title: p53 overexpression is frequent in European hepatocellular carcinoma and largely independent of the codon 249 hot spot mutation.
abstract: Mutations in the p53 tumour suppressor gene have been recently described in hepatocellular carcinomas (HCC) from high risk areas such as China and South Africa. Our study was designed to assess the importance of p53 aberrations in HCCs from Europe, where the major risk factors in hepatocarcinogenesis, aflatoxin exposure and chronic hepatitis B virus (HBV) infection, do not play a dominant role. We investigated 22 HCCs and, as controls, their corresponding tumour-free liver tissues, seven livers with primary biliary cirrhosis and four morphologically normal livers. p53 overexpression, which is usually associated with point mutations of the p53 gene, was detected in 10 of the 22 HCCs by immunoblotting and immunohistochemistry. p53 expression was restricted to the nucleus in the positive cells, while all cells in the control tissues were negative. There was no obvious etiological preference in the p53 positive tumours. Particularly, underlying chronic HBV infection did not appear to be associated with an increased rate of p53 overexpression in European HCCs. SSCP and sequence analysis of exons 5-8 of the p53 gene revealed point mutations in six out of eight tumours with increased steady state levels of p53. In conclusion, our study demonstrates increased p53 levels due to point mutations in a significant proportion of European HCCs. The codon 249 mutation, which was detected in one of the cases, is not predominant in these tumours.
authors.affiliation: Deutsches Krebsforschungszentrum-Angewandte Tumorvirologie, Heidelberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Volkmann
authors.forename: W J
authors.initials: WJ
authors.lastname: Hofmann
authors.forename: M
authors.initials: M
authors.lastname: Müller
authors.forename: U
authors.initials: U
authors.lastname: Räth
authors.forename: G
authors.initials: G
authors.lastname: Otto
authors.forename: H
authors.initials: H
authors.lastname: Zentgraf
authors.forename: P R
authors.initials: PR
authors.lastname: Galle
mesh_terms: D000328:Adult; D000348:Aflatoxins / Q000633:toxicity; D000368:Aged; D001483:Base Sequence; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003062:Codon; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D016158:Genes, p53; D006801:Humans; D008099:Liver / Q000737:chemistry; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017354:Point Mutation; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: D000348:Aflatoxins; D003062:Codon; D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53