TP53 and hepatocellular carcinoma.
TP53 gene mutations occur in 30 to 55% hepatocellular carcinomas. Both the frequency and the type of p53 mutations in HCC vary according to geographical location of tumors. A specific mutation at codon 249 (AGG-->AGT) was found at high frequency in tumors from high aflatoxin-areas. TP53 mutations in other geographic locations are less frequent and scattered on the exons encoding the central region of the protein. TP53 mutations observed in hepatocellular carcinoma are accompanied by a loss of wild-type p53 function. Moreover, the p53-249ser mutant appears to display a gain of function at some degree. In addition to p53 inactivation by gene mutation, there is growing evidence that the wild-type p53 functions can be inactivated by the HBx protein of Hepatitis B Virus. The hepatocellular functions of wild-type p53 protein are not entirely known. The present data suggest that the DNA damaging agents induce p53-dependent cell cycle arrest or apoptosis in cell lines derived from normal liver or hepatocellular carcinoma. In contrast, the exposure of mice to genotoxic agents does not induce p53-dependent changes in normal adult liver. This could be due to the fact that the hepatocytes of the adult liver are quiescent cells.
Puisieux
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A
Unité INSERM U453, Centre Léon, Bérard, Lyon, France.
Ozturk
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M
D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D016158:Genes, p53; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics*; D009154:Mutation; D012016:Reference Values