title: Association of TP53 mutations with stem cell-like gene expression and survival of patients with hepatocellular carcinoma.
abstract: OBJECTIVE
  Mutations in TP53, a tumor suppressor gene, are associated with prognosis of many cancers. However, the prognostic values of TP53 mutation sites are not known for patients with hepatocellular carcinoma (HCC) because of heterogeneity in their geographic and etiologic backgrounds.
  
  
  METHODS
  TP53 mutations were investigated in a total of 409 HCC patients, including Chinese (n = 336) and white (n = 73) patients, using the direct sequencing method.
  
  
  RESULTS
  A total of 125 TP53 mutations were found in Chinese patients with HCC (37.2%). HCC patients with TP53 mutations had a shorter overall survival time compared with patients with wild-type TP53 (hazard ratio [HR], 1.86; 95% confidence interval [CI]: 1.37-2.52; P < .001). The hot spot mutations R249S and V157F were significantly associated with worse prognosis in univariate (HR, 2.11; 95% CI: 1.51-2.94; P < .001) and multivariate analyses (HR, 1.79; 95% CI: 1.29-2.51; P < .001). Gene expression analysis revealed the existence of stem cell-like traits in tumors with TP53 mutations. These findings were validated in breast and lung tumor samples with TP53 mutations.
  
  
  CONCLUSIONS
  TP53 mutations, particularly the hot spot mutations R249S and V157F, are associated with poor prognosis for patients with HCC. The acquisition of stem cell-like gene expression traits might contribute to the aggressive behavior of tumors with TP53 mutation.
authors.affiliation: Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Hyun Goo
authors.initials: HG
authors.lastname: Woo
authors.forename: Xin Wei
authors.initials: XW
authors.lastname: Wang
authors.forename: Anuradha
authors.initials: A
authors.lastname: Budhu
authors.forename: Yun Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: So Mee
authors.initials: SM
authors.lastname: Kwon
authors.forename: Zhao-You
authors.initials: ZY
authors.lastname: Tang
authors.forename: Zongtang
authors.initials: Z
authors.lastname: Sun
authors.forename: Curtis C
authors.initials: CC
authors.lastname: Harris
authors.forename: Snorri S
authors.initials: SS
authors.lastname: Thorgeirsson
mesh_terms: D044466:Asian People / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000208:ethnology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D014411:Neoplastic Stem Cells / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53