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.

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Acknowledgements

This work was supported by grants from the National High Technology Research and Development Program of China (863 Program, 2006AA02A302 to H.Y. 2009AA022707 to X.Z.), the Promotion Program for Shenzhen Key Laboratory, Shenzhen, China (CXB200903090055A and CXB201005250016A to Z.C.), and Research Fund for the Doctoral Program of Higher Education of China (20100001110100).

Author information

Author notes

    • Yaoting Gui
    • , Guangwu Guo
    • , Yi Huang
    • , Xueda Hu
    •  & Aifa Tang

    These authors contributed equally to this work.

Affiliations

  1. Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, China.

    • Yaoting Gui
    • , Yi Huang
    • , Aifa Tang
    • , Xianxin Li
    • , Liang Zhou
    • , Zesong Li
    • , Yong Wang
    • , Liang Sun
    • , Zhimao Jiang
    • , Jing Chen
    • , Song Wu
    • , Zhongfu Zhang
    • , Ruilin Yang
    • , Jun Zhao
    • , Congjie Xu
    • , Weihua Yin
    • , Zhichen Guan
    • , Jiongxian Ye
    • , Hong Zhang
    •  & Zhiming Cai
  2. BGI-Shenzhen, Shenzhen, China.

    • Guangwu Guo
    • , Xueda Hu
    • , Shengjie Gao
    • , Renhua Wu
    • , Chao Chen
    • , Minghui He
    • , Wenlong Jia
    • , Jinnong Chen
    • , Shangming Yang
    • , Shengqing Wan
    • , Rui Ye
    • , Zhisheng Liu
    • , Peide Huang
    • , Hui Jiang
    • , Hancheng Zheng
    • , Xingwang Liu
    • , Dafei Feng
    • , Jing Zou
    • , Jingxiang Li
    • , Karsten Kristiansen
    • , Yingrui Li
    • , Xiuqing Zhang
    • , Songgang Li
    • , Jian Wang
    • , Huanming Yang
    •  & Jun Wang
  3. Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China.

    • Aifa Tang
    • , Zesong Li
    • , Xiaojuan Sun
    •  & Zhiming Cai
  4. Department of Urology, Sun Yat-Sen University Cancer Center, Guangzhou, China.

    • Fangjian Zhou
  5. Department of Urology, the Second Xiangya Hospital of Central-Southern University, Changsha, China.

    • Xiaokun Zhao
  6. Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

    • Chaozhao Liang
  7. Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

    • Chunxiao Liu
  8. Department of Biology, University of Copenhagen, Copenhagen, Denmark.

    • Karsten Kristiansen
    •  & Jun Wang
  9. Cancer and Inflammation Program, National Cancer Institute, US National Institutes of Health (NIH), Frederick, Maryland, USA.

    • Michael L Nickerson
  10. Department of Surgery, University of Colorado Comprehensive Cancer Center, Aurora, Colorado, USA.

    • Dan Theodorescu
  11. Department of Pharmacology, University of Colorado Comprehensive Cancer Center, Aurora, Colorado, USA.

    • Dan Theodorescu

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Contributions

Jun Wang, Z.C., Jian Wang, H.Y., S.L. and Y.G. managed the project. A.T., X. Li, L.Z., Z. Li, F.Z., X. Zhao, C. Liang, C. Liu, Y.W., L.S., Z.J., Jing Chen, S. Wu, Z.Z., R. Yang, J. Zhao, C.X., Z.G., J.Y., H. Zhang and W.Y. prepared the samples. X.H., R.W., P.H., H.J., J.L. and X. Zhang performed the sequencing. Y.G., G.G., Y.H., S.G., C.C., M.H., W.J., R. Ye, Z. Liu, S. Wan, H. Zheng, K.K., M.L.N. and Y.L. performed the bioinformatic analysis. Y.H., X.H., Jinnong Chen, S.Y., X. Liu, D.F. and J. Zou performed the validation of somatic mutations. G.G. and Y.H. wrote the paper. Y.G., Jun Wang, Z.C., X.H., Y.L., D.T. and X.S. revised the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Huanming Yang or Jun Wang or Zhiming Cai.

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DOI

https://doi.org/10.1038/ng.907

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