title: Transcriptomic characterization of hepatocellular carcinoma with CTNNB1 mutation.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) is the sixth most common solid tumor worldwide and the third leading cause of cancer-related death. HCC is a particularly serious threat to the Chinese population. Although many molecular alterations are known to be involved in the tumorigenesis of hepatocytes, no systemic survey has examined the somatic mutations in HCC samples from Chinese patients. Our goal was to elucidate somatic mutations in Chinese HCC patients and investigate the possible molecular mechanisms involved in tumorigenesis.
  
  
  METHODS
  A total of 110 hepatitis B virus (HBV)-positive HCC samples and 46 HBV-negative HCC samples were genotyped for hot-spot mutations in the CSF1R, CTNNB1, KRAS, BRAF, NRAS, ERBB2, MET, PIK3CA, JAK1, and SMO genes. The transcriptomes of the CTNNB1 mutation-positive HCC samples from the HBV-positive patients (CB+ HCC) were compared to adjacent non-cancerous livers, and significantly altered genes were functionally validated in vitro.
  
  
  RESULTS
  CTNNB1 mutations accounted for the majority of the mutations detected in our study. A slightly higher mutation rate was found in the HBV-positive patients than in their negative counterparts. A distinct pattern of CTNNB1 mutation was detected in these two populations, and drastic changes at the transcriptomic level were detected in the CB+ tumors compared to adjacent non-cancerous livers. Potential tumor suppressors (FoxA3 and Onecut1) and oncogenes (MAFG and SSX1) were functionally validated.
  
  
  CONCLUSIONS
  Our work is the first systemic characterization of oncogenic mutations in HCC samples from Chinese patients. Targeting the Wnt-β-catenin pathway may represent a valid treatment option for Chinese HCC patients. Our work also suggests that targeting ONECUT1, FOXA3, SSX1, and MAFG may be a valid treatment option for CTNNB1 mutation positive HCC patients.
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ding
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Yangpu, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing, China.
authors.forename: Baoda
authors.initials: B
authors.lastname: Han
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing, China.
authors.forename: Chengzhi
authors.initials: C
authors.lastname: Du
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing, China.
authors.forename: Naiqing
authors.initials: N
authors.lastname: Xu
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing, China.
authors.forename: Huanwei
authors.initials: H
authors.lastname: Huang
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Cai
authors.affiliation: The General Hospital of People's Liberation Army (301 Hospital), Beijing, China.
authors.forename: Aiqun
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Ze-Guang
authors.initials: ZG
authors.lastname: Han
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Yangpu, Shanghai, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Collaborative Innovation Center of Cancer Medicine, National Institute of Biological Sciences, Beijing, Beijing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism; D002681:China; D005260:Female; D020869:Gene Expression Profiling; D006509:Hepatitis B / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D059467:Transcriptome / Q000235:genetics*; D060449:Wnt Signaling Pathway / Q000235:genetics; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics
chemical_list: C495270:CTNNB1 protein, human; D009363:Neoplasm Proteins; D051176:beta Catenin