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Coincident inactivation of 14-3-3σ and p16INK4a is an early event in vulval squamous neoplasia

Oncogene volume 21, pages 1876–1881 (2002)Cite this article

Abstract

The structure and expression of 14-3-3 σ(σ) was analysed in squamous carcinomas (SCC) of the vulva and in the vulval pre-malignant lesion vulval intraepithelial neoplasia (VIN). Sequence analysis of the σ coding region did not detect mutations in any case of SCC or VIN III and loss of heterozygosity (LOH) occurred in only 2 out of 27 informative cases. In contrast to the absence of genetic change, methylation-specific PCR (MSP) analysis revealed dense CpG methylation within the σ gene in approximately 60% of cases of vulval SCC, but methylation was not detected in matched, normal epithelial tissue. Methylation was associated in all cases with reduced or absent expression of σ mRNA. There was no correlation between σ methylation and HPV or p53 status. Analysis of pre-malignant vulval intraepithelial neoplasia (VIN) revealed that σ methylation was detectable early in neoplastic development. Co-incident methylation, accompanied by loss of expression, of σ and p16INK4a was commonly detected in both SCC and VIN III, suggesting that epigenetic silencing of these two genes is an early and important event in vulval neoplasia.

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Acknowledgements

Research in the laboratory of B Gusterson is supported by Breakthrough Breast Cancer.

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Authors and Affiliations

  1. UO Oncologia Medica, Azienda Ospedaliera S Croce e Carle, Via Coppino 26, 12100 Cuneo, Italy

    Milena Gasco

  2. Ludwig Institute For Cancer Research, Imperial College Faculty of Medicine, St Mary's Campus, Norfolk Place, London, W2 1PG, UK

    Alex Sullivan, Claire Repellin, Louise Brooks, Paul J Farrell & Tim Crook

  3. Department of Gynaecological Oncology, University of Sheffield, Northern General Hospital, Sheffield S5 7AU, UK

    John A Tidy

  4. Department of Pathology, University of Glasgow, Western Infirmary, Glasgow, UK

    Barbara Dunne & Barry Gusterson

  5. Department of Histopathology, Imperial College Faculty of Medicine, St Mary's Campus, Norfolk Place, London, W2 1PG, UK

    David J Evans

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  1. Milena Gasco
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  2. Alex Sullivan
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  3. Claire Repellin
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Correspondence to Tim Crook.

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Gasco, M., Sullivan, A., Repellin, C. et al. Coincident inactivation of 14-3-3σ and p16INK4a is an early event in vulval squamous neoplasia. Oncogene 21, 1876–1881 (2002). https://doi.org/10.1038/sj.onc.1205256

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