylori infection in gastric mucosa-associated lymphoid tissue B-cell lymphoma

Purpose: Although most patients with primary gastric low-grade mucosa-assoc iated lymphoid tissue (MALT) B-cell lymphoma experience complete endoscopic and histologic remission after the cure of Helicobacter pylori infection, in many patients, the polymerase chain reaction (PCR) still detects monoclo nal B cells in the gastric mucosa. The present study asked whether the lymp homa immunoglobulin V-H (IgV(H)) sequences remained stable in patients with gastric MALT lymphoma after H pylori eradication. Patients and Methods: Eight patients with stage El disease treated with H p ylori eradication were analyzed before and at different time points after t he cure of the infection. After the amplification of IgVH genes from DNA ex tracted from gastric biopsy specimens, monoclonal PCR products were cloned and multiple clones (43 to 105)were sequenced per patient. Results: Mutations were detected in all lymphoma VH sequences, which sugges ted germinal center or post-germinal center origin of the lymphoma B cells. In five of the eight patients, clonal heterogeneity was observed at diagno sis or during follow-vp. Genealogical analysis of shared and unshared mutat ions showed that the process of somatic mutations was ongoing after H pylor i eradication in four of the five patients who showed clonal instability. O ngoing mutations were observed in three of the four patients who completely responded to H pylori eradication, but in only one of the four patients wh o did not respond or who partially responded. Conclusion: In low-grade gastric MALT lymphomas, an ongoing process of soma tic hypermutation and antigen selection can be detected after the therapeut ic removal of the underlying stimulus H pylori. These data point to the rel evance of yet unknown antigens that drive this disease. In addition, they c hallenge the view that these lymphomas may be cured solely by the eradicati on of H pylori. (C) 1998 by American Society of Clinical Oncology.