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Identification of functional cooperative mutations of SETD2 in human acute leukemia

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收录情况： ◇ SCIE ◇ 自然指数

作者：
Zhu, Xiaofan[1,2,3,4] * ; He, Fuhong[5] ; Zeng, Huimin[1,2,3,4] ; Ling, Shaoping[5] ; Chen, Aili[5,6,7,8,9] ; Wang, Yaqin[1,2,3,4] ; Yan, Xiaomei[6,7,8] ; Wei, Wei[1,2,3,4] ; Pang, Yakun[1,2,3,4] ; Cheng, Hui[1,2,3,4] ; Hua, Chunlan[1,2,3,4] ; Zhang, Yue[1,2,3,4,6,7,8] ; Yang, Xuejing[5,9] ; Lu, Xin[5,9] ; Cao, Lihua[5] ; Hao, Lingtong[5] ; Dong, Lili[5] ; Zou, Wei[5] ; Wu, Jun[5] ; Li, Xia[5,9] ; Zheng, Si[5,9] ; Yan, Jin[5] ; Zhou, Jing[5] ; Zhang, Lixia[5,9] ; Mi, Shuangli[5] ; Wang, Xiaojuan[1,2,3,4] ; Zhang, Li[1,2,3,4] ; Zou, Yao[1,2,3,4] ; Chen, Yumei[1,2,3,4] ; Geng, Zhe[10] ; Wang, Jianmin[11] ; Zhou, Jianfeng[10] ; Liu, Xin[12,13] ; Wang, Jianxiang[1,2,3,4] ; Yuan, Weiping[1,2,3,4] ; Huang, Gang[6,7,8] ; Cheng, Tao[1,2,3,4] ; Wang, Qian-fei[5] ;
单位： [1]Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin, Peoples R China; [2]Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China; [3]Chinese Acad Med Sci, Ctr Stem Cell Med, Tianjin, Peoples R China; [4]Peking Union Med Coll, Tianjin, Peoples R China; [5]Chinese Acad Sci, Beijing Inst Genom, Lab Genome Variat & Precis Biomed, Beijing, Peoples R China; [6]Cincinnati Childrens Hosp Med Ctr, Div Pathol, Cincinnati, OH 45229 USA; [7]Cincinnati Childrens Hosp Med Ctr, Div Pathol, Cincinnati, OH 45229 USA; [8]Cincinnati Childrens Hosp, Div Canc Biol, Cincinnati, OH USA; [9]Univ Chinese Acad Sci, Beijing, Peoples R China; [10]Huazhong Univ Sci & Technol, TongJi Med Coll, TongJi Hosp, Dept Hematol, Wuhan 430074, Hubei, Peoples R China; [11]Second Mil Med Univ, Changhai Hosp, Dept Hematol, Shanghai, Peoples R China; [12]Ann & Robert H Lurie Childrens Hosp, Chicago Res Ctr, Mary Ann & J Milburn Smith Child Hlth Res Program, Chicago, IL USA; [13]Northwestern Univ, Dept Pediat, Feinberg Sch Med, Chicago, IL 60611 USA
出处：
DOI： 10.1038/ng.2894
ISSN：

摘要：
Acute leukemia characterized by chromosomal rearrangements requires additional molecular disruptions to develop into full-blown malignancy(1,2), yet the cooperative mechanisms remain elusive. Using whole-genome sequencing of a pair of monozygotic twins discordant for MLL (also called KMT2A) gene-rearranged leukemia, we identified a transforming MLL-NRIP3 fusion gene(3) and biallelic mutations in SETD2 (encoding a histone H3K36 methyltransferase)(4). Moreover, loss-of-function point mutations in SETD2 were recurrent (6.2%) in 241 patients with acute leukemia and were associated with multiple major chromosomal aberrations. We observed a global loss of H3K36 trimethylation (H3K36me3) in leukemic blasts with mutations in SETD2. In the presence of a genetic lesion, downregulation of SETD2 contributed to both initiation and progression during leukemia development by promoting the self-renewal potential of leukemia stem cells. Therefore, our study provides compelling evidence for SETD2 as a new tumor suppressor. Disruption of the SETD2-H3K36me3 pathway is a distinct epigenetic mechanism for leukemia development.

基金：
China Ministry of Science and TechnologyMinistry of Science and Technology, China [2011CB964801, 2012CB966600, 2010DFB30270, 2014CB542001]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81090411, 81130074, 30825017, 81000220, 81070442, 91331111]; Hundred Talents Program of the Chinese Academy of SciencesChinese Academy of Sciences; Tianjin Municipal Science and Technology Commission [09ZCZDSF03800]; 'Strategic Priority Research Program' of the Chinese Academy of SciencesChinese Academy of Sciences [XDA01010305]; 'Knowledge Innovation Program' of the Chinese Academy of SciencesChinese Academy of SciencesKnowledge Innovation Program of the Chinese Academy of Sciences; Pilot Research Grant of the State Key Laboratory of Experimental Hematology; Leukemia and Lymphoma SocietyLeukemia and Lymphoma Society [1027-08]; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [P30DK090971, P30DK090971, P30DK090971, P30DK090971, P30DK090971, P30DK090971, P30DK090971, P30DK090971, P30DK090971, P30DK090971] Funding Source: NIH RePORTER

基金编号： 2011CB964801 2012CB966600 2010DFB30270 2014CB542001 81090411 81130074 30825017 81000220 81070442 91331111 09ZCZDSF03800 XDA01010305 1027-08 P30DK090971

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外文
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中科院(CAS)分区：
出版当年[2013]版：
大类 | 1 区 生物
小类 | 1 区 遗传学
最新[2025]版：
大类 | 1 区 生物学
小类 | 1 区 遗传学
JCR分区：
出版当年[2012]版：
Q1 GENETICS & HEREDITY
最新[2024]版：
Q1 GENETICS & HEREDITY

影响因子： 最新[2024版] 最新五年平均 出版当年[2012版] 出版当年五年平均 出版前一年[2011版] 出版后一年[2013版]

第一作者：
第一作者单位： [1]Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin, Peoples R China; [2]Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China; [3]Chinese Acad Med Sci, Ctr Stem Cell Med, Tianjin, Peoples R China; [4]Peking Union Med Coll, Tianjin, Peoples R China;
通讯作者：
通讯机构： [1]Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin, Peoples R China; [2]Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China; [3]Chinese Acad Med Sci, Ctr Stem Cell Med, Tianjin, Peoples R China; [4]Peking Union Med Coll, Tianjin, Peoples R China;
推荐引用方式(GB/T 7714)：
Zhu Xiaofan,He Fuhong,Zeng Huimin,et al.Identification of functional cooperative mutations of SETD2 in human acute leukemia[J].NATURE GENETICS.2014,46(3):287-+.doi:10.1038/ng.2894.
APA：
Zhu, Xiaofan,He, Fuhong,Zeng, Huimin,Ling, Shaoping,Chen, Aili...&Wang, Qian-fei.(2014).Identification of functional cooperative mutations of SETD2 in human acute leukemia.NATURE GENETICS,46,(3)
MLA：
Zhu, Xiaofan,et al."Identification of functional cooperative mutations of SETD2 in human acute leukemia".NATURE GENETICS 46..3(2014):287-+

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