Whole-genome sequencing identifies recurrent mutations in hepatocellular carcinoma

Zhengyan Kan, Hancheng Zheng, Xiao Liu, Shuyu Li, Thomas D. Barber, Zhuolin Gong, Huan Gao, Ke Hao, Melinda D. Willard, Jiangchun Xu, Robert Hauptschein, Paul A. Rejto, Julio Fernandez, Guan Wang, Qinghui Zhang, Bo Wang, Ronghua Chen, Jian Wang, Nikki P. Lee, Wei ZhouZhao Lin, Zhiyu Peng, Kang Yi, Shengpei Chen, Lin Li, Xiaomei Fan, Jie Yang, Rui Ye, Jia Ju, Kai Wang, Heather Estrella, Shibing Deng, Ping Wei, Ming Qiu, Isabella H. Wulur, Jiangang Liu, Mariam E. Ehsani, Chunsheng Zhang, Andrey Loboda, Wing Kin Sung, Amit Aggarwal, Ronnie T. Poon, Sheung Tat Fan, Jun Wang, James Hardwick, Christoph Reinhard, Hongyue Dai, Yingrui Li, John M. Luk, Mao Mao

Research output: Contribution to journalArticlepeer-review

408 Scopus citations

Abstract

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%). TheWnt/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.

Original languageEnglish
Pages (from-to)1422-1433
Number of pages12
JournalGenome Research
Volume23
Issue number9
DOIs
StatePublished - Sep 2013
Externally publishedYes

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