Splenic marginal zone lymphoma:: proposal of new diagnostic and prognostic markers identified after tissue and cDNA microarray analysis
Splenic marginal zone lymphoma:: proposal of new diagnostic and prognostic markers identified after tissue and cDNA microarray analysis
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DOI：
10.1182/blood-2004-10-3898
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发表时间：
2005-09-01
期刊：
影响因子：
20.3
通讯作者：
Piris, MA
中科院分区：
文献类型：
--
作者：
Ruiz-Ballesteros, E;Mollejo, M;Piris, MA
脾边缘区淋巴瘤是一种新发现的淋巴瘤类型，其确切的分子发病机制尚不清楚。这妨碍了与其他小B细胞恶性肿瘤的鉴别诊断。为了更全面地描述这种肿瘤的特征，并确定新的诊断和预后标志物，我们在一个相对较大的44个SMZL系列中进行了cDNA微阵列表达谱分析和组织微阵列（TMA）免疫组化研究。结果与免疫球蛋白重链可变区（IgV（H））突变状态和临床结局相关。SMZL显示出很大程度上同质的特征，这意味着单个分子实体的存在。在SMZL中失调的基因中，可以特别提及涉及B细胞受体（BCR）信号传导、肿瘤坏死因子（TNF）信号传导和核因子-κ B（NF-κ B）活化的基因，例如SYK、BTK、BIRC 3、TRAF 3和LTB。观察到的其他基因是SELL和LPXN，它们在脾脏中高度表达，以及淋巴瘤癌基因，如ARHH和TCL 1。相反，位于7 q31（一个常见的缺失区域）的基因CAV 1、CAV 2和GNG 11在整个系列中下调。与包含其他小B细胞淋巴瘤特征的基因进行比较，鉴定了3个基因，其表达区分SMZL，即ILF 1、SENA TAXIN和CD 40。较短的生存期与CD 38表达、初始IgV（H）基因和一组NF-κ B通路基因（包括TRAF 5、REL和PKCA）的表达相关。
Splenic marginal zone lymphoma (SMZL) is a newly recognized lymphoma type whose precise molecular pathogenesis is still essentially unknown. This hampers differential diagnosis with other small B-cell malignancies. With the aim of characterizing this tumor more comprehensively, and of identifying new diagnostic and prognostic markers, we performed cDNA microarray expression profiling and tissue microarray (TMA) immunohistochemical studies in a relatively large series of 44 SMZLs. The results were related to immunoglobulin heavy chain variable region (IgV(H)) mutational status and clinical outcome. SMZLs display a largely homogenous signature, implying the existence of a single molecular entity. Of the genes deregulated in SMZLs, special mention may be made of the genes involved in B-cell receptor (BCR) signaling, tumor necrosis factor (TNF) signaling and nuclear factor-kappa B (NF-kappa B) activation, such as SYK, BTK, BIRC3, TRAF3, and LTB. Other genes observed were SELL and LPXN, which were highly expressed in spleen, and lymphoma oncogenes, such as ARHH and TCL1. In contrast, the genes CAV1, CAV2, and GNG11 located in 7q31, a commonly deleted area, were downregulated in the entire series. A comparison with the genes comprising the signature of other small B-cell lymphomas identified 3 genes whose expression distinguishes SMZL, namely ILF1, SENA TAXIN, and CD40. Shorter survival was associated with CD38 expression, naive IgV(H) genes, and the expression of a set of NF-kappa B pathway genes, including TRAF5, REL, and PKCA.