Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation

Guangwu Guo; Xiaojuan Sun; Chao Chen; Song Wu; Peide Huang; Zesong Li; Michael Dean; Yi Huang; Wenlong Jia; Quan Zhou; Aifa Tang; Zuoquan Yang; Xianxin Li; Pengfei Song; Xiaokun Zhao; Rui Ye; Shiqiang Zhang; Zhao Lin; Mingfu Qi; Shengqing Wan; Liangfu Xie; Fan Fan; Michael L. Nickerson; Xiangjun Zou; Xueda Hu; Li Xing; Zhaojie Lv; Hongbin Mei; Shengjie Gao; Chaozhao Liang; Zhibo Gao; Jingxiao Lu; Yuan Yu; Chunxiao Liu; Lin Li; Xiaodong Fang; Zhimao Jiang; Jie Yang; Cailing Li; Xin Zhao; Jing Chen; Fang Zhang; Yongqi Lai; Zheguang Lin; Fangjian Zhou; Hao Chen; Hsiao Chang Chan; Shirley Tsang; Dan Theodorescu; Yingrui Li; Xiuqing Zhang; Jian Wang; Huanming Yang; Yaoting Gui; Jun Wang; Zhiming Cai

doi:10.1038/ng.2798

Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation

Guangwu Guo
, Xiaojuan Sun
, Chao Chen
, Song Wu
, Peide Huang
, Zesong Li
, Michael Dean
, Yi Huang
, Wenlong Jia
, Quan Zhou
, Aifa Tang
, Zuoquan Yang
, Xianxin Li
, Pengfei Song
, Xiaokun Zhao
, Rui Ye
, Shiqiang Zhang
, Zhao Lin
, Mingfu Qi
, Shengqing Wan

Liangfu Xie, Fan Fan, Michael L. Nickerson, Xiangjun Zou, Xueda Hu, Li Xing, Zhaojie Lv, Hongbin Mei, Shengjie Gao, Chaozhao Liang, Zhibo Gao, Jingxiao Lu, Yuan Yu, Chunxiao Liu, Lin Li, Xiaodong Fang, Zhimao Jiang, Jie Yang, Cailing Li, Xin Zhao, Jing Chen, Fang Zhang, Yongqi Lai, Zheguang Lin, Fangjian Zhou, Hao Chen, Hsiao Chang Chan, Shirley Tsang, Dan Theodorescu, Yingrui Li, Xiuqing Zhang, Jian Wang, Huanming Yang, Yaoting Gui, Jun Wang, Zhiming Cai

Shenzhen University
BGI-Shenzhen
Sun Yat-Sen University
Sun Yat-Sen University Cancer Center
National Institutes of Health
Peking University
Central South University
Anhui Medical University
Southern Medical University
Chinese University of Hong Kong
BioMatrix, LLC
University of Colorado Anschutz Medical Campus
University of Copenhagen

Research output: Contribution to journal › Article › peer-review

408 Scopus citations

Abstract

Bladder cancer is one of the most common cancers worldwide, with transitional cell carcinoma (TCC) being the predominant form. Here we report a genomic analysis of TCC by both whole-genome and whole-exome sequencing of 99 individuals with TCC. Beyond confirming recurrent mutations in genes previously identified as being mutated in TCC, we identified additional altered genes and pathways that were implicated in TCC. Notably, we discovered frequent alterations in STAG2 and ESPL1, two genes involved in the sister chromatid cohesion and segregation (SCCS) process. Furthermore, we also detected a recurrent fusion involving FGFR3 and TACC3, another component of SCCS, by transcriptome sequencing of 42 DNA-sequenced tumors. Overall, 32 of the 99 tumors (32%) harbored genetic alterations in the SCCS process. Our analysis provides evidence that genetic alterations affecting the SCCS process may be involved in bladder tumorigenesis and identifies a new therapeutic possibility for bladder cancer.

