1. Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma
- Author
-
Bing-Hua Jiang, Jing Chen, Tao Jiang, Yaoting Gui, Xiao Liu, Guangwu Guo, Aifa Tang, Yuchen Liu, Zhimao Jiang, Chaozhao Liang, Jun Xie, Xueda Hu, Xiuqing Zhang, Yingrui Li, Haibo Wu, Shengjie Gao, Zesong Li, Xingwang Liu, Huanhuan Peng, Zhiming Cai, Shengqing Wan, Xiaojuan Sun, Yong Wang, Liang Zhou, Fan Fan, Huanming Yang, Minghan Jian, Song Wu, Rui Ye, Lin Liu, Songgang Li, Xiaokun Zhao, Renhua Wu, Sangming Yang, Peide Huang, Jing Zou, Jian Wang, Cailing Li, Ruilin Yang, Zhongfu Zhang, Xianxin Li, Pengfei Song, Xia Zhao, Chao Chen, Jingxiao Lu, Jialou Zhu, Yi Huang, Liang Sun, Weihua Yin, Jun Wang, Qingxin Feng, Fangjian Zhou, Karsten Kristiansen, Wenlong Jia, and Minghui He
- Subjects
Proteolysis ,Cell ,medicine.disease_cause ,PBRM1 ,Mutation Rate ,Ubiquitin ,Basic Helix-Loop-Helix Transcription Factors ,Genetics ,medicine ,Humans ,Carcinoma, Renal Cell ,Gene ,biology ,medicine.diagnostic_test ,Ubiquitination ,Hypoxia-Inducible Factor 1, alpha Subunit ,medicine.disease ,Kidney Neoplasms ,Clear cell renal cell carcinoma ,medicine.anatomical_structure ,Mutation ,Cancer research ,biology.protein ,Carcinogenesis ,Clear cell ,Signal Transduction - 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.
- Published
- 2011