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 possible role of p53 mutations in their genesis, we amplified and sequenced exons 5 to 8 of the p53 gene in 10 cases of hepatoblastoma. Somatic mutations were detected in 9 cases, in eight of which a common point mutation at the first-base position of codon 157 was found, resulting in an amino-acid substitution of phenylalanine for valine. Two missense mutations in codon 244, and one each in codons 273 and 279, were also found, with 3 hepatoblastomas having double mis-sense mutations. Out 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 transcribed strand. Furthermore, p53 over-expression was immunohistochemically observed in 7 out of 9 cases with p53 gene mutations, although the staining pattern was focal and heterogeneous. The findings suggest that particular 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 disease.