title: New p53 mutations in hilar cholangiocarcinoma.
abstract: BACKGROUND
  Inactivation of the tumour suppressor gene, p53, is the commonest genetic abnormality in human cancer. The study of the type of p53 mutation in a given tumour may provide prognostic information, clues to aetiology and become useful for therapeutics.
  
  
  METHODS
  The molecular characterisation of p53 was performed by restriction analysis, denaturing gradient gel electrophoresis, and gene sequencing for exons 5-9.
  
  
  RESULTS
  We report, p53 mutational analysis in exons 5-9 in 29 European patients with hilar cholangiocarcinoma who underwent attempted resection. Four patients (14%) showed somatic single nucleotide substitutions with amino acid changes (146, 163, 175, 158, and 175) with one showing mutations in two different positions involving a loss of two CfoI sites. All the mutations occurred in exon 5. Three patients had a germline polymorphism (10%) with a silent substitution in codon 213 (exon 6).
  
  
  CONCLUSIONS
  The systematic screening for p53 mutations in European patients with hilar cholangiocarcinoma has shown that the type of mutation (except 175) is different and its incidence is much lower when compared to the pattern previously reported for intrahepatic cholangiocarcinoma in East Asian patients. A probable explanation is that the presence and type of p53 mutation is dependent on geographic and environmental factors which vary in different populations.
authors.affiliation: CNR Bari, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Tullo
authors.forename: A M
authors.initials: AM
authors.lastname: D'Erchia
authors.forename: K
authors.initials: K
authors.lastname: Honda
authors.forename: M D
authors.initials: MD
authors.lastname: Kelly
authors.forename: N A
authors.initials: NA
authors.lastname: Habib
authors.forename: C
authors.initials: C
authors.lastname: Saccone
authors.forename: E
authors.initials: E
authors.lastname: Sbisà
mesh_terms: D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000235:genetics*; D001653:Bile Ducts, Intrahepatic; D018281:Cholangiocarcinoma / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53