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

• Published in: Nature 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
• Language: English
• 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
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.1014

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.