肿瘤SDH基因突变的研究进展

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肿瘤SDH基因突变的研究进展
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作者单位:浙江理工大学生命科学学院，浙江省家蚕生物反应器和生物医药重点实验室,浙江理工大学生命科学学院，浙江省家蚕生物反应器和生物医药重点实验室,浙江清华长三角研究院，浙江省应用酶学重点实验室,浙江理工大学生命科学学院，浙江省家蚕生物反应器和生物医药重点实验室;浙江清华长三角研究院，浙江省应用酶学重点实验室
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基金项目:浙江省重大科技专项(2012C03007-4)，浙江省嘉兴市科技计划项目(2014AY21021)，浙江省高校生物学重中之重一级学科浙江理工大学科研启动基金(14042107-Y)资助

Advances of Succinate Dehydrogenase Mutation in Cancers

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Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Zhejiang Sci-Tech University,Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Zhejiang Sci-Tech University,Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University,Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Zhejiang Sci-Tech University，Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University

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This work was supported by grants from Zhejiang Provincial Top Key Discipline of Biology, Science Foundation of Zhejiang Sci-Tech University (14042107-Y), the Major Science and Technology Special Project of Zhejiang Province (2012C03007-4, 2014C03004), Science and Technology Bureau of Jiaxing (2014AY21021), China

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线粒体琥珀酸脱氢酶(succinate dehydrogenase，SDH)是三羧酸循环和有氧电子传递呼吸链中的关键酶之一，包含A、B、C、D 4个亚基．4个亚基分别由4个基因编码，即SDHA、SDHB、SDHC和SDHD，4个基因突变可以诱发癌症，包括副神经节瘤(paraganglioma，PGL)、嗜铬细胞瘤(pheochromocytoma，PHEO)、肾细胞癌(renal cell carcinoma，RCC)、胃肠道间质瘤(gastrointestinal stromal tumors，GIST)、Leigh综合症等．近年来，突变的SDH已经被证实是一种重要的诊断与预后的生物标志物和治疗分子标靶．本文就SDH存在的各种突变以及在肿瘤发生、发展与转移的作用机理研究的进展进行全面的论述．

Abstract:

Succinate dehydrogenase(SDH), a cruciral multiprotein enzymatic complex in the Krebs cycle/transport chain, is located in the cristate of the mitochondria, and composed of A, B, C, and D subunits, which are encoded by SDHA, SDHB, SDHC, and SDHD, respectively. The SDH mutations play a crucial oncogenic role in paraganglioma (PGL, types 1-5), pheochromocytoma (PHEO), renal cell carcinoma (RCC), gastrointestinal stromal tumors (GIST), rare hypophyseal adenomas, and Leigh syndromes. Mutated SDH has been proved to be an important biomarker for diagnosis and a therapeutic target in these cancers. This review summarized and updated a variety of SDH mutations in the neoplasms and discussed the oncogenic role of SDH mutants in proliferation, apoptosis, invasion, migration, tumorgenesis and senescence.

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曹智发,陈伟才,杨佩佩,周海梦,欧文斌.肿瘤SDH基因突变的研究进展[J].生物化学与生物物理进展,2017,44(1):31-43

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收稿日期:2016-08-18
最后修改日期:2016-12-01
接受日期:2016-12-02
在线发布日期: 2017-01-17
出版日期: 2017-01-20

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