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Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma |
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| 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 |
| Institution: | Shenzhen Key Laboratory of Transomics Biotechnologies, BGI-Shenzhen, Shenzhen, China. |
| 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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