Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder

Yaoting Gui, Guangwu Guo, Yi Huang, Xueda Hu, Aifa Tang, Shengjie Gao, Renhua Wu, Chao Chen, Xianxin Li, Liang Zhou, Minghui He, Zesong Li, Xiaojuan Sun, Wenlong Jia, Jinnong Chen, Shangming Yang, Fangjian Zhou, Xiaokun Zhao, Shengqing Wan, Rui YeChaozhao Liang, chunxiao Liu, Peide Huang, Chunxiao Liu, Hui Jiang, Yong Wang, Hancheng Zheng, Liang Sun, Xingwang Liu, Zhimao Jiang, Dafei Feng, Xi Jing Chen, Song Wu, Jing Zou, Zhongfu Zhang, Ruilin Yang, Jun Zhao, Congjie Xu, Weihua Yin, Zhichen Guan, Jiongxian Ye, Hong Zhang, Jingxiang Li, Karsten Kristiansen, Michael L Nickerson, Dan Theodorescu, Yingrui Li, Xiuqing Zhang, Songgang Li, Jian Wang, Huanming Yang, Jun Wang, Zhiming Cai

520 Citations (Scopus)

Abstract

Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.
Original languageEnglish
JournalNature Genetics
Volume43
Issue number9
Pages (from-to)875-8
Number of pages4
ISSN1061-4036
DOIs
Publication statusPublished - Sept 2011

Keywords

  • Carcinoma, Transitional Cell
  • Chromatin Assembly and Disassembly
  • Chromosome Aberrations
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mutation
  • Urinary Bladder Neoplasms

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