Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma

被引：268

作者：

Guo, Guangwu ^{[1
]}

Gui, Yaoting ^{[2
]}

Gao, Shengjie ^{[1
]}

Tang, Aifa ^{[2
,3
]}

Hu, Xueda ^{[1
]}

Huang, Yi ^{[2
,3
]}

Jia, Wenlong ^{[1
]}

Li, Zesong ^{[2
,3
]}

He, Minghui ^{[1
]}

Sun, Liang ^{[2
]}

Song, Pengfei ^{[1
]}

Sun, Xiaojuan ^{[3
]}

Zhao, Xiaokun ^{[4
]}

Yang, Sangming ^{[1
]}

Liang, Chaozhao ^{[5
]}

Wan, Shengqing ^{[1
]}

Zhou, Fangjian ^{[6
]}

Chen, Chao ^{[1
]}

Zhu, Jialou ^{[1
,7
]}

Li, Xianxin ^{[2
]}

Jian, Minghan ^{[1
]}

Zhou, Liang ^{[2
]}

Ye, Rui ^{[1
]}

Huang, Peide ^{[1
]}

Chen, Jing ^{[2
]}

Jiang, Tao ^{[1
]}

Liu, Xiao ^{[1
]}

Wang, Yong ^{[2
]}

Zou, Jing ^{[1
]}

Jiang, Zhimao ^{[2
]}

Wu, Renhua ^{[1
]}

Wu, Song ^{[2
]}

Fan, Fan ^{[1
]}

Zhang, Zhongfu ^{[2
]}

Liu, Lin ^{[1
]}

Yang, Ruilin ^{[2
]}

Liu, Xingwang ^{[1
]}

Wu, Haibo ^{[1
]}

Yin, Weihua ^{[2
]}

Zhao, Xia ^{[1
]}

Liu, Yuchen ^{[2
]}

Peng, Huanhuan ^{[1
]}

Jiang, Binghua ^{[2
]}

Feng, Qingxin ^{[2
]}

Li, Cailing ^{[2
]}

Xie, Jun ^{[2
]}

Lu, Jingxiao ^{[2
]}

Kristiansen, Karsten ^{[1
,8
]}

Li, Yingrui ^{[1
]}

Zhang, Xiuqing ^{[1
]}

机构：

[1] BGI Shenzhen, Shenzhen Key Lab Trans Biotechnol, Shenzhen, Peoples R China

[2] Peking Univ, Guangdong & Shenzhen Key Lab Male Reprod Med & Ge, Inst Urol, Shenzhen Hosp,Shenzhen PKU HKUST Med Ctr, Shenzhen, Peoples R China

[3] Shenzhen Univ, Shenzhen Peoples Hosp 2, Affiliated Hosp 1, Shenzhen, Peoples R China

[4] Central So Univ, Xiangya Hosp 2, Dept Urol, Changsha, Peoples R China

[5] Anhui Med Univ, Affiliated Hosp 1, Dept Urol, Hefei, Peoples R China

[6] Sun Yat Sen Univ, Ctr Canc, Dept Urol, Guangzhou 510275, Guangdong, Peoples R China

[7] Wuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China

[8] Univ Copenhagen, Dept Biol, Copenhagen, Denmark

[9] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark

来源：

NATURE GENETICS | 2012年 / 44卷 / 01期

基金：

中国国家自然科学基金;

关键词：

SOMATIC MUTATIONS;

D O I：

10.1038/ng.1014

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We sequenced whole exomes of ten clear cell renal cell carcinomas (ccRCCs) and performed a screen of similar to 1,100 genes in 88 additional ccRCCs, from which we discovered 12 previously unidentified genes mutated at elevated frequencies in ccRCC. Notably, we detected frequent mutations in the ubiquitin-mediated proteolysis pathway (UMPP), and alterations in the UMPP were significantly associated with overexpression of HIF1 alpha and HIF2 alpha in the tumors (P = 0.01 and 0.04, respectively). Our findings highlight the potential contribution of UMPP to ccRCC tumorigenesis through the activation of the hypoxia regulatory network.

引用

页码：17 / 19

页数：3

共 14 条

[1] Genetic and epigenetic analysis of von Hippel-Lindau (VHL) gene alterations and relationship with clinical variables in sporadic renal cancer [J].

Banks, RE ;

Tirukonda, P ;

Taylor, C ;

Hornigold, N ;

Astuti, D ;

Cohen, D ;

Maher, ER ;

Stanley, AJ ;

Harnden, P ;

Joyce, A ;

Knowles, M ;

Selby, PJ .

CANCER RESEARCH, 2006, 66 (04) :2000-2011

[2] Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes [J].

Dalgliesh, Gillian L. ;

Furge, Kyle ;

Greenman, Chris ;

Chen, Lina ;

Bignell, Graham ;

Butler, Adam ;

Davies, Helen ;

Edkins, Sarah ;

Hardy, Claire ;

Latimer, Calli ;

Teague, Jon ;

Andrews, Jenny ;

Barthorpe, Syd ;

Beare, Dave ;

Buck, Gemma ;

Campbell, Peter J. ;

Forbes, Simon ;

Jia, Mingming ;

Jones, David ;

Knott, Henry ;

Kok, Chai Yin ;

Lau, King Wai ;

Leroy, Catherine ;

Lin, Meng-Lay ;

McBride, David J. ;

Maddison, Mark ;

Maguire, Simon ;

McLay, Kirsten ;

Menzies, Andrew ;

Mironenko, Tatiana ;

Mulderrig, Lee ;

Mudie, Laura ;

O'Meara, Sarah ;

Pleasance, Erin ;

Rajasingham, Arjunan ;

Shepherd, Rebecca ;

Smith, Raffaella ;

Stebbings, Lucy ;

Stephens, Philip ;

Tang, Gurpreet ;

Tarpey, Patrick S. ;

Turrell, Kelly ;

Dykema, Karl J. ;

Khoo, Sok Kean ;

Petillo, David ;

Wondergem, Bill ;

Anema, John ;

Kahnoski, Richard J. ;

Teh, Bin Tean ;

Stratton, Michael R. .

