Abstract
We investigated the association between human papillomavirus (HPV) infection and p53 gene mutation in 47 primary uterine cervical cancers. HPV DNA sequences were present in 43 cancers (91.5%), and one of these cancers contained a p53 gene mutation. In addition, one of the remaining four HPV-negative cancers also contained a p53 gene mutation. As a result, p53 inactivation corresponded to the development of 44 of the primary uterine cervical cancers studied (93.6%). We obtained both primary and recurrent tumours from four cases. In two of these cases, the HPV genomes that were present in an episomal state in the primary tumours were observed to have disappeared in the recurrent tumours. One of these recurrent tumours also contained a p53 gene mutation, which suggested the possibility that p53 inactivation was required in order to maintain the aggressive behaviour in this cancer either by an HPV infection or by a p53 gene mutation. No MDM2 gene amplification was observed in the tumours that carried neither HPV DNAs nor p53 gene mutations.
MeSH terms
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Adenocarcinoma / genetics
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Adenocarcinoma / pathology
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Adenocarcinoma / virology
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Base Sequence
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Blotting, Southern
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Carcinoma, Squamous Cell / genetics*
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Carcinoma, Squamous Cell / pathology
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Carcinoma, Squamous Cell / virology
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Cell Transformation, Neoplastic / genetics*
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Cell Transformation, Viral / genetics
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Cocarcinogenesis*
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DNA Mutational Analysis
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DNA Probes, HPV
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DNA, Viral / genetics
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Female
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Gene Amplification
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Gene Expression Regulation, Neoplastic
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Gene Expression Regulation, Viral
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Genes, p53*
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Humans
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Molecular Sequence Data
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Neoplasm Proteins / genetics*
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Neoplasm Proteins / physiology
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Neoplasm Recurrence, Local / genetics
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Neoplasm Recurrence, Local / pathology
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Neoplasm Recurrence, Local / virology
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Nuclear Proteins*
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Oncogene Proteins, Viral / physiology
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Papillomaviridae / genetics
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Papillomaviridae / isolation & purification*
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Papillomaviridae / pathogenicity
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Papillomavirus Infections / genetics*
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Papillomavirus Infections / pathology
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Polymerase Chain Reaction
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / physiology*
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Proto-Oncogene Proteins c-mdm2
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Tumor Virus Infections / genetics*
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Tumor Virus Infections / pathology
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Uterine Cervical Neoplasms / genetics*
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Uterine Cervical Neoplasms / pathology
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Uterine Cervical Neoplasms / virology
Substances
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DNA Probes, HPV
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DNA, Viral
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Neoplasm Proteins
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Nuclear Proteins
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Oncogene Proteins, Viral
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Proto-Oncogene Proteins
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MDM2 protein, human
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Proto-Oncogene Proteins c-mdm2