Genetic study of gastric lymphoma : somatic mutation analysis of VH genes for lymphomagenesis and blastic transformation

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To clarify the cell characteristics and origins of low-grade MALT-type lymphoma (L-MALT) and high-grade lesion (H-L), and to investigate the clonal relationships among these tumors, we compared histologic, immunohistologic, and genetic characteristics of L-MALT, H-L, and diffuse large B-cell lymphoma (DLBCL). Our analysis revealed the following results.1) From data obtained by somatic mutation analysis, L-MALT is thought to originate from post-germinal center B-cells that have undergone antigen selection. The ongoing mutation of L-MALT may reflect reentry into a germinal center pathway.2) Extranodal DLBCL has a higher somatic mutation frequency, exhibiting antigen-driven high affinity, than that of nodal DLBCL.3) Histologic and immunohistologic differences were found in L-MALT, H-L, and DLBCL.4) The frequently mutated VH genes of H-L and DLBCL suggest that these lymphomas may be driven from germinal center or post-germinal center B-cells.5) The PCR analysis of CDR3 and VH regions of L-MALT and H-L in a successful case revealed different nucleic acid sequences, suggesting that L-MALT and H-L may represent unrelated clones.Further investigation using single-cell PCR will determine any clonal link and prognostic significance between H-L and DLBCL arising from mucosa-associated lymphoid tissues.