New p53 mutations in hilar cholangiocarcinoma

Background inactivation of the tumour suppressor gene, p53, is the commones t genetic abnormality in human cancer. The study of the type of p53 mutatio n in a given tumour may provide prognostic information, clues to aetiology and become useful for therapeutics. Materials and Methods The molecular characterisation of p53 was performed b y restriction analysis, denaturing gradient gel electrophoresis, and gene s equencing for exons 5-9. Results We report, p53 mutational analysis in exons 5-9 in 29 European pati ents with hilar cholangiocarcinoma who underwent attempted resection. Four patients (14%) showed somatic single nucleotide substitutions with amino ac id 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 o ccurred 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 patt ern previously reported for intrahepatic cholangiocarcinoma in East Asian p atients. A probable explanation is that the presence and type of p53 mutati on is dependent on geographic and environmental factors which vary in diffe rent populations.