title: Mutations acquired by hepatocellular carcinoma recurrence give rise to an aggressive phenotype.
abstract: Recurrence of hepatocellular carcinoma (HCC) even after curative resection causes dismal outcomes of patients. Here, to delineate the driver events of genomic and transcription alteration during HCC recurrence, we performed RNA-Seq profiling of the paired primary and recurrent tumors from two patients with intrahepatic HCC. By comparing the mutational and transcriptomic profiles, we identified somatic mutations acquired by HCC recurrence including novel mutants of GOLGB1 (E2721V) and SF3B3 (H804Y). By performing experimental evaluation using siRNA-mediated knockdown and overexpression constructs, we demonstrated that the mutants of GOLGB1 and SF3B3 can promote cell proliferation, colony formation, migration, and invasion of liver cancer cells. Transcriptome analysis also revealed that the recurrent HCCs reprogram their transcriptomes to acquire aggressive phenotypes. Network analysis revealed CXCL8 (IL-8) and SOX4 as common downstream targets of the mutants. In conclusion, we suggest that the mutations of GOLGB1 and SF3B3 are potential key drivers for the acquisition of an aggressive phenotype in recurrent HCC.
authors.affiliation: Department of Physiology, Ajou University School of Medicine, Suwon, Korea.|Department of Biomedical Science, Graduate School, Ajou University, Suwon, Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Physiology, Ajou University School of Medicine, Suwon, Korea.|Department of Biomedical Science, Graduate School, Ajou University, Suwon, Korea.
authors.forename: Min Jae
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Surgery, Catholic Kwandong University International St. Mary's Hospital, Incheon, Korea.
authors.forename: Yong Keun
authors.initials: YK
authors.lastname: Park
authors.affiliation: Department of Physiology, Ajou University School of Medicine, Suwon, Korea.|Department of Biomedical Science, Graduate School, Ajou University, Suwon, Korea.
authors.forename: Jong-Yeop
authors.initials: JY
authors.lastname: Im
authors.affiliation: Department of Physiology, Ajou University School of Medicine, Suwon, Korea.|Department of Biomedical Science, Graduate School, Ajou University, Suwon, Korea.
authors.forename: So Mee
authors.initials: SM
authors.lastname: Kwon
authors.affiliation: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Hyung Chul
authors.initials: HC
authors.lastname: Kim
authors.affiliation: Department of Physiology, Ajou University School of Medicine, Suwon, Korea.|Department of Biomedical Science, Graduate School, Ajou University, Suwon, Korea.
authors.forename: Hyun Goo
authors.initials: HG
authors.lastname: Woo
authors.affiliation: Department of Surgery, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Wang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D014162:Transfection
keywords: GOLGB1; RNA-Seq; SF3B3; mutation; recurrence