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

被引：271

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
Banks, RE
Tirukonda, P
Taylor, C
Hornigold, N
Astuti, D
Cohen, D
Maher, ER
Stanley, AJ
Harnden, P
Joyce, A
Knowles, M
Selby, PJ
[J]. CANCER RESEARCH, 2006, 66 (04) : 2000 - 2011
[2] Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes
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.
[J]. NATURE, 2010, 463 (7279) : 360 - 363
[3] Somatic mutations affect key pathways in lung adenocarcinoma
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.
[J]. 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
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
[J]. NATURE GENETICS, 2011, 43 (09) : 875 - 878
[7] Frequent Mutation of BAP1 in Metastasizing Uveal Melanomas
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.
[J]. SCIENCE, 2010, 330 (6009) : 1410 - 1413
[8] The TSC1 tumour suppressor hamartin regulates cell adhesion through ERM proteins and the GTPase Rho
Lamb, RF
Roy, C
Diefenbach, TJ
Vinters, HV
Johnson, MW
Jay, DG
Hall, A
[J]. NATURE CELL BIOLOGY, 2000, 2 (05) : 281 - 287
[9] Molecular Diagnosis and Therapy of Kidney Cancer
Linehan, W. Marston
Bratslavsky, Gennady
Pinto, Peter A.
Schmidt, Laura S.
Neckers, Len
Bottaro, Donald P.
Srinivasan, Ramaprasad
[J]. ANNUAL REVIEW OF MEDICINE, 2010, 61 : 329 - 343
[10] Renal cell carcinoma
Rini, Brian I.
Campbell, Steven C.
Escudier, Bernard
[J]. LANCET, 2009, 373 (9669) : 1119 - 1132

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