Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa.
Hepatocellular carcinoma (HCC) is a prevalent cancer in sub-Saharan Africa and eastern Asia. Hepatitis B virus and aflatoxins are risk factors for HCC, but the molecular mechanism of human hepatocellular carcinogenesis is largely unknown. Abnormalities in the structure and expression of the tumour-suppressor gene p53 are frequent in HCC cell lines, and allelic losses from chromosome 17p have been found in HCCs from China and Japan. Here we report on allelic deletions from chromosome 17p and mutations of the p53 gene found in 50% of primary HCCs from southern Africa. Four of five mutations detected were G----T substitutions, with clustering at codon 249. This mutation specificity could reflect exposure to a specific carcinogen, one candidate being aflatoxin B1 (ref. 7), a food contaminant in Africa, which is both a mutagen that induces G to T substitution and a liver-specific carcinogen.
Bressac
B
B
Molecular Hepatology Laboratory, Massachusetts General Hospital Cancer Center, Charlestown 02129.
Kew
M
M
Wands
J
J
Ozturk
M
M
D000348:Aflatoxins / Q000633:toxicity; D000353:Africa, Southern; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D015342:DNA Probes; D005091:Exons; D016147:Genes, Tumor Suppressor; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009841:Oligonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D000348:Aflatoxins; D015342:DNA Probes; D009841:Oligonucleotides; D016159:Tumor Suppressor Protein p53