ANALYSIS OF THE P53 GENE IN EUROPEAN HEPATOCELLULAR CARCINOMAS AND HEPATOBLASTOMAS

Human hepatocellular carcinomas (HCC) and hepatoblastomas (HB) from pa tients in France and Italy, respectively, which are both areas with a low incidence of HCC and a low dietary exposure to aflatoxin B1 (AFB1) , were analysed for alterations of the p53 tumour suppressor gene. An abnormality in the p53 gene was detected in only one of the seven HCCs examined. Sequencing of the cDNA of this HCC revealed a G to T transv ersion at the first nucleotide of codon 245 that was not found in norm al tissue, excluding the possibility of germinal transmission of this alteration. All tumours had the wild-type sequence at codon 249, which has been reported to be a mutational hot spot in the p53 gene in HCCs from high incidence areas, such as China and Southern Africa. Seven s amples of HB, the most common hepatic tumour of children, were also te sted for loss of heterozygosity (LOH) and mutations in the p53 gene. I n contrast to what is observed in HCC of adulthood, for which environm ental conditions are important etiological risk factors, HB probably s tems uniquely from genetic disorders. PCR-direct sequencing of exons 4 to 8 and PCR-single strand conformation polymorphism (PCR-SSCP) of ex ons 2, 3 and 9 revealed no mutations in the coding sequences examined. LOH was observed in one of the five informative cases when codon 72 a nd intron 6 were subjected to polymorphism analysis.