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

Guangwu Guo; Yaoting Gui; Shengjie Gao; Aifa Tang; Xueda Hu; Yi Huang; Wenlong Jia; Zesong Li; Minghui He; Liang Sun; Pengfei Song; Xiaojuan Sun; Xiaokun Zhao; Sangming Yang; Chaozhao Liang; Shengqing Wan; Fangjian Zhou; Chao Chen; Jialou Zhu; Xianxin Li; Minghan Jian; Liang Zhou; Rui Ye; Peide Huang; Jing Chen; Tao Jiang; Xiao Liu; Yong Wang; Jing Zou; Zhimao Jiang; Renhua Wu; Song Wu; Fan Fan; Zhongfu Zhang; Lin Liu; Ruilin Yang; Xingwang Liu; Haibo Wu; Weihua Yin; Xia Zhao; Yuchen Liu; Huanhuan Peng; Binghua Jiang; Qingxin Feng; Cailing Li; Jun Xie; Jingxiao Lu; Karsten Kristiansen; Yingrui Li; Xiuqing Zhang; Songgang Li; Jian Wang; Huanming Yang; Zhiming Cai; Jun Wang

doi:10.1038/ng.1014

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

Guangwu Guo, Yaoting Gui, Shengjie Gao, Aifa Tang, Xueda Hu, Yi Huang, Wenlong Jia, Zesong Li, Minghui He, Liang Sun, Pengfei Song, Xiaojuan Sun, Xiaokun Zhao, Sangming Yang, Chaozhao Liang, Shengqing Wan, Fangjian Zhou, Chao Chen, Jialou Zhu, Xianxin LiMinghan Jian, Liang Zhou, Rui Ye, Peide Huang, Jing Chen, Tao Jiang, Xiao Liu, Yong Wang, Jing Zou, Zhimao Jiang, Renhua Wu, Song Wu, Fan Fan, Zhongfu Zhang, Lin Liu, Ruilin Yang, Xingwang Liu, Haibo Wu, Weihua Yin, Xia Zhao, Yuchen Liu, Huanhuan Peng, Binghua Jiang, Qingxin Feng, Cailing Li, Jun Xie, Jingxiao Lu, Karsten Kristiansen, Yingrui Li, Xiuqing Zhang, Songgang Li, Jian Wang, Huanming Yang, Zhiming Cai, Jun Wang

Biologisk Institut

224 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Nature Genetics
Vol/bind	44
Udgave nummer	1
Sider (fra-til)	17-19
Antal sider	3
ISSN	1061-4036
DOI	https://doi.org/10.1038/ng.1014
Status	Udgivet - jan. 2012

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SOMATIC MUTATIONS
CANCER
Genetics & Heredity

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Guo, G., Gui, Y., Gao, S., Tang, A., Hu, X., Huang, Y., Jia, W., Li, Z., He, M., Sun, L., Song, P., Sun, X., Zhao, X., Yang, S., Liang, C., Wan, S., Zhou, F., Chen, C., Zhu, J., ... Wang, J. (2012). Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma. Nature Genetics, 44(1), 17-19. https://doi.org/10.1038/ng.1014

Guo, G, Gui, Y, Gao, S, Tang, A, Hu, X, Huang, Y, Jia, W, Li, Z, He, M, Sun, L, Song, P, Sun, X, Zhao, X, Yang, S, Liang, C, Wan, S, Zhou, F, Chen, C, Zhu, J, Li, X, Jian, M, Zhou, L, Ye, R, Huang, P, Chen, J, Jiang, T, Liu, X, Wang, Y, Zou, J, Jiang, Z, Wu, R, Wu, S, Fan, F, Zhang, Z, Liu, L, Yang, R, Liu, X, Wu, H, Yin, W, Zhao, X, Liu, Y, Peng, H, Jiang, B, Feng, Q, Li, C, Xie, J, Lu, J, Kristiansen, K, Li, Y, Zhang, X, Li, S, Wang, J, Yang, H, Cai, Z & Wang, J 2012, 'Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma', Nature Genetics, bind 44, nr. 1, s. 17-19. https://doi.org/10.1038/ng.1014

