Whole-genome sequencing identifies recurrent mutations in hepatocellular carcinoma

被引：423

作者：

Kan, Zhengyan ^{[1
]}

Zheng, Hancheng ^{[2
]}

Liu, Xiao ^{[2
,3
]}

Li, Shuyu ^{[4
]}

Barber, Thomas D. ^{[4
]}

Gong, Zhuolin ^{[2
]}

Gao, Huan ^{[2
]}

Hao, Ke ^{[5
]}

Willard, Melinda D. ^{[4
]}

Xu, Jiangchun ^{[1
]}

Hauptschein, Robert ^{[1
]}

Rejto, Paul A. ^{[1
]}

Fernandez, Julio ^{[1
]}

Wang, Guan ^{[2
]}

Zhang, Qinghui ^{[2
]}

Wang, Bo ^{[2
]}

Chen, Ronghua ^{[5
]}

Wang, Jian ^{[4
]}

Lee, Nikki P. ^{[6
]}

Zhou, Wei ^{[5
]}

Lin, Zhao ^{[2
]}

Peng, Zhiyu ^{[2
]}

Yi, Kang ^{[2
]}

Chen, Shengpei ^{[2
]}

Li, Lin ^{[2
]}

Fan, Xiaomei ^{[2
]}

Yang, Jie ^{[2
]}

Ye, Rui ^{[2
]}

Ju, Jia ^{[2
]}

Wang, Kai ^{[1
]}

Estrella, Heather ^{[1
]}

Deng, Shibing ^{[1
]}

Wei, Ping ^{[1
]}

Qiu, Ming ^{[1
]}

Wulur, Isabella H. ^{[4
]}

Liu, Jiangang ^{[4
]}

Ehsani, Mariam E. ^{[4
]}

Zhang, Chunsheng ^{[5
]}

Loboda, Andrey ^{[5
]}

Sung, Wing Kin ^{[6
,7
]}

Aggarwal, Amit

Poon, Ronnie T. ^{[6
]}

Fan, Sheung Tat ^{[6
]}

Wang, Jun ^{[2
,3
,8
,9
]}

Hardwick, James ^{[5
,10
]}

Reinhard, Christoph ^{[4
]}

Dai, Hongyue ^{[5
]}

Li, Yingrui ^{[2
]}

Luk, John M. ^{[6
,11
,12
,13
]}

Mao, Mao ^{[1
,10
]}

机构：

[1] Pfizer Oncol, San Diego, CA 92121 USA

[2] BGI Shenzhen, Shenzhen 518083, Peoples R China

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

[4] Eli Lilly & Co, Indianapolis, IN 46285 USA

[5] Merck Res Labs, Boston, MA 02115 USA

[6] Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China

[7] Natl Univ Singapore, Sch Comp, Singapore 117417, Singapore

[8] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark

[9] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia

[10] Asian Canc Res Grp Inc, Wilmington, DE 19808 USA

[11] Natl Univ Singapore, Dept Pharmacol, Singapore 117597, Singapore

[12] Natl Univ Singapore, Dept Surg, Singapore 117597, Singapore

[13] ASTAR, Inst Mol & Cell Biol, Singapore 138673, Singapore

来源：

GENOME RESEARCH | 2013年 / 23卷 / 09期

关键词：

SOMATIC MUTATIONS; FREQUENT MUTATION; COPY-NUMBER; CANCER; GENE; INHIBITOR; JAK1; SUPPRESSION; ACTIVATION; DISCOVERY;

D O I：

10.1101/gr.154492.113

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide and has no effective treatment, yet the molecular basis of hepatocarcinogenesis remains largely unknown. Here we report findings from a whole-genome sequencing (WGS) study of 88 matched HCC tumor/normal pairs, 81 of which are Hepatitis B virus (HBV) positive, seeking to identify genetically altered genes and pathways implicated in HBV-associated HCC. We find beta-catenin to be the most frequently mutated oncogene (15.9%) and TP53 the most frequently mutated tumor suppressor (35.2%). The Wnt/beta-catenin and JAK/STAT pathways, altered in 62.5% and 45.5% of cases, respectively, are likely to act as two major oncogenic drivers in HCC. This study also identifies several prevalent and potentially actionable mutations, including activating mutations of Janus kinase 1 (JAK1), in 9.1% of patients and provides a path toward therapeutic intervention of the disease.

引用

页码：1422 / 1433

页数：12

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