Loss of heterozygosity on chromosome 17p and mutant p53 in HPV-negative cervical carcinomas

M. Kaelbling, HaroldP Klinger, Robert D. Burk, A. B. Johnson, N. B. Atkin

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Inactivation of the protein product of the wild-type tumour suppressor gene p53 through complexing of the protein with the E6 oncoprotein of human papillomaviruses (HPV) in HPV-infected cells is thought to be important in the aetiology of cervical carcinoma. Mutations of p53 have also been reported in HPV-negative carcinomas, and we now demonstrate loss of heterozygosity (LOH) of chromosome region 17p13 (in which p53 is located) in such tumours. Immunocytochemical staining with monoclonal antimutant-p53 antibody revealed that the carcinomas with LOH on 17p and completely lacking H PV DNA sequences had mutant p53. Thus the LOH had apparently resulted in the loss of the wild-type allele. Consequently, in both HPV-positive and HPV-negative tumours there is loss of function of wild-type p53, in the former because the protein product of the p53 gene complexes with that of the viral E6 gene, in the latter because the protein is altered, presumably as a result of a direct alteration of the p53 gene but possibly because of other post-translational changes. That this mutant allele of the tumour suppressor gene may sometimes behave like an oncogene is suggested by the presence of more than the expected number of copies of the remaining chromosome 17 homologue in some carcinomas.

Original languageEnglish (US)
Pages (from-to)140-142
Number of pages3
JournalThe Lancet
Volume340
Issue number8812
DOIs
StatePublished - Jul 18 1992

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Loss of Heterozygosity
Chromosomes
Carcinoma
p53 Genes
Tumor Suppressor Genes
Proteins
Alleles
Chromosomes, Human, Pair 17
Viral Genes
Oncogene Proteins
Oncogenes
Neoplasms
Staining and Labeling
Mutation
Antibodies

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Loss of heterozygosity on chromosome 17p and mutant p53 in HPV-negative cervical carcinomas. / Kaelbling, M.; Klinger, HaroldP; Burk, Robert D.; Johnson, A. B.; Atkin, N. B.

In: The Lancet, Vol. 340, No. 8812, 18.07.1992, p. 140-142.

Research output: Contribution to journalArticle

Kaelbling, M. ; Klinger, HaroldP ; Burk, Robert D. ; Johnson, A. B. ; Atkin, N. B. / Loss of heterozygosity on chromosome 17p and mutant p53 in HPV-negative cervical carcinomas. In: The Lancet. 1992 ; Vol. 340, No. 8812. pp. 140-142.
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