title: Alterations of tumor suppressor genes and allelic losses in human hepatocellular carcinomas in China.
abstract: Aflatoxin B1 has been suggested as a causative agent for a G to T mutation at codon 249 in the p53 gene in human hepatocellular carcinomas (HCC) from southern Africa and Qidong in China. The objective of the present work was to test the hypothesis that exposure to aflatoxin B1 either alone or coincident with other environmental carcinogens might be associated with allelic losses occurring during development of human hepatocarcinogenesis in China. The HCCs were obtained from two different areas in China: Qidong, where exposure to hepatitis B virus (HBV) and aflatoxin B1 is high; and Beijing, where exposure to HBV is high but that of aflatoxin B1 is low. We analyzed the tumors for mutations in the p53 gene and loss of heterozygosity for the p53, Rb, and APC genes and at marker loci on chromosomes 4, 13, and 16. Frequencies of mutation, loss, and aberration (mutation and loss) of the p53 gene in 25 HCCs from Qidong were 60, 58, and 80%, respectively. The frequencies in 9 HCCs from Beijing were 56, 57, and 78%. However, the frequency of a G to T transversion at codon 249 in HCCs from Qidong and Beijing were 52 and 0%, respectively. These data indicate that mutation and/or loss of heterozygosity in the p53 gene, independent of the 249 mutation, play a critical role in the development of hepatitis B virus-associated HCCs in China. Loss of the Rb and APC genes was observed in 44 and 7% of HCCs from Qidong, respectively. Allelic losses on chromosome 4 and especially on chromosome 16 were frequent in HCCs from Qidong but were not observed in HCCs from Beijing, while loss of heterozygosity on chromosome 13 occurred at similar frequency in both Qidong and Beijing. These results show a distinct difference in the pattern of allelic losses between HCCs in Qidong and Beijing and suggest that aflatoxin B1 and/or other environmental carcinogens may contribute to this difference.
authors.affiliation: Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892.
authors.forename: Y
authors.initials: Y
authors.lastname: Fujimoto
authors.forename: L L
authors.initials: LL
authors.lastname: Hampton
authors.forename: P J
authors.initials: PJ
authors.lastname: Wirth
authors.forename: N J
authors.initials: NJ
authors.lastname: Wang
authors.forename: J P
authors.initials: JP
authors.lastname: Xie
authors.forename: S S
authors.initials: SS
authors.lastname: Thorgeirsson
mesh_terms: D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000276:immunology; D002681:China; D002882:Chromosomes, Human, Pair 13; D002885:Chromosomes, Human, Pair 16; D002894:Chromosomes, Human, Pair 4; D003062:Codon / Q000235:genetics; D017353:Gene Deletion; D017491:Genes, APC / Q000235:genetics*; D016161:Genes, Retinoblastoma / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D006511:Hepatitis B Antigens / Q000032:analysis; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D003062:Codon; D006511:Hepatitis B Antigens