Translocations involving the immunoglobulin heavy chain gene locus predict better survival in gastric diffuse large B-cell lymphoma
Translocations involving the immunoglobulin heavy chain gene locus predict better survival in gastric diffuse large B-cell lymphoma
复制标题
DOI：
10.1158/1078-0432.ccr-07-4946
复制
发表时间：
2008-05-15
影响因子：
11.5
通讯作者：
Du, Ming-Qing
中科院分区：
文献类型：
--
作者：
Nakamura, Shotaro;Ye, Hongtao;Du, Ming-Qing
目的：胃弥漫性大b细胞淋巴瘤（DLBCL）的发病机制和临床异质性尚不清楚。我们全面调查了胃癌DLBCL中淋巴瘤相关染色体易位的发生率和临床意义，特别是涉及免疫球蛋白重链（IGH）基因位点的染色体易位。实验设计：纳入141例原发性胃DLBCL[伴有粘膜相关淋巴组织（MALT）淋巴瘤58例，无MALT淋巴瘤83例]。利用间期荧光原位杂交技术研究了涉及BCL6、c-MYC、FOXP1、MALT1和IGH的易位。在阳性病例中，用适当的探针对潜在的伴侣基因进行额外的荧光原位杂交。通过CD10、13CL6和MUM1的免疫表型分析，将病例分为生发中心b细胞样（GCB）或非GCB亚组。结果：111例患者中有36例（32%）检出IGH易位；他们的伴侣基因包括BCL6 (n = 10), c-MYC （n = 5）和FOXP1 (n = 3)，但在其余18例中仍然未知。t(14;18)/IGH-BCL2、t(14;18)/IGH-MALT1、t(1;14)/BCL10-IGH均未检出。t(11;18)/AP12-MALT1除1例合并MALT淋巴瘤的DLBCL仅在MALT淋巴瘤细胞中检测到阳性信号外，其余病例均未检测到。高伴位易位与年轻相关，但与包括GCB或非GCB免疫表型在内的任何其他临床病理因素无关。Cox多因素分析显示，除了年龄更小和早期阶段外，与igh相关的易位是总体和efs更好的独立预后因素。结论：胃大bcl中高伴位易位是常见的，并且预后良好。
Purpose: The pathogenesis and clinical heterogeneity of gastric diffuse large B-cell lymphoma (DLBCL) are poorly understood. We have comprehensively investigated the incidence and clinical significance of lymphoma-associated chromosomal translocations, particularly those involving the immunoglobulin heavy chain (IGH) gene locus, in a large series of gastric DLBCL.Experimental Design: One hundred forty-one cases of primary gastric DLBCL [58 with mucosa-associated lymphoid tissue (MALT) lymphoma and 83 without MALT lymphoma] were enrolled. Translocations involving BCL6, c-MYC, FOXP1, MALT1, and IGH were investigated using interphase fluorescence in situ hybridization. In positive cases, additional fluorescence in situ hybridization was done with appropriate probes for potential partner genes. Cases were classified into germinal center B-cell-like (GCB) or non-GCB subgroups by immunophenotyping with CD10, 13CL6, and MUM1.Results: Translocations involving IGH were detected in 36 (32%) of 111 cases; their partner genes included BCL6 (n = 10), c-MYC (n = 5), and FOXP1 (n = 3) but remained unknown in the remaining 18 cases. t(14;18)/IGH-BCL2, t(14;18)/IGH-MALT1, and t(1;14)/BCL10-IGH were not detected in any case. t(11;18)/AP12-MALT1 was detected in none of the cases, except for one case of DLBCL with MALT lymphoma, which showed positive signals only in MALT lymphoma cells. IGH-involved translocation was associated with younger age but not with any other clinicopathologic factors including GCB or non-GCB immunophenotypes. Cox multivariate analysis revealed that IGH-involved translocation, in addition to younger age and early stage, was an independent prognostic factor for better overall and EFSs.Conclusion: IGH-involved translocations are frequent in gastric DLBCL and seem to identify cases with favorable prognosis.