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

Huanming Yang, Zhiming Cai, Jun Wang and colleagues report whole-exome sequencing of 10 clear cell renal cell carcinomas followed by a screen of ~1,100 genes in a total of 98 tumors. They found 12 new disease-associated genes and detected frequent alterations in the ubiquitin-mediated proteolysis pa...

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Published inNature genetics Vol. 44; no. 1; pp. 17 - 19
Main Authors Guo, Guangwu, Gui, Yaoting, Gao, Shengjie, Tang, Aifa, Hu, Xueda, Huang, Yi, Jia, Wenlong, Li, Zesong, He, Minghui, Sun, Liang, Song, Pengfei, Sun, Xiaojuan, Zhao, Xiaokun, Yang, Sangming, Liang, Chaozhao, Wan, Shengqing, Zhou, Fangjian, Chen, Chao, Zhu, Jialou, Li, Xianxin, Jian, Minghan, Zhou, Liang, Ye, Rui, Huang, Peide, Chen, Jing, Jiang, Tao, Liu, Xiao, Wang, Yong, Zou, Jing, Jiang, Zhimao, Wu, Renhua, Wu, Song, Fan, Fan, Zhang, Zhongfu, Liu, Lin, Yang, Ruilin, Liu, Xingwang, Wu, Haibo, Yin, Weihua, Zhao, Xia, Liu, Yuchen, Peng, Huanhuan, Jiang, Binghua, Feng, Qingxin, Li, Cailing, Xie, Jun, Lu, Jingxiao, Kristiansen, Karsten, Li, Yingrui, Zhang, Xiuqing, Li, Songgang, Wang, Jian, Yang, Huanming, Cai, Zhiming, Wang, Jun
Format Journal Article
LanguageEnglish
Published New York Nature Publishing Group US 01.01.2012
Nature Publishing Group
Subjects
631/208/2489/144/68
692/699/67/589/1588/1351
Agriculture
Animal Genetics and Genomics
Basic Helix-Loop-Helix Transcription Factors - genetics
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
brief-communication
Cancer
Cancer Research
Carcinoma, Renal cell
Carcinoma, Renal Cell - genetics
Censuses
Epigenetics
Fundamental and applied biological sciences. Psychology
Gene Function
Gene mutations
Genetic aspects
Genetics of eukaryotes. Biological and molecular evolution
Health aspects
Human Genetics
Humans
Hypoxia
Hypoxia-Inducible Factor 1, alpha Subunit - genetics
Kidney Neoplasms - genetics
Kidneys
Medical sciences
Methods
Mutation
Mutation Rate
Nephrology. Urinary tract diseases
Pathogenesis
Physiological aspects
Proteolysis
Risk factors
Signal Transduction
Studies
Tumors of the urinary system
Ubiquitin
Ubiquitination
China
Kidney disease
Ubiquitin
Urinary system disease
Carcinoma
Gene
Proteolysis
Grawitz tumor
Malignant tumor
Mutation
Cancer
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Abstract Huanming Yang, Zhiming Cai, Jun Wang and colleagues report whole-exome sequencing of 10 clear cell renal cell carcinomas followed by a screen of ~1,100 genes in a total of 98 tumors. They found 12 new disease-associated genes and detected frequent alterations in the ubiquitin-mediated proteolysis pathway. 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.
AbstractList 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. [PUBLICATION ABSTRACT]
Huanming Yang, Zhiming Cai, Jun Wang and colleagues report whole-exome sequencing of 10 clear cell renal cell carcinomas followed by a screen of ~1,100 genes in a total of 98 tumors. They found 12 new disease-associated genes and detected frequent alterations in the ubiquitin-mediated proteolysis pathway. 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.
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 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.
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.
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.
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.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.
Audience Academic
Author Li, Songgang
Yang, Sangming
Wan, Shengqing
Liu, Xiao
Wang, Yong
Sun, Xiaojuan
Fan, Fan
Chen, Chao
Gao, Shengjie
Sun, Liang
Ye, Rui
Jiang, Tao
Wu, Song
Jia, Wenlong
Liu, Xingwang
Lu, Jingxiao
Tang, Aifa
Zhang, Zhongfu
Li, Cailing
Yang, Huanming
Zhang, Xiuqing
Li, Xianxin
Feng, Qingxin
He, Minghui
Zhou, Liang
Zhao, Xia
Zhu, Jialou
Yin, Weihua
Liu, Yuchen
Gui, Yaoting
Liang, Chaozhao
Hu, Xueda
Huang, Peide
Li, Zesong
Jian, Minghan
Yang, Ruilin
Peng, Huanhuan
Jiang, Binghua
Xie, Jun
Kristiansen, Karsten
Jiang, Zhimao
Cai, Zhiming
Wang, Jian
Guo, Guangwu
Zhou, Fangjian
Zou, Jing
Huang, Yi
Wu, Renhua
Wang, Jun
Liu, Lin
Li, Yingrui
Song, Pengfei
Zhao, Xiaokun
Wu, Haibo
Chen, Jing
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Keywords Kidney disease
Ubiquitin
Urinary system disease
Carcinoma
Gene
Proteolysis
Grawitz tumor
Malignant tumor
Mutation
Cancer
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Snippet Huanming Yang, Zhiming Cai, Jun Wang and colleagues report whole-exome sequencing of 10 clear cell renal cell carcinomas followed by a screen of ~1,100 genes...
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...
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...
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...
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SubjectTerms 631/208/2489/144/68
692/699/67/589/1588/1351
Agriculture
Animal Genetics and Genomics
Basic Helix-Loop-Helix Transcription Factors - genetics
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
brief-communication
Cancer
Cancer Research
Carcinoma, Renal cell
Carcinoma, Renal Cell - genetics
Censuses
Epigenetics
Fundamental and applied biological sciences. Psychology
Gene Function
Gene mutations
Genetic aspects
Genetics of eukaryotes. Biological and molecular evolution
Health aspects
Human Genetics
Humans
Hypoxia
Hypoxia-Inducible Factor 1, alpha Subunit - genetics
Kidney Neoplasms - genetics
Kidneys
Medical sciences
Methods
Mutation
Mutation Rate
Nephrology. Urinary tract diseases
Pathogenesis
Physiological aspects
Proteolysis
Risk factors
Signal Transduction
Studies
Tumors of the urinary system
Ubiquitin
Ubiquitination
Title Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma
URI https://link.springer.com/article/10.1038/ng.1014
https://www.ncbi.nlm.nih.gov/pubmed/22138691
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