NATURE, 2010, 463 (7279) :360-363

[3] Somatic mutations affect key pathways in lung adenocarcinoma [J].

Ding, Li ;

Getz, Gad ;

Wheeler, David A. ;

Mardis, Elaine R. ;

McLellan, Michael D. ;

Cibulskis, Kristian ;

Sougnez, Carrie ;

Greulich, Heidi ;

Muzny, Donna M. ;

Morgan, Margaret B. ;

Fulton, Lucinda ;

Fulton, Robert S. ;

Zhang, Qunyuan ;

Wendl, Michael C. ;

Lawrence, Michael S. ;

Larson, David E. ;

Chen, Ken ;

Dooling, David J. ;

Sabo, Aniko ;

Hawes, Alicia C. ;

Shen, Hua ;

Jhangiani, Shalini N. ;

Lewis, Lora R. ;

Hall, Otis ;

Zhu, Yiming ;

Mathew, Tittu ;

Ren, Yanru ;

Yao, Jiqiang ;

Scherer, Steven E. ;

Clerc, Kerstin ;

Metcalf, Ginger A. ;

Ng, Brian ;

Milosavljevic, Aleksandar ;

Gonzalez-Garay, Manuel L. ;

Osborne, John R. ;

Meyer, Rick ;

Shi, Xiaoqi ;

Tang, Yuzhu ;

Koboldt, Daniel C. ;

Lin, Ling ;

Abbott, Rachel ;

Miner, Tracie L. ;

Pohl, Craig ;

Fewell, Ginger ;

Haipek, Carrie ;

Schmidt, Heather ;

Dunford-Shore, Brian H. ;

Kraja, Aldi ;

Crosby, Seth D. ;

Sawyer, Christopher S. .

NATURE, 2008, 455 (7216) :1069-1075

[4]

Forbes S A, 2008, Curr Protoc Hum Genet, VChapter 10, DOI 10.1002/0471142905.hg1011s57

[5]

Getz G, 2007, SCIENCE, V317, DOI 10.1126/science.1138764

[6] Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder [J].

Gui, Yaoting ;

Guo, Guangwu ;

Huang, Yi ;

Hu, Xueda ;

Tang, Aifa ;

Gao, Shengjie ;

Wu, Renhua ;

Chen, Chao ;

Li, Xianxin ;

Zhou, Liang ;

He, Minghui ;

Li, Zesong ;

Sun, Xiaojuan ;

Jia, Wenlong ;

Chen, Jinnong ;

Yang, Shangming ;

Zhou, Fangjian ;

Zhao, Xiaokun ;

Wan, Shengqing ;

Ye, Rui ;

Liang, Chaozhao ;

Liu, Zhisheng ;

Huang, Peide ;

Liu, Chunxiao ;

Jiang, Hui ;

Wang, Yong ;

Zheng, Hancheng ;

Sun, Liang ;

Liu, Xingwang ;

Jiang, Zhimao ;

Feng, Dafei ;

Chen, Jing ;

Wu, Song ;

Zou, Jing ;

Zhang, Zhongfu ;

Yang, Ruilin ;

Zhao, Jun ;

Xu, Congjie ;

Yin, Weihua ;

Guan, Zhichen ;

Ye, Jiongxian ;

Zhang, Hong ;

Li, Jingxiang ;

Kristiansen, Karsten ;

Nickerson, Michael L. ;

Theodorescu, Dan ;

Li, Yingrui ;

Zhang, Xiuqing ;

Li, Songgang ;

Wang, Jian .

NATURE GENETICS, 2011, 43 (09) :875-878

[7] Frequent Mutation of BAP1 in Metastasizing Uveal Melanomas [J].

Harbour, J. William ;

Onken, Michael D. ;

Roberson, Elisha D. O. ;

Duan, Shenghui ;

Cao, Li ;

Worley, Lori A. ;

Council, M. Laurin ;

Matatall, Katie A. ;

Helms, Cynthia ;

Bowcock, Anne M. .

SCIENCE, 2010, 330 (6009) :1410-1413

[8] The TSC1 tumour suppressor hamartin regulates cell adhesion through ERM proteins and the GTPase Rho [J].

Lamb, RF ;

Roy, C ;

Diefenbach, TJ ;

Vinters, HV ;

Johnson, MW ;

Jay, DG ;

Hall, A .

NATURE CELL BIOLOGY, 2000, 2 (05) :281-287

[9] Molecular Diagnosis and Therapy of Kidney Cancer [J].

Linehan, W. Marston ;

Bratslavsky, Gennady ;

Pinto, Peter A. ;

Schmidt, Laura S. ;

Neckers, Len ;

Bottaro, Donald P. ;

Srinivasan, Ramaprasad .

ANNUAL REVIEW OF MEDICINE, 2010, 61 :329-343

[10] Renal cell carcinoma [J].

Rini, Brian I. ;

Campbell, Steven C. ;

Escudier, Bernard .

LANCET, 2009, 373 (9669) :1119-1132

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