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