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

为了明确低度恶性MALT型淋巴瘤(L-MALT)和高度恶性病变(H-L)的细胞特征和起源，探讨两者之间的克隆关系，我们比较了L-MALT、H-L和弥漫性大B细胞淋巴瘤的组织学、免疫组织学和遗传学特征。我们的分析结果如下：1)从体细胞突变分析的数据来看，L-MALT可能来源于生发中心后的B细胞，经过抗原选择。L-MALT的持续突变可能反映了其重新进入生发中心的途径。2)结外DLBCL的体细胞突变频率高于结外DLBC，表现出抗原驱动的高亲和力。4)在组织学和免疫组织学上发现L-MALT、H-L和DLBCL存在差异。4)H-L和DLBCL的VH基因频繁突变提示这些淋巴瘤可能来自生发中心或生发后中心B细胞。5)对L-MALT和H-L CDR3和VH区的聚合酶链式反应分析显示，在一个成功的病例中，提示L-MALT和H-L可能是不相关的克隆，单细胞聚合酶链式反应的进一步研究将确定H-L与粘膜相关淋巴组织来源的DLBCL之间是否存在克隆性联系及其预后意义。

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.