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

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.

SUBMITTER: Gui Y 

PROVIDER: S-EPMC5373841 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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

Gui Yaoting Y   Guo Guangwu G   Huang Yi Y   Hu Xueda X   Tang Aifa A   Gao Shengjie S   Wu Renhua R   Chen Chao C   Li Xianxin X   Zhou Liang L   He Minghui M   Li Zesong Z   Sun Xiaojuan X   Jia Wenlong W   Chen Jinnong J   Yang Shangming S   Zhou Fangjian F   Zhao Xiaokun X   Wan Shengqing S   Ye Rui R   Liang Chaozhao C   Liu Zhisheng Z   Huang Peide P   Liu Chunxiao C   Jiang Hui H   Wang Yong Y   Zheng Hancheng H   Sun Liang L   Liu Xingwang X   Jiang Zhimao Z   Feng Dafei D   Chen Jing J   Wu Song S   Zou Jing J   Zhang Zhongfu Z   Yang Ruilin R   Zhao Jun J   Xu Congjie C   Yin Weihua W   Guan Zhichen Z   Ye Jiongxian J   Zhang Hong H   Li Jingxiang J   Kristiansen Karsten K   Nickerson Michael L ML   Theodorescu Dan D   Li Yingrui Y   Zhang Xiuqing X   Li Songgang S   Wang Jian J   Yang Huanming H   Wang Jun J   Cai Zhiming Z  

Nature genetics 20110807 9

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) i  ...[more]

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