Whole-genome and Transcriptome Sequencing of Prostate Cancer Identify New Genetic Alterations Driving Disease Progression
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Whole-genome and Transcriptome Sequencing of Prostate Cancer Identify New Genetic Alterations Driving Disease Progression. / Ren, Shancheng; Wei, Gong-Hong; Liu, Dongbing; Wang, Liguo; Hou, Yong; Zhu, Shida; Peng, Lihua; Zhang, Qin; Cheng, Yanbing; Su, Hong; Zhou, Xiuqing; Zhang, Jibin; Li, Fuqiang; Zheng, Hancheng; Zhao, Zhikun; Yin, Changjun; He, Zengquan; Gao, Xin; Zhau, Haiyen E.; Chu, Chia-Yi; Wu, Jason Boyang; Collins, Colin; Volik, Stanislav V; Bell, Robert; Huang, Jiaoti; Wu, Kui; Xu, Danfeng; Ye, Dingwei; Yu, Yongwei; Zhu, Lianhui; Qiao, Meng; Lee, Hang-Mao; Yang, Yuehong; Zhu, Yasheng; Shi, Xiaolei; Chen, Rui; Wang, Yang; Xu, Weidong; Cheng, Yanqiong; Xu, Chuanliang; Gao, Xu; Zhou, Tie; Yang, Bo; Hou, Jianguo; Liu, Li; Zhang, Zhensheng; Zhu, Yao; Qin, Chao; Shao, Pengfei; Pang, Jun; Chung, Leland W. K.; Xu, Jianfeng; Wu, Chin-Lee; Zhong, Weide; Xu, Xun; Li, Yingrui; Zhang, Xiuqing; Wang, Jian; Yang, Huanming; Wang, Jun; Huang, Haojie; Sun, Yinghao.
In: European Urology, Vol. 73, No. 3, 2018, p. 322-339.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Whole-genome and Transcriptome Sequencing of Prostate Cancer Identify New Genetic Alterations Driving Disease Progression
AU - Ren, Shancheng
AU - Wei, Gong-Hong
AU - Liu, Dongbing
AU - Wang, Liguo
AU - Hou, Yong
AU - Zhu, Shida
AU - Peng, Lihua
AU - Zhang, Qin
AU - Cheng, Yanbing
AU - Su, Hong
AU - Zhou, Xiuqing
AU - Zhang, Jibin
AU - Li, Fuqiang
AU - Zheng, Hancheng
AU - Zhao, Zhikun
AU - Yin, Changjun
AU - He, Zengquan
AU - Gao, Xin
AU - Zhau, Haiyen E.
AU - Chu, Chia-Yi
AU - Wu, Jason Boyang
AU - Collins, Colin
AU - Volik, Stanislav V
AU - Bell, Robert
AU - Huang, Jiaoti
AU - Wu, Kui
AU - Xu, Danfeng
AU - Ye, Dingwei
AU - Yu, Yongwei
AU - Zhu, Lianhui
AU - Qiao, Meng
AU - Lee, Hang-Mao
AU - Yang, Yuehong
AU - Zhu, Yasheng
AU - Shi, Xiaolei
AU - Chen, Rui
AU - Wang, Yang
AU - Xu, Weidong
AU - Cheng, Yanqiong
AU - Xu, Chuanliang
AU - Gao, Xu
AU - Zhou, Tie
AU - Yang, Bo
AU - Hou, Jianguo
AU - Liu, Li
AU - Zhang, Zhensheng
AU - Zhu, Yao
AU - Qin, Chao
AU - Shao, Pengfei
AU - Pang, Jun
AU - Chung, Leland W. K.
AU - Xu, Jianfeng
AU - Wu, Chin-Lee
AU - Zhong, Weide
AU - Xu, Xun
AU - Li, Yingrui
AU - Zhang, Xiuqing
AU - Wang, Jian
AU - Yang, Huanming
AU - Wang, Jun
AU - Huang, Haojie
AU - Sun, Yinghao
N1 - Copyright © 2017 European Association of Urology. All rights reserved.
PY - 2018
Y1 - 2018
N2 - BACKGROUND: Global disparities in prostate cancer (PCa) incidence highlight the urgent need to identify genomic abnormalities in prostate tumors in different ethnic populations including Asian men.OBJECTIVE: To systematically explore the genomic complexity and define disease-driven genetic alterations in PCa.DESIGN, SETTING, AND PARTICIPANTS: The study sequenced whole-genome and transcriptome of tumor-benign paired tissues from 65 treatment-naive Chinese PCa patients. Subsequent targeted deep sequencing of 293 PCa-relevant genes was performed in another cohort of 145 prostate tumors.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The genomic alteration landscape in PCa was analyzed using an integrated computational pipeline. Relationships with PCa progression and survival were analyzed using nonparametric test, log-rank, and multivariable Cox regression analyses.RESULTS AND LIMITATIONS: We demonstrated an association of high frequency of CHD1 deletion with a low rate of TMPRSS2-ERG fusion and relatively high percentage of mutations in androgen receptor upstream activator genes in Chinese patients. We identified five putative clustered deleted tumor suppressor genes and provided experimental and clinical evidence that PCDH9, deleted/loss in approximately 23% of tumors, functions as a novel tumor suppressor gene with prognostic potential in PCa. Furthermore, axon guidance pathway genes were frequently deregulated, including gain/amplification of PLXNA1 gene in approximately 17% of tumors. Functional and clinical data analyses showed that increased expression of PLXNA1 promoted prostate tumor growth and independently predicted prostate tumor biochemical recurrence, metastasis, and poor survival in multi-institutional cohorts of patients with PCa. A limitation of this study is that other genetic alterations were not experimentally investigated.CONCLUSIONS: There are shared and salient genetic characteristics of PCa in Chinese and Caucasian men. Novel genetic alterations in PCDH9 and PLXNA1 were associated with disease progression.PATIENT SUMMARY: We reported the first large-scale and comprehensive genomic data of prostate cancer from Asian population. Identification of these genetic alterations may help advance prostate cancer diagnosis, prognosis, and treatment.
AB - BACKGROUND: Global disparities in prostate cancer (PCa) incidence highlight the urgent need to identify genomic abnormalities in prostate tumors in different ethnic populations including Asian men.OBJECTIVE: To systematically explore the genomic complexity and define disease-driven genetic alterations in PCa.DESIGN, SETTING, AND PARTICIPANTS: The study sequenced whole-genome and transcriptome of tumor-benign paired tissues from 65 treatment-naive Chinese PCa patients. Subsequent targeted deep sequencing of 293 PCa-relevant genes was performed in another cohort of 145 prostate tumors.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The genomic alteration landscape in PCa was analyzed using an integrated computational pipeline. Relationships with PCa progression and survival were analyzed using nonparametric test, log-rank, and multivariable Cox regression analyses.RESULTS AND LIMITATIONS: We demonstrated an association of high frequency of CHD1 deletion with a low rate of TMPRSS2-ERG fusion and relatively high percentage of mutations in androgen receptor upstream activator genes in Chinese patients. We identified five putative clustered deleted tumor suppressor genes and provided experimental and clinical evidence that PCDH9, deleted/loss in approximately 23% of tumors, functions as a novel tumor suppressor gene with prognostic potential in PCa. Furthermore, axon guidance pathway genes were frequently deregulated, including gain/amplification of PLXNA1 gene in approximately 17% of tumors. Functional and clinical data analyses showed that increased expression of PLXNA1 promoted prostate tumor growth and independently predicted prostate tumor biochemical recurrence, metastasis, and poor survival in multi-institutional cohorts of patients with PCa. A limitation of this study is that other genetic alterations were not experimentally investigated.CONCLUSIONS: There are shared and salient genetic characteristics of PCa in Chinese and Caucasian men. Novel genetic alterations in PCDH9 and PLXNA1 were associated with disease progression.PATIENT SUMMARY: We reported the first large-scale and comprehensive genomic data of prostate cancer from Asian population. Identification of these genetic alterations may help advance prostate cancer diagnosis, prognosis, and treatment.
KW - Journal Article
U2 - 10.1016/j.eururo.2017.08.027
DO - 10.1016/j.eururo.2017.08.027
M3 - Journal article
C2 - 28927585
VL - 73
SP - 322
EP - 339
JO - European Urology
JF - European Urology
SN - 0302-2838
IS - 3
ER -
ID: 189866479