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

共 66 条

[61] Mutational analysis of JAK1 gene in human hepatocellular carcinoma
Xie, H. J.
Bae, H. J.
Noh, J. H.
Eun, J. W.
Kim, J. K.
Jung, K. H.
Ryu, J. C.
Ahn, Y. M.
Kim, S. Y.
Lee, S. H.
Yoo, N. J.
Lee, J. Y.
Park, W. S.
Nam, S. W.
[J]. NEOPLASMA, 2009, 56 (02) : 136 - 140
[62] HDPR1, a novel inhibitor of the WNT/β-catenin signaling, is frequently downregulated in hepatocellular carcinoma:: involvement of methylation-mediated gene silencing
Yau, TO
Chan, CY
Chan, KL
Lee, MF
Wong, CM
Fan, ST
Ng, IOL
[J]. ONCOGENE, 2005, 24 (09) : 1607 - 1614
[63] Clinical significance of high focal adhesion kinase gene copy number and overexpression in invasive breast cancer
Yom, Cha Kyong
Noh, Dong-Young
Kim, Woo Ho
Kim, Hee Sung
[J]. BREAST CANCER RESEARCH AND TREATMENT, 2011, 128 (03) : 647 - 655
[64] Identifying cancer driver genes in tumor genome sequencing studies
Youn, Ahrim
Simon, Richard
[J]. BIOINFORMATICS, 2011, 27 (02) : 175 - 181
[65] Cancer gene discovery in hepatocellular carcinoma
Zender, Lars
Villanueva, Augusto
Tovar, Victoria
Sia, Daniela
Chiang, Derek Y.
Llovet, Josep M.
[J]. JOURNAL OF HEPATOLOGY, 2010, 52 (06) : 921 - 929
[66] Identification of genomic indels and structural variations using split reads
Zhang, Zhengdong D.
Du, Jiang
Lam, Hugo
Abyzov, Alex
Urban, Alexander E.
Snyder, Michael
Gerstein, Mark
[J]. BMC GENOMICS, 2011, 12

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