title: Exome sequencing of hepatitis B virus-associated hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and shows a propensity to metastasize and infiltrate adjacent and more distant tissues. HCC is associated with multiple risk factors, including hepatitis B virus (HBV) infection, which is especially prevalent in China. Here, we used exome sequencing to identify somatic mutations in ten HBV-positive individuals with HCC with portal vein tumor thromboses (PVTTs), intrahepatic metastases. Both C:G>A:T and T:A>A:T transversions were frequently found among the 331 non-silent mutations. Notably, ARID1A, which encodes a component of the SWI/SNF chromatin remodeling complex, was mutated in 14 of 110 (13%) HBV-associated HCC specimens. We used RNA interference to assess the roles of 91 of the confirmed mutated genes in cellular survival. The results suggest that seven of these genes, including VCAM1 and CDK14, may confer growth and infiltration capacity to HCC cells. This study provides a view of the landscape of somatic mutations that may be implicated in advanced HCC.
authors.affiliation: Human Genome Center of Rui-Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.forename: Qing
authors.initials: Q
authors.lastname: Deng
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: Kun-Yu
authors.initials: KY
authors.lastname: Li
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Dai
authors.forename: Niu
authors.initials: N
authors.lastname: Li
authors.forename: Zhi-Dong
authors.initials: ZD
authors.lastname: Zhu
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Liu
authors.forename: Rui-Fang
authors.initials: RF
authors.lastname: Liu
authors.forename: Qian-Lan
authors.initials: QL
authors.lastname: Fei
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Bing
authors.initials: B
authors.lastname: Cai
authors.forename: Boping
authors.initials: B
authors.lastname: Zhou
authors.forename: Hua-Sheng
authors.initials: HS
authors.lastname: Xiao
authors.forename: Lun-Xiu
authors.initials: LX
authors.lastname: Qin
authors.forename: Ze-Guang
authors.initials: ZG
authors.lastname: Han
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000556:secondary / Q000821:virology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D041321:Chromosomes, Human, X / Q000235:genetics; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D004268:DNA-Binding Proteins; D059472:Exome; D005260:Female; D056726:Genetic Association Studies; D006509:Hepatitis B / Q000150:complications*; D006515:Hepatitis B virus; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011169:Portal Vein / Q000473:pathology; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics; D020246:Venous Thrombosis / Q000235:genetics / Q000821:virology
chemical_list: C112476:ARID1A protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D019010:Vascular Cell Adhesion Molecule-1; C515076:CDK14 protein, human; D018844:Cyclin-Dependent Kinases