title: Whole-genome sequencing identifies recurrent mutations in hepatocellular carcinoma.
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.
authors.affiliation: Pfizer Oncology, San Diego, California 92121, USA.
authors.forename: Zhengyan
authors.initials: Z
authors.lastname: Kan
authors.forename: Hancheng
authors.initials: H
authors.lastname: Zheng
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.forename: Shuyu
authors.initials: S
authors.lastname: Li
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Barber
authors.forename: Zhuolin
authors.initials: Z
authors.lastname: Gong
authors.forename: Huan
authors.initials: H
authors.lastname: Gao
authors.forename: Ke
authors.initials: K
authors.lastname: Hao
authors.forename: Melinda D
authors.initials: MD
authors.lastname: Willard
authors.forename: Jiangchun
authors.initials: J
authors.lastname: Xu
authors.forename: Robert
authors.initials: R
authors.lastname: Hauptschein
authors.forename: Paul A
authors.initials: PA
authors.lastname: Rejto
authors.forename: Julio
authors.initials: J
authors.lastname: Fernandez
authors.forename: Guan
authors.initials: G
authors.lastname: Wang
authors.forename: Qinghui
authors.initials: Q
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Ronghua
authors.initials: R
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Nikki P
authors.initials: NP
authors.lastname: Lee
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Zhao
authors.initials: Z
authors.lastname: Lin
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Peng
authors.forename: Kang
authors.initials: K
authors.lastname: Yi
authors.forename: Shengpei
authors.initials: S
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Fan
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Rui
authors.initials: R
authors.lastname: Ye
authors.forename: Jia
authors.initials: J
authors.lastname: Ju
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Heather
authors.initials: H
authors.lastname: Estrella
authors.forename: Shibing
authors.initials: S
authors.lastname: Deng
authors.forename: Ping
authors.initials: P
authors.lastname: Wei
authors.forename: Ming
authors.initials: M
authors.lastname: Qiu
authors.forename: Isabella H
authors.initials: IH
authors.lastname: Wulur
authors.forename: Jiangang
authors.initials: J
authors.lastname: Liu
authors.forename: Mariam E
authors.initials: ME
authors.lastname: Ehsani
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Andrey
authors.initials: A
authors.lastname: Loboda
authors.forename: Wing Kin
authors.initials: WK
authors.lastname: Sung
authors.forename: Amit
authors.initials: A
authors.lastname: Aggarwal
authors.forename: Ronnie T
authors.initials: RT
authors.lastname: Poon
authors.forename: Sheung Tat
authors.initials: ST
authors.lastname: Fan
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: James
authors.initials: J
authors.lastname: Hardwick
authors.forename: Christoph
authors.initials: C
authors.lastname: Reinhard
authors.forename: Hongyue
authors.initials: H
authors.lastname: Dai
authors.forename: Yingrui
authors.initials: Y
authors.lastname: Li
authors.forename: John M
authors.initials: JM
authors.lastname: Luk
authors.forename: Mao
authors.initials: M
authors.lastname: Mao
mesh_terms: D000595:Amino Acid Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D015894:Genome, Human; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D053613:Janus Kinase 1 / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D050791:STAT Transcription Factors / Q000235:genetics; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D016662:Virus Integration; D060449:Wnt Signaling Pathway / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
chemical_list: D004279:DNA, Viral; D050791:STAT Transcription Factors; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; C507904:JAK1 protein, human; D053613:Janus Kinase 1