Mutational analysis of the 5 ' noncoding region of the bcl-6 gene in primary gastric lymphomas

Bcl-6 mRNA and protein are frequently expressed in the transformed counterp arts of the germinal center B-cells, diffuse large B-cell lymphoma and foll icular lymphoma, irrespective of the gene rearrangements. Most of the prima ry gastric lymphomas are thought to be of mucosa-associated lymphoid tissue (MALT) origin, and neither bcl-6 gene rearrangement nor protein expression is found in low-grade gastric lymphomas of the MALT type as in normal marg inal zone cells. However, bcl-6 protein expression was identified in high-g rade gastric lymphomas, suggesting its role in high-grade transformation. I n this study, polymerase chain reaction-single strand conformation polymorp hism (PCR-SSCP) analysis for bcl-6 primer was performed in order to ascerta in the molecular mechanisms of bcl-6 protein expression in primary gastric lymphomas, A total 31 cases of gastric lymphoma were classified into low-gr ade gastric lymphomas of MALT type (n = 13), high-grade gastric lymphomas o f MALT type (n = 6) and gastric diffuse large B-cell lymphomas (n = 12). Bc l-6 mutations were observed in 11 of 13 (84.6%) low-grade gastric lymphomas of the MALT type and in 8 of 12 (66.7%) diffuse large B-cell gastric lymph omas, In 6 cases of the high-grade gastric lymphomas of the MALT type, both the low- and high-grade components demonstrated the same frequency (3/6, 5 0%) of mutations,The tissue obtained from the marginal zone of Peyer's patc h by microdissection technique revealed no bcl-6 mutations by the PCR-SSCP analysis. These findings suggest that the acquisition process of bcl-6 muta tions by the marginal zone cells may be involved in the lymphomagenesis of the stomach, but our data does not explain the reason why bcl-6 protein is expressed only in high-grade gastric lymphomas.