Biclonality of gastric lymphomas

被引:22
作者
Cabras, AD
Candidus, S
Fend, F
Kremer, M
Schulz, S
Bordi, C
Weirich, G
Höfler, H
Werner, M
机构
[1] GSF, Natl Res Ctr Environm & Hlth, Inst Pathol, Dept Pathol, D-85764 Neuherberg, Germany
[2] Tech Univ Munich, Dept Pathol, D-8000 Munich, Germany
[3] Dept Pathol, Parma, Italy
关键词
D O I
10.1038/labinvest.3780308
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The pathogenesis and clonal evolution of gastric diffuse large B-cell lymphoma (DLBCL) and its relationship to extranodal marginal zone B-cell lymphoma (MZBL), mucosa-associated lymphoid tissue (MALT) type, are still controversial. The aim of this study was to establish the clonality of morphologically distinct areas of gastric lymphomas as well as their genetic relationship to each other. Six gastric lymphomas, consisting of two MZBL, MALT type, two DLBCL, and two "composite" lymphomas were subjected to laser capture microdissection and subsequent PCR-based amplification of the immunoglobulin heavy chain gene. One DLBCL showed a biclonal pattern of rearranged immunoglobulin heavy chain (IgH) genes of two different areas without evidence of a common origin. Two composite DLBCL with areas of extranodal MZBL, MALT type, were also biclonal and displayed different IgH gene rearrangements in the small-cell and in the large-cell components. respectively. Sequencing of the CDR3 region revealed unique VH-N-D and D-N-JH junctions, thus corroborating 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 regions were identical in the different tumor areas. Our results suggest that gastric DLBCL may be composed of more than one tumor cell clone. Further, DLBCL may not necessarily evolve by transformation of a low-grade lymphoma, but may also originate de novo. An ongoing emergence of new tumor clones may considerably hamper molecular diagnosis and follow-up of gastric DLBCL.
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页码:961 / 967
页数:7
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