Mutation of tumor suppressor gene p53 in hepatocellular carcinomas from Korea

Mutation of the p53 gene in hepatocellular carcinoma has been recognized as one of the most important genetic alterations to occur during hepatocarcinogenesis. This study was performed to analyze the frequency and nature of p53 mutations in advanced hepatocellular carcinomas from Korea. Tissue samples were obtained by laparoscopic biopsy from 35 patients; adjacent nontumorous liver tissue was also obtained from 24 of them. Mutations of the p53 gene were identified in 11/35 (31%) of hepatocellular carcinomas, These included 7 missense mutations and 4 deletion mutations. Only one mutation was detected at codon 249, a ''hot spot'' at which mutations have been found frequently in hepatocellular carcinomas from some geographic areas; however, this was an A-to-T transversion at the first nucleotide, thus differing from commonly reported G-to-T transversion at the third nucleotide of codon 249 in hepatocellular carcinomas, Patients whose serum alkaline phosphatase levels were higher than the mean Value were more likely to have p53 mutations, compared to patients whose alkaline phosphatase levels were lower than the mean value [55% (6/11) vs. 21% (5/24)] (p<0.05). Thus, p53 mutations are found in many hepatocellular carcinomas in Korea. However, mutations commonly thought to be due to aflatoxin B-1 (G-to-T transversion at codon 249) were not found, suggesting that aflatoxin-B-1 does not play an important role in the etiology of hepatocellular carcinoma in Korea.