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.
authors.affiliation: Shenzhen Key Laboratory of Transomics Biotechnologies, BGI-Shenzhen, Shenzhen, China.
authors.forename: Guangwu
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authors.lastname: Guo
authors.forename: Yaoting
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authors.lastname: Gui
authors.forename: Shengjie
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authors.lastname: Gao
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authors.lastname: Tang
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authors.lastname: Hu
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authors.lastname: Huang
authors.forename: Wenlong
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authors.forename: Minghui
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authors.lastname: He
authors.forename: Liang
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authors.lastname: Sun
authors.forename: Pengfei
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authors.lastname: Song
authors.forename: Xiaojuan
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authors.lastname: Sun
authors.forename: Xiaokun
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authors.lastname: Zhao
authors.forename: Sangming
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authors.lastname: Yang
authors.forename: Chaozhao
authors.initials: C
authors.lastname: Liang
authors.forename: Shengqing
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authors.lastname: Wan
authors.forename: Fangjian
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authors.lastname: Zhou
authors.forename: Chao
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authors.lastname: Chen
authors.forename: Jialou
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authors.lastname: Zhu
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authors.lastname: Li
authors.forename: Minghan
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authors.lastname: Jian
authors.forename: Liang
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authors.lastname: Zhou
authors.forename: Rui
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authors.lastname: Ye
authors.forename: Peide
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authors.lastname: Huang
authors.forename: Jing
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authors.lastname: Chen
authors.forename: Tao
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authors.lastname: Jiang
authors.forename: Xiao
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authors.lastname: Liu
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authors.lastname: Wang
authors.forename: Jing
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authors.lastname: Zou
authors.forename: Zhimao
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authors.lastname: Jiang
authors.forename: Renhua
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authors.lastname: Wu
authors.forename: Song
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authors.lastname: Wu
authors.forename: Fan
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authors.lastname: Fan
authors.forename: Zhongfu
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authors.lastname: Zhang
authors.forename: Lin
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authors.lastname: Liu
authors.forename: Ruilin
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authors.lastname: Yang
authors.forename: Xingwang
authors.initials: X
authors.lastname: Liu
authors.forename: Haibo
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authors.lastname: Wu
authors.forename: Weihua
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authors.lastname: Yin
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Liu
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Peng
authors.forename: Binghua
authors.initials: B
authors.lastname: Jiang
authors.forename: Qingxin
authors.initials: Q
authors.lastname: Feng
authors.forename: Cailing
authors.initials: C
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Xie
authors.forename: Jingxiao
authors.initials: J
authors.lastname: Lu
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.forename: Yingrui
authors.initials: Y
authors.lastname: Li
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Zhang
authors.forename: Songgang
authors.initials: S
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Huanming
authors.initials: H
authors.lastname: Yang
authors.forename: Zhiming
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authors.lastname: Cai
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D007680:Kidney Neoplasms / Q000235:genetics*; D009154:Mutation; D059645:Mutation Rate; D059748:Proteolysis; D015398:Signal Transduction; D054875:Ubiquitination; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000099162:Endothelial PAS Domain-Containing Protein 1