p53 gene mutations and 17p allelic deletions in hepatocellular carcinoma from Japan.
BACKGROUND: p53 gene mutations at codon 249 have been reported in hepatocellular carcinoma (HCC) from China and South Africa, a phenomenon shown to be closely associated with food contamination by aflatoxin. There have been few reports, however, in regard to p53 gene mutations in HCC from other geographic areas. METHODS: The authors analyzed 20 HCC from Japan for alteration of the p53 gene by restriction fragment length polymorphisms and for nucleic acid mutations by polymerase chain reaction with direct sequencing. RESULTS: Alterations associated with the p53 gene were found in 6 of 20 HCC (30%). Allelic loss of chromosome 17p occurred in 5 of 14 informative (heterozygous) cases (36%). Mutations in the p53 gene were detected in three cases (15%), at codons 176 (exon 5), 236 (exon 7), and 294 (exon 8). These cases were different from the HCC cases from China and South Africa, where point mutations in the p53 gene were reported at the same codon 249 in half of the cases and where aflatoxin food contamination and hepatitis B virus infection are recognized risk factors of HCC. No p53 gene alterations were found in smaller HCC (< 3 cm) or at earlier stages. CONCLUSIONS: In Japan, p53 gene alterations seem to be a late event in the progression of hepatocarcinogenesis, which is often associated with persistent infection by the hepatitis C or B virus, but not usually with exposure to aflatoxin.