High BCL6 expression predicts better prognosis, independent of BCL6 translocation status, translocation partner, or BCL6-deregulating mutations, in gastric lymphoma
High BCL6 expression predicts better prognosis, independent of BCL6 translocation status, translocation partner, or BCL6-deregulating mutations, in gastric lymphoma
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DOI：
10.1182/blood-2006-05-022517
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发表时间：
2006-10-01
期刊：
影响因子：
20.3
通讯作者：
Srivastava, Gopesh
中科院分区：
文献类型：
--
作者：
Chen, Yun-Wen;Hu, Xiao-Tong;Srivastava, Gopesh
为了研究 BCL6 在胃淋巴瘤发病机制中的作用，我们分析了 43 例胃淋巴瘤中 BCL6 启动子区域的 BCL6 反位、体细胞高突变和失调突变，其中包括 4 例粘膜相关淋巴组织的结外边缘区 B 细胞淋巴瘤（MALT 淋巴瘤）、33 例弥漫性大 B 细胞淋巴瘤（DLBCL）和 6 例伴有残留 MALT 淋巴瘤的复合 DLBCL （DLCLML）。 BCL6 启动子被免疫球蛋白 (Ig) 和非 Ig、易位伴侣取代，导致其失调，经常与 DLBCL (36.4%) 和 DLCLML (50%) 有关。还鉴定了两个新的 BCL6 易位伴侣基因：28S rRNA 和 DMRT1，以及内含子 2 中的一个新的 BCL6 易位断点。仅在 DLBCL (24.2%) 中发现了失调突变，这与 BCL6 蛋白的高表达显着相关。值得注意的是，BCL6 高表达与较长的总生存期 (OS) 密切相关，与胃 DLBCL 和 DLCLML 的机制无关。免疫组织化学将胃 DLBCL 进一步细分为生发中心 B 细胞样 (GCB) 和非 GCB 亚组。无论 BCL6 基因改变如何，在所有 GCB 病例中均检测到 BCL6 高表达。在非 GCB 亚组中，BCL6 失调突变与 BCL6 高表达水平显着相关。非GCB亚组中BCL6表达水平与OS无显着相关性，其预后明显差于GCB亚组。
To investigate the role of BCL6 in the pathogenesis of gastric lymphoma, we analyzed the BCL6 promoter region for BCL6 trans locations, somatic hypermutations, and deregulating mutations in 43 gastric lymphomas, including 4 extranodal marginal-zone B-cell lymphomas of mucosa-associated lymphoid tissues (MALT lymphomas), 33 diffuse large B-cell lymphomas (DLBCLs), and 6 composite DLBCLs with residual MALT lymphoma (DLCLMLs). BCL6 promoter substitutions by immunoglobulin (Ig) and non-Ig, translocation partners, resulting in its deregulation, were frequently involved in DLBCL (36.4%) and DLCLML (50%). Two novel BCL6 translocation partner genes, 28S rRNA and DMRT1, and a new BCL6 translocation breakpoint in intron 2 were also identified. Deregulating mutations were found only in DLBCL (24.2%), which correlated significantly with high BCL6 protein expression. Significantly, high BCL6 expression correlated strongly with longer overall survival (OS), independent of mechanism in gastric DLBCL and DLCLML. Gastric DLBCLs were further subclassified into germinal center B-cell-like (GCB) and non-GCB subgroups immunohistochemically. High BCL6 expression was detected in all GCB cases, irrespective of BCL6 genetic alterations. In the non-GCB subgroup, BCL6-deregulating mutations correlated significantly with high BCL6 expression level. No significant correlation was found between the BCL6 expression level and OS in the non-GCB subgroup, which had significantly poorer prognosis than the GCB subgroup.