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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Research in the laboratory of B Gusterson is supported by Breakthrough Breast Cancer.
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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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DOI: https://doi.org/10.1038/sj.onc.1205256
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