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

被引：590

作者：

Gui, Yaoting ^{[1
]}

Guo, Guangwu ^{[2
]}

Huang, Yi ^{[1
]}

Hu, Xueda ^{[2
]}

Tang, Aifa ^{[1
,3
]}

Gao, Shengjie ^{[2
]}

Wu, Renhua ^{[2
]}

Chen, Chao ^{[2
]}

Li, Xianxin ^{[1
]}

Zhou, Liang ^{[1
]}

He, Minghui ^{[2
]}

Li, Zesong ^{[1
,3
]}

Sun, Xiaojuan ^{[3
]}

Jia, Wenlong ^{[2
]}

Chen, Jinnong ^{[2
]}

Yang, Shangming ^{[2
]}

Zhou, Fangjian ^{[4
]}

Zhao, Xiaokun ^{[5
]}

Wan, Shengqing ^{[2
]}

Ye, Rui ^{[2
]}

Liang, Chaozhao ^{[6
]}

Liu, Zhisheng ^{[2
]}

Huang, Peide ^{[2
]}

Liu, Chunxiao ^{[7
]}

Jiang, Hui ^{[2
]}

Wang, Yong ^{[1
]}

Zheng, Hancheng ^{[2
]}

Sun, Liang ^{[1
]}

Liu, Xingwang ^{[2
]}

Jiang, Zhimao ^{[1
]}

Feng, Dafei ^{[2
]}

Chen, Jing ^{[1
]}

Wu, Song ^{[1
]}

Zou, Jing ^{[2
]}

Zhang, Zhongfu ^{[1
]}

Yang, Ruilin ^{[1
]}

Zhao, Jun ^{[1
]}

Xu, Congjie ^{[1
]}

Yin, Weihua ^{[1
]}

Guan, Zhichen ^{[1
]}

Ye, Jiongxian ^{[1
]}

Zhang, Hong ^{[1
]}

Li, Jingxiang ^{[2
]}

Kristiansen, Karsten ^{[2
,8
]}

Nickerson, Michael L. ^{[9
]}

Theodorescu, Dan ^{[10
,11
]}

Li, Yingrui ^{[2
]}

Zhang, Xiuqing ^{[2
]}

Li, Songgang ^{[2
]}

Wang, Jian ^{[2
]}

机构：

[1] Peking Univ, Shenzhen Hosp, Guangdong & Shenzhen Key Lab Male Reprod Med & Ge, Inst Urol,Shenzhen PKU HKUST Med Ctr, Shenzhen, Peoples R China

[2] BGI Shenzhen, Shenzhen, Peoples R China

[3] Shenzhen Univ, Affiliated Hosp 1, Shenzhen Peoples Hosp 2, Shenzhen, Peoples R China

[4] Sun Yat Sen Univ, Ctr Canc, Dept Urol, Guangzhou 510275, Guangdong, Peoples R China

[5] Cent So Univ, Dept Urol, Xiangya Hosp 2, Changsha, Hunan, Peoples R China

[6] Anhui Med Univ, Affiliated Hosp 1, Dept Urol, Hefei, Peoples R China

[7] So Med Univ, Zhujiang Hosp, Dept Urol, Guangzhou, Guangdong, Peoples R China

[8] Univ Copenhagen, Dept Biol, Copenhagen, Denmark

[9] NCI, Canc & Inflammat Program, US Natl Inst Hlth NIH, Frederick, MD 21701 USA

[10] Univ Colorado, Dept Surg, Ctr Comprehens Canc, Aurora, CO USA

[11] Univ Colorado, Dept Pharmacol, Ctr Comprehens Canc, Aurora, CO USA

来源：

NATURE GENETICS | 2011年 / 43卷 / 09期

基金：

高等学校博士学科点专项科研基金; 国家高技术研究发展计划(863计划);

关键词：

SOMATIC MUTATIONS; CANCER; PATHWAYS; FGFR3;

D O I：

10.1038/ng.907

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：875 / 878

页数：4

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