Somatic hypermutation signature in B-cell low-grade lymphomas
Somatic hypermutation signature in B-cell low-grade lymphomas
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DOI：
10.3324/haematol.12999
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发表时间：
2008-08-01
期刊：
影响因子：
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通讯作者：
Piris, Miguel A.
中科院分区：
文献类型：
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作者：
Tracey, Lorraine;Aggarwal, Mohit;Piris, Miguel A.
背景免疫球蛋白基因体细胞高突变是不同类型的低度恶性B细胞淋巴瘤，包括慢性淋巴细胞白血病、套细胞淋巴瘤和脾边缘区淋巴瘤的生物学相关和临床有用的预后因子。对93例小B-淋巴瘤患者的IgV（H）突变状态和表达谱进行了联合研究。ResultsThe分析确定了参与基因转录，DNA修复和复制，染色体维护的调控基因的体细胞高突变签名。这些基因中的8个进行了蛋白质分析，使用组织微阵列，为一组118例。我们发现了RAD 51 C和CDK 7蛋白表达与体细胞超突变状态之间的明确联系，因为任一标志物的阳性表达与突变状态显著相关（p < 0.003）。我们还发现TFDP 1和POLA的阳性表达与正在进行的体细胞高突变显著相关（p < 0.001）。为了评估这些体细胞超突变标记物的潜在临床应用性，我们研究了一系列包含在组织微阵列中的套细胞淋巴瘤病例。RCC 1和CDK 7的表达，单独和一起，被认为是显着相关的较长的总survival. ConclusionsA体细胞高突变签名已被确定为不同类型的小B细胞淋巴瘤。这具有潜在的机理和诊断价值。
BackgroundImmunoglobulin gene somatic hypermutation is a biologically relevant and clinically useful prognostic factor in different types of low-grade B-cell lymphomas, including chronic lymphocytic leukemia, mantle cell lymphoma and splenic marginal zone lymphoma.Design and MethodsWith the aim of identifying surrogate markers of somatic hypermutation, a combined investigation of IgV(H) mutational status and expression profiles of 93 samples from patients with small B-cell lymphoma was performed.ResultsThe analysis identified an somatic hypermutation signature of genes involved in the regulation of gene transcription, DNA repair and replication, and chromosome maintenance. Eight of these genes were subjected to protein analysis using tissue microarrays, for a set of 118 cases. We found a clear link between RAD51C and CDK7 protein expression and somatic hypermutation status, in that positive expression of either marker was significantly associated with a mutated status (p < 0.003). We also found that positive expression of TFDP1 and POLA was significantly associated with ongoing somatic hypermutation (p < 0.001). To assess the potential clinical applicability of these somatic hypermutation markers, we studied a series of cases of mantle cell lymphoma included in a tissue microarray. The expression of RCC1 and CDK7, separately and together, was found to be significantly associated with longer overall survival.ConclusionsAn somatic hypermutation signature has been identified for different types of small B-cell lymphoma. This has a potential mechanistic and diagnostic value.