Biclonality of gastric lymphomas

The pathogenesis and clonal evolution of gastric diffuse large B-cell lymph oma (DLBCL) and its relationship to extranodal marginal zone B-cell lymphom a (MZBL), mucosa-associated lymphoid tissue (MALT) type, are still controve rsial. The aim of this study was to establish the clonality of morphologica lly distinct areas of gastric lymphomas as well as their genetic relationsh ip to each other. Six gastric lymphomas, consisting of two MZBL, MALT type, two DLBCL, and two "composite" lymphomas were subjected to laser capture m icrodissection and subsequent PCR-based amplification of the immunoglobulin heavy chain gene. One DLBCL showed a biclonal pattern of rearranged immuno globulin heavy chain (IgH) genes of two different areas without evidence of a common origin. Two composite DLBCL with areas of extranodal MZBL, MALT t ype, were also biclonal and displayed different IgH gene rearrangements in the small-cell and in the large-cell components. respectively. Sequencing o f the CDR3 region revealed unique VH-N-D and D-N-JH junctions, thus corrobo rating the presence of two genuinely distinct tumor clones in each of these three cases. In contrast, the remaining three gastric lymphomas tone DLBCL and two MZBL, MALT type) showed IgH gene rearrangements in which CDR3 regi ons were identical in the different tumor areas. Our results suggest that g astric DLBCL may be composed of more than one tumor cell clone. Further, DL BCL may not necessarily evolve by transformation of a low-grade lymphoma, b ut may also originate de novo. An ongoing emergence of new tumor clones may considerably hamper molecular diagnosis and follow-up of gastric DLBCL.