Abstract
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) v s. 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 B1 (G-to-T transversion at codon 249) were not found, suggesting that aflatoxin-B1 does not play an important role in the etiology of hepatocellular carcinoma in Korea.
Highlights
Hepatocellular carcinoma is one of the most common cancers in the world
Chronic infection with hepatitis B virus and hepatitis C virus are important etiologic factors for the development of hepatocellular carcinoma, but it is possible that other factors such as chemical carcinogens may contribute to carcinogenesis
A mutation at p53 codon 249 with a G-to-T transversion at the third nucleotide has been found frequently in hepatocellular carcinomas from southern Africa and Qidong, China, areas in which dietary aflatoxin B1 may play an important role in the etiology of hepatocellular carcinoma (Hsu et al, 1991; Bressac et al, 1991; Ozturk et al, 1991)
Summary
Hepatocellular carcinoma is one of the most common cancers in the world. Chronic infection with hepatitis B virus and hepatitis C virus are important etiologic factors for the development of hepatocellular carcinoma, but it is possible that other factors such as chemical carcinogens may contribute to carcinogenesis. The tumor suppressor gene p53 has been found to be commonly mutated in various human tumors including hepatocellular carcinoma (Nigro et al, 1989; Levine et al ., 1991; Hollstein et al ., 1991; Harris and Hollstein, 1993). Hepatocellular carcinomas from geographic areas where aflatoxin is uncommon in the diet do not have such a mutational “hot spot” for p53 (Ozturk et al, 1991; Unsal et al , 1994). These observations indicate that the molecular mechanisms of p53 gene damage or dysfunction in hepatocarcinogenesis may be heterogeneous. Exons 3 to 9 of the p53 gene were investigated to determine the frequency, nature, and significance of mutations in these genes in advanced hepatocellular carcinomas from Korea
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