Original language	English
Pages (from-to)	1459-1463
Number of pages	5
Journal	Nature Genetics
Volume	45
Issue number	12
DOIs	https://doi.org/10.1038/ng.2798
State	Published - Dec 2013
Externally published	Yes

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1038/ng.2798

Cite this

Guo, G., Sun, X., Chen, C., Wu, S., Huang, P., Li, Z., Dean, M., Huang, Y., Jia, W., Zhou, Q., Tang, A., Yang, Z., Li, X., Song, P., Zhao, X., Ye, R., Zhang, S., Lin, Z., Qi, M., ... Cai, Z. (2013). Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation. Nature Genetics, 45(12), 1459-1463. https://doi.org/10.1038/ng.2798

@article{8ee6e8cdfc4247a38515204690287cb0,

title = "Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation",

abstract = "Bladder cancer is one of the most common cancers worldwide, with transitional cell carcinoma (TCC) being the predominant form. Here we report a genomic analysis of TCC by both whole-genome and whole-exome sequencing of 99 individuals with TCC. Beyond confirming recurrent mutations in genes previously identified as being mutated in TCC, we identified additional altered genes and pathways that were implicated in TCC. Notably, we discovered frequent alterations in STAG2 and ESPL1, two genes involved in the sister chromatid cohesion and segregation (SCCS) process. Furthermore, we also detected a recurrent fusion involving FGFR3 and TACC3, another component of SCCS, by transcriptome sequencing of 42 DNA-sequenced tumors. Overall, 32 of the 99 tumors (32\%) harbored genetic alterations in the SCCS process. Our analysis provides evidence that genetic alterations affecting the SCCS process may be involved in bladder tumorigenesis and identifies a new therapeutic possibility for bladder cancer.",

author = "Guangwu Guo and Xiaojuan Sun and Chao Chen and Song Wu and Peide Huang and Zesong Li and Michael Dean and Yi Huang and Wenlong Jia and Quan Zhou and Aifa Tang and Zuoquan Yang and Xianxin Li and Pengfei Song and Xiaokun Zhao and Rui Ye and Shiqiang Zhang and Zhao Lin and Mingfu Qi and Shengqing Wan and Liangfu Xie and Fan Fan and Nickerson, \{Michael L.\} and Xiangjun Zou and Xueda Hu and Li Xing and Zhaojie Lv and Hongbin Mei and Shengjie Gao and Chaozhao Liang and Zhibo Gao and Jingxiao Lu and Yuan Yu and Chunxiao Liu and Lin Li and Xiaodong Fang and Zhimao Jiang and Jie Yang and Cailing Li and Xin Zhao and Jing Chen and Fang Zhang and Yongqi Lai and Zheguang Lin and Fangjian Zhou and Hao Chen and Chan, \{Hsiao Chang\} and Shirley Tsang and Dan Theodorescu and Yingrui Li and Xiuqing Zhang and Jian Wang and Huanming Yang and Yaoting Gui and Jun Wang and Zhiming Cai",

year = "2013",

month = dec,

doi = "10.1038/ng.2798",

language = "英语",

volume = "45",

pages = "1459--1463",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "12",

}

Guo, G, Sun, X, Chen, C, Wu, S, Huang, P, Li, Z, Dean, M, Huang, Y, Jia, W, Zhou, Q, Tang, A, Yang, Z, Li, X, Song, P, Zhao, X, Ye, R, Zhang, S, Lin, Z, Qi, M, Wan, S, Xie, L, Fan, F, Nickerson, ML, Zou, X, Hu, X, Xing, L, Lv, Z, Mei, H, Gao, S, Liang, C, Gao, Z, Lu, J, Yu, Y, Liu, C, Li, L, Fang, X, Jiang, Z, Yang, J, Li, C, Zhao, X, Chen, J, Zhang, F, Lai, Y, Lin, Z, Zhou, F, Chen, H, Chan, HC, Tsang, S, Theodorescu, D, Li, Y, Zhang, X, Wang, J, Yang, H, Gui, Y, Wang, J & Cai, Z 2013, 'Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation', Nature Genetics, vol. 45, no. 12, pp. 1459-1463. https://doi.org/10.1038/ng.2798

