Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway

Maolan Li; Zhou Zhang; Xiaoguang Li; Junyi Ye; Xiangsong Wu; Zhujun Tan; Chang Liu; Baiyong Shen; Xu An Wang; Wenguang Wu; Daizhan Zhou; Di Zhang; Ting Wang; Bingya Liu; Kai Qu; Qichen Ding; Hao Weng; Qian Ding; Jiasheng Mu; Yijun Shu; Runfa Bao; Yang Cao; Peizhan Chen; Tianyu Liu; Lin Jiang; Yunping Hu; Ping Dong; Jun Gu; Wei Lu; Weibin Shi; Jianhua Lu; Wei Gong; Zhaohui Tang; Yong Zhang; Xuefeng Wang; Y. Eugene Chin; Xiaoling Weng; Hong Zhang; Wei Tang; Yonglan Zheng; Lin He; Hui Wang; Yun Liiu; Yingbin Liu

doi:10.1038/ng.3030

Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway

Maolan Li
, Zhou Zhang
, Xiaoguang Li
, Junyi Ye
, Xiangsong Wu
, Zhujun Tan
, Chang Liu
, Baiyong Shen
, Xu An Wang
, Wenguang Wu
, Daizhan Zhou
, Di Zhang
, Ting Wang
, Bingya Liu
, Kai Qu
, Qichen Ding
, Hao Weng
, Qian Ding
, Jiasheng Mu
, Yijun Shu

Runfa Bao, Yang Cao, Peizhan Chen, Tianyu Liu, Lin Jiang, Yunping Hu, Ping Dong, Jun Gu, Wei Lu, Weibin Shi, Jianhua Lu, Wei Gong, Zhaohui Tang, Yong Zhang, Xuefeng Wang, Y. Eugene Chin, Xiaoling Weng, Hong Zhang, Wei Tang, Yonglan Zheng, Lin He, Hui Wang, Yun Liiu, Yingbin Liu

医学部

Shanghai Jiao Tong University
University of Chinese Academy of Sciences
Fudan University
CAS - Shanghai Institute of Nutrition and Health
National Institutes of Health
The University of Chicago
Zhejiang University
Ministry of Health of People's Republic of China

科研成果: 期刊稿件 › 文章 › 同行评审

411 引用（Scopus）

摘要

Individuals with gallbladder carcinoma (GBC), the most aggressive malignancy of the biliary tract, have a poor prognosis. Here we report the identification of somatic mutations for GBC in 57 tumor-normal pairs through a combination of exome sequencing and ultra-deep sequencing of cancer-related genes. The mutation pattern is defined by a dominant prevalence of C>T mutations at TCN sites. Genes with a significant frequency (false discovery rate (FDR) < 0.05) of non-silent mutations include TP53 (47.1%), KRAS (7.8%) and ERBB3 (11.8%). Moreover, ErbB signaling (including EGFR, ERBB2, ERBB3, ERBB4 and their downstream genes) is the most extensively mutated pathway, affecting 36.8% (21/57) of the GBC samples. Multivariate analyses further show that cases with ErbB pathway mutations have a worse outcome (P = 0.001). These findings provide insight into the somatic mutational landscape in GBC and highlight the key role of the ErbB signaling pathway in GBC pathogenesis.

源语言	英语
页（从-至）	872-876
页数	5
期刊	Nature Genetics
卷	46
期	8
DOI	https://doi.org/10.1038/ng.3030
出版状态	已出版 - 8月 2014

联合国可持续发展目标

此成果有助于实现下列可持续发展目标：

可持续发展目标 3 良好健康与福祉

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10.1038/ng.3030

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Li, M., Zhang, Z., Li, X., Ye, J., Wu, X., Tan, Z., Liu, C., Shen, B., Wang, X. A., Wu, W., Zhou, D., Zhang, D., Wang, T., Liu, B., Qu, K., Ding, Q., Weng, H., Ding, Q., Mu, J., ... Liu, Y. (2014). Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway. Nature Genetics, 46(8), 872-876. https://doi.org/10.1038/ng.3030

@article{4d916739181045159c1e7353c43b2c3b,

title = "Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway",

abstract = "Individuals with gallbladder carcinoma (GBC), the most aggressive malignancy of the biliary tract, have a poor prognosis. Here we report the identification of somatic mutations for GBC in 57 tumor-normal pairs through a combination of exome sequencing and ultra-deep sequencing of cancer-related genes. The mutation pattern is defined by a dominant prevalence of C>T mutations at TCN sites. Genes with a significant frequency (false discovery rate (FDR) < 0.05) of non-silent mutations include TP53 (47.1\%), KRAS (7.8\%) and ERBB3 (11.8\%). Moreover, ErbB signaling (including EGFR, ERBB2, ERBB3, ERBB4 and their downstream genes) is the most extensively mutated pathway, affecting 36.8\% (21/57) of the GBC samples. Multivariate analyses further show that cases with ErbB pathway mutations have a worse outcome (P = 0.001). These findings provide insight into the somatic mutational landscape in GBC and highlight the key role of the ErbB signaling pathway in GBC pathogenesis.",

