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.
authors.affiliation: 1] Department of Urological Surgery, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China. [2] BGI-Shenzhen, Shenzhen, China. [3].
authors.forename: Guangwu
authors.initials: G
authors.lastname: Guo
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Sun
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.forename: Song
authors.initials: S
authors.lastname: Wu
authors.forename: Peide
authors.initials: P
authors.lastname: Huang
authors.forename: Zesong
authors.initials: Z
authors.lastname: Li
authors.forename: Michael
authors.initials: M
authors.lastname: Dean
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.forename: Wenlong
authors.initials: W
authors.lastname: Jia
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhou
authors.forename: Aifa
authors.initials: A
authors.lastname: Tang
authors.forename: Zuoquan
authors.initials: Z
authors.lastname: Yang
authors.forename: Xianxin
authors.initials: X
authors.lastname: Li
authors.forename: Pengfei
authors.initials: P
authors.lastname: Song
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Zhao
authors.forename: Rui
authors.initials: R
authors.lastname: Ye
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Zhang
authors.forename: Zhao
authors.initials: Z
authors.lastname: Lin
authors.forename: Mingfu
authors.initials: M
authors.lastname: Qi
authors.forename: Shengqing
authors.initials: S
authors.lastname: Wan
authors.forename: Liangfu
authors.initials: L
authors.lastname: Xie
authors.forename: Fan
authors.initials: F
authors.lastname: Fan
authors.forename: Michael L
authors.initials: ML
authors.lastname: Nickerson
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Zou
authors.forename: Xueda
authors.initials: X
authors.lastname: Hu
authors.forename: Li
authors.initials: L
authors.lastname: Xing
authors.forename: Zhaojie
authors.initials: Z
authors.lastname: Lv
authors.forename: Hongbin
authors.initials: H
authors.lastname: Mei
authors.forename: Shengjie
authors.initials: S
authors.lastname: Gao
authors.forename: Chaozhao
authors.initials: C
authors.lastname: Liang
authors.forename: Zhibo
authors.initials: Z
authors.lastname: Gao
authors.forename: Jingxiao
authors.initials: J
authors.lastname: Lu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yu
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Fang
authors.forename: Zhimao
authors.initials: Z
authors.lastname: Jiang
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Cailing
authors.initials: C
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.forename: Yongqi
authors.initials: Y
authors.lastname: Lai
authors.forename: Zheguang
authors.initials: Z
authors.lastname: Lin
authors.forename: Fangjian
authors.initials: F
authors.lastname: Zhou
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Hsiao Chang
authors.initials: HC
authors.lastname: Chan
authors.forename: Shirley
authors.initials: S
authors.lastname: Tsang
authors.forename: Dan
authors.initials: D
authors.lastname: Theodorescu
authors.forename: Yingrui
authors.initials: Y
authors.lastname: Li
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Huanming
authors.initials: H
authors.lastname: Yang
authors.forename: Yaoting
authors.initials: Y
authors.lastname: Gui
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Cai
mesh_terms: D001483:Base Sequence; D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D020090:Chromosome Segregation / Q000235:genetics*; D059472:Exome / Q000235:genetics*; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D012854:Sister Chromatid Exchange / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics*