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学科主题: 基础医学
题名:
A20, ABIN-1/2, and CARD11 Mutations and Their Prognostic Value in Gastrointestinal Diffuse Large B-Cell Lymphoma
作者: 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
发表日期: 2011-03-15
DOI: 10.1158/1078-0432.CCR-10-1859
卷: 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
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
项目资助者: Leukemia and Lymphoma Research, UK ; Elimination of Leukemia Fund, UK ; Lady Tata Memorial Trust ; Kay Kendal Leukemia Fund, UK ; China Scholarship Council
WOS记录号: WOS:000288435300024
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60278
Appears in Collections:基础医学院_病理学系_期刊论文

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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

Recommended Citation:
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.
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