author = "Maolan Li and Zhou Zhang and Xiaoguang Li and Junyi Ye and Xiangsong Wu and Zhujun Tan and Chang Liu and Baiyong Shen and Wang, \{Xu An\} and Wenguang Wu and Daizhan Zhou and Di Zhang and Ting Wang and Bingya Liu and Kai Qu and Qichen Ding and Hao Weng and Qian Ding and Jiasheng Mu and Yijun Shu and Runfa Bao and Yang Cao and Peizhan Chen and Tianyu Liu and Lin Jiang and Yunping Hu and Ping Dong and Jun Gu and Wei Lu and Weibin Shi and Jianhua Lu and Wei Gong and Zhaohui Tang and Yong Zhang and Xuefeng Wang and Chin, \{Y. Eugene\} and Xiaoling Weng and Hong Zhang and Wei Tang and Yonglan Zheng and Lin He and Hui Wang and Yun Liiu and Yingbin Liu",

year = "2014",

month = aug,

doi = "10.1038/ng.3030",

language = "英语",

volume = "46",

pages = "872--876",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "8",

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Li, M, Zhang, Z, Li, X, Ye, J, Wu, X, Tan, Z, Liu, C, Shen, B, Wang, XA, Wu, W, Zhou, D, Zhang, D, Wang, T, Liu, B, Qu, K, Ding, Q, Weng, H, Ding, Q, Mu, J, Shu, Y, Bao, R, Cao, Y, Chen, P, Liu, T, Jiang, L, Hu, Y, Dong, P, Gu, J, Lu, W, Shi, W, Lu, J, Gong, W, Tang, Z, Zhang, Y, Wang, X, Chin, YE, Weng, X, Zhang, H, Tang, W, Zheng, Y, He, L, Wang, H, Liiu, Y & Liu, Y 2014, 'Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway', Nature Genetics, 卷 46, 号码 8, 页码 872-876. https://doi.org/10.1038/ng.3030

TY - JOUR

T1 - Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway

AU - Li, Maolan

AU - Zhang, Zhou

AU - Li, Xiaoguang

AU - Ye, Junyi

AU - Wu, Xiangsong

AU - Tan, Zhujun

AU - Liu, Chang

AU - Shen, Baiyong

AU - Wang, Xu An

AU - Wu, Wenguang

AU - Zhou, Daizhan

AU - Zhang, Di

AU - Wang, Ting

AU - Liu, Bingya

AU - Qu, Kai

AU - Ding, Qichen

AU - Weng, Hao

AU - Ding, Qian

AU - Mu, Jiasheng

AU - Shu, Yijun

AU - Bao, Runfa

AU - Cao, Yang

AU - Chen, Peizhan

AU - Liu, Tianyu

AU - Jiang, Lin

AU - Hu, Yunping

AU - Dong, Ping

AU - Gu, Jun

AU - Lu, Wei

AU - Shi, Weibin

AU - Lu, Jianhua

AU - Gong, Wei

AU - Tang, Zhaohui

AU - Zhang, Yong

AU - Wang, Xuefeng

AU - Chin, Y. Eugene

AU - Weng, Xiaoling

AU - Zhang, Hong

AU - Tang, Wei

AU - Zheng, Yonglan

AU - He, Lin

AU - Wang, Hui

AU - Liiu, Yun

AU - Liu, Yingbin

PY - 2014/8

Y1 - 2014/8

N2 - Individuals with gallbladder carcinoma (GBC), the most aggressive malignancy of the biliary tract, have a poor prognosis. Here we report the identification of somatic mutations for GBC in 57 tumor-normal pairs through a combination of exome sequencing and ultra-deep sequencing of cancer-related genes. The mutation pattern is defined by a dominant prevalence of C>T mutations at TCN sites. Genes with a significant frequency (false discovery rate (FDR) < 0.05) of non-silent mutations include TP53 (47.1%), KRAS (7.8%) and ERBB3 (11.8%). Moreover, ErbB signaling (including EGFR, ERBB2, ERBB3, ERBB4 and their downstream genes) is the most extensively mutated pathway, affecting 36.8% (21/57) of the GBC samples. Multivariate analyses further show that cases with ErbB pathway mutations have a worse outcome (P = 0.001). These findings provide insight into the somatic mutational landscape in GBC and highlight the key role of the ErbB signaling pathway in GBC pathogenesis.

AB - Individuals with gallbladder carcinoma (GBC), the most aggressive malignancy of the biliary tract, have a poor prognosis. Here we report the identification of somatic mutations for GBC in 57 tumor-normal pairs through a combination of exome sequencing and ultra-deep sequencing of cancer-related genes. The mutation pattern is defined by a dominant prevalence of C>T mutations at TCN sites. Genes with a significant frequency (false discovery rate (FDR) < 0.05) of non-silent mutations include TP53 (47.1%), KRAS (7.8%) and ERBB3 (11.8%). Moreover, ErbB signaling (including EGFR, ERBB2, ERBB3, ERBB4 and their downstream genes) is the most extensively mutated pathway, affecting 36.8% (21/57) of the GBC samples. Multivariate analyses further show that cases with ErbB pathway mutations have a worse outcome (P = 0.001). These findings provide insight into the somatic mutational landscape in GBC and highlight the key role of the ErbB signaling pathway in GBC pathogenesis.

UR - https://www.scopus.com/pages/publications/84905721813

U2 - 10.1038/ng.3030

DO - 10.1038/ng.3030

M3 - 文章

C2 - 24997986

AN - SCOPUS:84905721813

SN - 1061-4036

VL - 46

SP - 872

EP - 876

JO - Nature Genetics

JF - Nature Genetics

IS - 8

ER -

Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway

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