[Relationship between mutation of tumor suppressor gene p53 and development of hepatocellular carcinoma]

Fourty-five cases of primary hepatocellular carcinoma (PHC) from areas of low aflatoxin B1 exposure but high risk of hepatitis B (HBV) were examined. Positive cases of HBV-DNA were determined in 40 of 45 cases by southern hybridization and polymerase chain reaction (PCR). Results of restriction fragment length polymorphism (RFLP) analysis showed that 1 of 33 informative cases revealed loss of heterozygosity at p53 gene locus. The point mutation of p53 exon 7 was detected by PCR and restriction enzyme digestion with RsaI, MspI and HaeIII, respectively. Only two of the 45 cases showed point mutation on codon 247 and 249, and sequence analysis showed that the changes were C-->G and G-->T, respectively. Frozen section examinations in 1 of 5 cases showed weak positive staining on nucleus by immunohistochemistry with anti-p53 monoclonal antibody (pAb1801). Our results provide evidence suggesting that HBV infection alone do not contribute to changes of p53 gene including allelic loss and point mutation. A multiple step process may exist and multiple genes may be involved in hepatocarcinogenesis.