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).
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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.
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Gui, Y., Guo, G., Huang, Y. et al. Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder. Nat Genet 43, 875–878 (2011). https://doi.org/10.1038/ng.907
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DOI: https://doi.org/10.1038/ng.907
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