TY - JOUR

T1 - Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation

AU - Guo, Guangwu

AU - Sun, Xiaojuan

AU - Chen, Chao

AU - Wu, Song

AU - Huang, Peide

AU - Li, Zesong

AU - Dean, Michael

AU - Huang, Yi

AU - Jia, Wenlong

AU - Zhou, Quan

AU - Tang, Aifa

AU - Yang, Zuoquan

AU - Li, Xianxin

AU - Song, Pengfei

AU - Zhao, Xiaokun

AU - Ye, Rui

AU - Zhang, Shiqiang

AU - Lin, Zhao

AU - Qi, Mingfu

AU - Wan, Shengqing

AU - Xie, Liangfu

AU - Fan, Fan

AU - Nickerson, Michael L.

AU - Zou, Xiangjun

AU - Hu, Xueda

AU - Xing, Li

AU - Lv, Zhaojie

AU - Mei, Hongbin

AU - Gao, Shengjie

AU - Liang, Chaozhao

AU - Gao, Zhibo

AU - Lu, Jingxiao

AU - Yu, Yuan

AU - Liu, Chunxiao

AU - Li, Lin

AU - Fang, Xiaodong

AU - Jiang, Zhimao

AU - Yang, Jie

AU - Li, Cailing

AU - Zhao, Xin

AU - Chen, Jing

AU - Zhang, Fang

AU - Lai, Yongqi

AU - Lin, Zheguang

AU - Zhou, Fangjian

AU - Chen, Hao

AU - Chan, Hsiao Chang

AU - Tsang, Shirley

AU - Theodorescu, Dan

AU - Li, Yingrui

AU - Zhang, Xiuqing

AU - Wang, Jian

AU - Yang, Huanming

AU - Gui, Yaoting

AU - Wang, Jun

AU - Cai, Zhiming

PY - 2013/12

Y1 - 2013/12

N2 - Bladder cancer is one of the most common cancers worldwide, with transitional cell carcinoma (TCC) being the predominant form. Here we report a genomic analysis of TCC by both whole-genome and whole-exome sequencing of 99 individuals with TCC. Beyond confirming recurrent mutations in genes previously identified as being mutated in TCC, we identified additional altered genes and pathways that were implicated in TCC. Notably, we discovered frequent alterations in STAG2 and ESPL1, two genes involved in the sister chromatid cohesion and segregation (SCCS) process. Furthermore, we also detected a recurrent fusion involving FGFR3 and TACC3, another component of SCCS, by transcriptome sequencing of 42 DNA-sequenced tumors. Overall, 32 of the 99 tumors (32%) harbored genetic alterations in the SCCS process. Our analysis provides evidence that genetic alterations affecting the SCCS process may be involved in bladder tumorigenesis and identifies a new therapeutic possibility for bladder cancer.

AB - Bladder cancer is one of the most common cancers worldwide, with transitional cell carcinoma (TCC) being the predominant form. Here we report a genomic analysis of TCC by both whole-genome and whole-exome sequencing of 99 individuals with TCC. Beyond confirming recurrent mutations in genes previously identified as being mutated in TCC, we identified additional altered genes and pathways that were implicated in TCC. Notably, we discovered frequent alterations in STAG2 and ESPL1, two genes involved in the sister chromatid cohesion and segregation (SCCS) process. Furthermore, we also detected a recurrent fusion involving FGFR3 and TACC3, another component of SCCS, by transcriptome sequencing of 42 DNA-sequenced tumors. Overall, 32 of the 99 tumors (32%) harbored genetic alterations in the SCCS process. Our analysis provides evidence that genetic alterations affecting the SCCS process may be involved in bladder tumorigenesis and identifies a new therapeutic possibility for bladder cancer.

UR - https://www.scopus.com/pages/publications/84888380730

U2 - 10.1038/ng.2798

DO - 10.1038/ng.2798

M3 - 文章

C2 - 24121792

AN - SCOPUS:84888380730

SN - 1061-4036

VL - 45

SP - 1459

EP - 1463

JO - Nature Genetics

JF - Nature Genetics

IS - 12

ER -

Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation

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