[Co-inactivation of the p53 and RB genes in human hepato cellular carcinoma].

Aberrations of the p53 gene were observed in high frequency in HCCs in China, Mozambique and Japan. Most of the mutations were G to T transversions in codon 249 of the p53 gene in HCCs in China and Mozambique, where aflatoxin B1 was a risk factor. These findings strongly suggest that aflatoxin B1 induced this type of mutations. On the other hand, in Japanese HCCs, no mutation was observed in codon 249, indicating a different cause of HCC development. Pathological analyses revealed that p53 mutations were detected only in advanced HCCs and not in early HCCs. In addition, aberrations of the RB gene were observed in only tumors carrying mutated p53 gene. These results indicate the involvement of at least two tumor suppressor genes in a late stage of hepatocarcinogenesis. Possible mechanisms of HCC formation are discussed.