Whole genome sequencing identifies recurrent mutations in hepatocellular carcinoma
- Zhengyan Kan1,
- Hancheng Zheng2,
- Xiao Liu2,
- Shuyu Li3,
- Thomas Barber3,
- Zhuolin Gong2,
- Huan Gao2,
- Ke Hao4,
- Melinda D Willard3,
- Jiangchun Xu1,
- Robert Hauptschein1,
- Paul A Rejto1,
- Julio Fernandez1,
- Guan Wang2,
- Qinghui Zhang2,
- Bo Wang2,
- Ronghua Chen4,
- Jian Wang3,
- Nikki P Lee5,
- Wei Zhou4,
- Zhao Lin2,
- Zhiyu Peng2,
- Kang Yi2,
- Shengpei Chen2,
- Lin Li2,
- Xiaomei Fan2,
- Jie Yang2,
- Rui Ye2,
- Jia Ju2,
- Kai Wang1,
- Heather Estrella1,
- Shibing Deng1,
- Ping Wei1,
- Ming Qiu1,
- Isabella H Wulur3,
- Jiangang Liu3,
- Mariam E Ehsani3,
- Chunsheng Zhang4,
- Andrey Loboda4,
- Wing Kin Sung6,
- Amit Aggarwal3,
- Ronnie T Poon5,
- Sheung Tat Fan5,
- James Hardwick4,
- Jun Wang2,
- Christoph Reinhard3,
- Hongyue Dai4,
- Yingrui Li2,
- John M Luk5 and
- Mao Mao1,7
- 1 Pfizer Oncology;
- 2 BGI-Shenzhen;
- 3 Eli Lilly and Company;
- 4 Merck Research Laboratories;
- 5 University of Hong Kong;
- 6 National University of Singapore
- ↵* Corresponding author; email: mao.mao{at}pfizer.com
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 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 towards therapeutic intervention of the disease.
- Received January 4, 2013.
- Accepted June 17, 2013.
- © 2013, Published by Cold Spring Harbor Laboratory Press
This manuscript is Open Access.
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.
