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学科主题基础医学
A20, ABIN-1/2, and CARD11 Mutations and Their Prognostic Value in Gastrointestinal Diffuse Large B-Cell Lymphoma
Dong, Gehong1,2; Chanudet, Estelle1; Zeng, Naiyan1; Appert, Alex1; Chen, Yun-Wen3; Au, Wing-Yan4; Hamoudi, Rifat A.1; Watkins, A. James1; Ye, Hongtao1; Liu, Hongxiang1; Gao, Zifen2; Chuang, Shih-Sung5,6; Srivastava, Gopesh3; Du, Ming-Qing1
刊名CLINICAL CANCER RESEARCH
2011-03-15
DOI10.1158/1078-0432.CCR-10-1859
17期:6页:1440-1451
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
资助者Leukemia and Lymphoma Research, UK ; Elimination of Leukemia Fund, UK ; Lady Tata Memorial Trust ; Kay Kendal Leukemia Fund, UK ; China Scholarship Council ; Leukemia and Lymphoma Research, UK ; Elimination of Leukemia Fund, UK ; Lady Tata Memorial Trust ; Kay Kendal Leukemia Fund, UK ; China Scholarship Council
研究领域[WOS]Oncology
关键词[WOS]NF-KAPPA-B ; SYSTEMIC-LUPUS-ERYTHEMATOSUS ; CHINESE HAN POPULATION ; GASTRIC MALT LYMPHOMA ; HODGKIN LYMPHOMA ; A20-BINDING INHIBITOR ; MULTIPLE-MYELOMA ; TARGET-GENE ; TNFAIP3 A20 ; ASSOCIATION
英文摘要

Purpose: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of aggressive lymphomas with the activated B-cell-like subtype characterized by constitutive NF-kappa B activation. Activating mutations of CARD11 and inactivating mutations of A20 are frequent events in DLBCL. However, the full extent of genetic alterations in the NF-kappa B pathway regulators and their potential prognostic value in DLBCL remain to be investigated. We investigated the genetic abnormalities of CARD11, A20, and ABIN-1/2/3 (the A20 binding inhibitor of NF-kappa B) and their clinicopathologic correlation in gastrointestinal DLBCL.

Experimental Design: The somatic mutation and copy number changes of CARD11, A20, and ABIN-1/2/3 were investigated in 71 gastrointestinal DLBCLs by PCR/sequencing, and interphase FISH/array comparative genomic hybridization, respectively. The mutations identified were functionally characterized by NF-kappa B reporter assays and immunoprecipitation experiments.

Results: Recurrent somatic mutations were found in CARD11 (10%), A20 (17%), ABIN-1 (4%), and ABIN-2 (3%), but not in ABIN-3. In comparison with the wild-type, all CARD11 mutants were potent NF-kappa B activators in vitro. On the basis of the destructive nature of the observed mutations, and the findings by reporter assays and immunoprecipitation studies, most if not all of the somatic mutations that were seen in A20, ABIN-1, and ABIN-2 could impair their normal functions. Among these genetic abnormalities, A20 somatic mutation was significantly associated with both poor overall survival and event-free survival.

Conclusions: We show further evidence of NF-kappa B pathway genetic abnormalities in DLBCL, which are potentially valuable in the prognosis and design of future therapeutic strategies. Clin Cancer Res; 17(6); 1440-51. (C)2011 AACR.

语种英语
资助者Leukemia and Lymphoma Research, UK ; Elimination of Leukemia Fund, UK ; Lady Tata Memorial Trust ; Kay Kendal Leukemia Fund, UK ; China Scholarship Council ; Leukemia and Lymphoma Research, UK ; Elimination of Leukemia Fund, UK ; Lady Tata Memorial Trust ; Kay Kendal Leukemia Fund, UK ; China Scholarship Council
WOS记录号WOS:000288435300024
引用统计
被引频次:36[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/60278
专题基础医学院_病理学系
作者单位1.Taipei Med Univ, Taipei, Taiwan
2.Chi Mei Med Ctr, Dept Pathol, Tainan, Taiwan
3.Univ Cambridge, Dept Pathol, Div Mol Histopathol, Cambridge CB2 0QQ, England
4.Beijing Univ, Hlth Sci Ctr, Dept Pathol, Beijing 100871, Peoples R China
5.Univ Hong Kong, Queen Mary Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China
6.Univ Hong Kong, Queen Mary Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China
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GB/T 7714
Dong, Gehong,Chanudet, Estelle,Zeng, Naiyan,et al. A20, ABIN-1/2, and CARD11 Mutations and Their Prognostic Value in Gastrointestinal Diffuse Large B-Cell Lymphoma[J]. CLINICAL CANCER RESEARCH,2011,17(6):1440-1451.
APA Dong, Gehong.,Chanudet, Estelle.,Zeng, Naiyan.,Appert, Alex.,Chen, Yun-Wen.,...&Du, Ming-Qing.(2011).A20, ABIN-1/2, and CARD11 Mutations and Their Prognostic Value in Gastrointestinal Diffuse Large B-Cell Lymphoma.CLINICAL CANCER RESEARCH,17(6),1440-1451.
MLA Dong, Gehong,et al."A20, ABIN-1/2, and CARD11 Mutations and Their Prognostic Value in Gastrointestinal Diffuse Large B-Cell Lymphoma".CLINICAL CANCER RESEARCH 17.6(2011):1440-1451.
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