Analysis of the p53 tumor-suppressor gene in hepatocellular carcinomas from britain

Authors

  • Christine Challen,

    1. Medical Molecular Biology Group, Department of Medicine, The Medical School, Newcastle upon Tyne, NE2 4HH
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  • John Lunec,

    1. Cancer Research Unit, The Medical School, Newcastle upon Tyne, NE2 4HH
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  • William Warren,

    1. Institute of Cancer Research, The Haddow Laboratories, Surrey, SM2 5NG, United Kingdom
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  • Jane Collier,

    1. Medical Molecular Biology Group, Department of Medicine, The Medical School, Newcastle upon Tyne, NE2 4HH
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  • Dr. Margaret F. Bassendine

    Corresponding author
    1. Medical Molecular Biology Group, Department of Medicine, The Medical School, Newcastle upon Tyne, NE2 4HH
    • University of Newcastle upon Tyne, Medical Molecular Biolog Group, Floor 4-Catherine Cookson Building, The Medical School, Framlington Place, Newcastle upon Tyne, NE2 4HH, United Kingdom
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Abstract

Human hepatocellular carcinomas from patients in Britain, an area of low prevalence of hepatocellular carcinoma and low dietary exposure to aflatoxin B1, were analyzed for mutations in the p53 tumorsuppressor gene. Abnormalities in the p53 gene were detected in 2 of 19 hepatocellular carcinomas by polymerase chain reaction—single-stranded conformation polymorphism. Direct sequencing of the evolutionarily conserved regions of p53 (exons 5,6,7 and 8), where mutations have been commonly found in a variety of tumors, confirmed that only two hepatocellular carcinomas had mutations in p53, one a 6-bp deletion of codons 158 and 159 (exon 5) and the other a G to A transition at codon 286 (exon 8). No mutations were found in any hepatocellular carcinoma in exons 6 and 7; in particular all tumors had wild-type sequence at codon 249, which has been reported to be a mutational hot spot in the p53 gene in hepatocellular carcinomas from high incidence areas such as China and southern Africa. Abnormalities in p53 expression were examined by immunohistochemistry and found in 1 of the 19 hepatocellular carcinomas. These findings show that p53 mutations are infrequently involved in the malignant transformation of hepatocytes in an area of low hepatocellular carcinoma prevalence. They support the suggestion of a possible link between dietary exposure to aflatoxin and selective G to T mutations at codon 249 of the p53 gene. Our observations also indicate that hepatitis B virus infection alone, present in six of the hepatocellular carcinomas examined, does not account for the specificity for codon 249 mutations reported from endemic areas.

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