A MUTATIONAL HOT-SPOT IN THE P53 GENE IS ASSOCIATED WITH HEPATOBLASTOMAS

Hepatoblastomas generally appear in children aged 2 or 3 years old and arise from apparently normal, non-cirrhotic liver. To elucidate any p ossible role of p53 mutations in their genesis, we amplified and seque nced exons 5 to 8 of the p53 gene in 10 cases of hepatoblastoma. Somat ic mutations were detected in 9 cases, in eight of which a common poin t mutation at the first-base position of codon 157 was found, resultin g in an amino-acid substitution of phenylalanine for valine. Two misse nse mutations in codon 244, and one each in codons 273 and 279, were a lso found, with 3 hepatoblastomas having double mis-sense mutations. O ut of the total of 12 mutations, 11 were G-to-T transversions. One was a G-to-A transition and guanines were always present on the transcrib ed strand. Furthermore, p53 over-expression was immunohistochemically observed in 7 out of 9 cases with p53 gene mutations, although the sta ining pattern was focal and heterogeneous. The findings suggest that p articular environmental mutagens may be involved in mutagenesis of the p53 gene in some cases of hepatoblastomas and that p53 mutations at a specific site may play an important role in the genesis of this disea se. (C) 1995 Wiley-Liss, Inc.