[Aberrations of tumor suppressor genes in hepatocellular carcinomas]

Mutation of the p53 gene and loss of heterozygosity of the p53, Rb, APC, and MCC genes were examined in 14 hepatocellular carcinomas (HCCs) diagnosed at the third department of internal medicine in Asahikawa Medical College. Mutations in the p53 gene were detected in 4 HCCs out of 14 (25%) using polymerase chain reaction-single strand conformational polymorphism. The sites of the mutations showed a random distribution from exon 6 to 8. No mutation was observed at codon 249, which has been considered as a mutational hot spot caused by aflatoxin B1. All of the mutations occurred at a G:C base pair site, while two mutations were C:G to T:A transitions and other two mutations were G:C to T:A transversions. Pathological examination showed that the 14 HCCs consisted of 7 moderately and 7 poorly differentiated HCCs. All of the 4 HCCs which showed mutations were poorly differentiated and the frequency of the mutations were 0% in moderately and 57% in poorly differentiated HCCs. Loss of heterozygosity of the p53, Rb and APC genes were examined in the 14 HCCs using restriction fragment length polymorphism analysis. Frequencies of the loss of the p53, Rb, APC, and MCC genes were 2 out of 7 informative cases (2/7), 1/6, 0/4, and 0/7, respectively. Frequency of loss of the p53 gene in four HCCs carrying a mutated p53 gene was 1/3. These data suggest that inactivation of the p53 gene is involved in human hepatocarcinogenesis, but the APC/MCC genes are not.