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

abstract = "We sequenced whole exomes of ten clear cell renal cell carcinomas (ccRCCs) and performed a screen of ∼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 HIF1α and HIF2α 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.",

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author = "Guangwu Guo and Yaoting Gui and Shengjie Gao and Aifa Tang and Xueda Hu and Yi Huang and Wenlong Jia and Zesong Li and Minghui He and Liang Sun and Pengfei Song and Xiaojuan Sun and Xiaokun Zhao and Sangming Yang and Chaozhao Liang and Shengqing Wan and Fangjian Zhou and Chao Chen and Jialou Zhu and Xianxin Li and Minghan Jian and Liang Zhou and Rui Ye and Peide Huang and Jing Chen and Tao Jiang and Xiao Liu and Yong Wang and Jing Zou and Zhimao Jiang and Renhua Wu and Song Wu and Fan Fan and Zhongfu Zhang and Lin Liu and Ruilin Yang and Xingwang Liu and Haibo Wu and Weihua Yin and Xia Zhao and Yuchen Liu and Huanhuan Peng and Binghua Jiang and Qingxin Feng and Cailing Li and Jun Xie and Jingxiao Lu and Karsten Kristiansen and Yingrui Li and Xiuqing Zhang and Songgang Li and Jian Wang and Huanming Yang and Zhiming Cai and Jun Wang",

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month = jan,

doi = "10.1038/ng.1014",

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AU - Gui, Yaoting

AU - Gao, Shengjie

AU - Tang, Aifa

AU - Hu, Xueda

AU - Huang, Yi

AU - Jia, Wenlong

AU - Li, Zesong

AU - He, Minghui

AU - Sun, Liang

AU - Song, Pengfei

AU - Sun, Xiaojuan

AU - Zhao, Xiaokun

AU - Yang, Sangming

AU - Liang, Chaozhao

AU - Wan, Shengqing

AU - Zhou, Fangjian

AU - Chen, Chao

AU - Zhu, Jialou

AU - Li, Xianxin

AU - Jian, Minghan

AU - Zhou, Liang

AU - Ye, Rui

AU - Huang, Peide

AU - Chen, Jing

AU - Jiang, Tao

AU - Liu, Xiao

AU - Wang, Yong

AU - Zou, Jing

AU - Jiang, Zhimao

AU - Wu, Renhua

AU - Wu, Song

AU - Fan, Fan

AU - Zhang, Zhongfu

AU - Liu, Lin

AU - Yang, Ruilin

AU - Liu, Xingwang

AU - Wu, Haibo

AU - Yin, Weihua

AU - Zhao, Xia

AU - Liu, Yuchen

AU - Peng, Huanhuan

AU - Jiang, Binghua

AU - Feng, Qingxin

AU - Li, Cailing

AU - Xie, Jun

AU - Lu, Jingxiao

AU - Kristiansen, Karsten

AU - Li, Yingrui

AU - Zhang, Xiuqing

AU - Li, Songgang

AU - Wang, Jian

AU - Yang, Huanming

AU - Cai, Zhiming

AU - Wang, Jun

PY - 2012/1

Y1 - 2012/1

N2 - We sequenced whole exomes of ten clear cell renal cell carcinomas (ccRCCs) and performed a screen of ∼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 HIF1α and HIF2α 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.

AB - We sequenced whole exomes of ten clear cell renal cell carcinomas (ccRCCs) and performed a screen of ∼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 HIF1α and HIF2α 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.

KW - SOMATIC MUTATIONS

KW - CANCER

KW - Genetics & Heredity

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JO - Nature: New biology

JF - Nature: New biology

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ER -

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

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