Coincident inactivation of 14-3-3σ and p16INK4a is an early event in vulval squamous neoplasia
2002; Springer Nature; Volume: 21; Issue: 12 Linguagem: Inglês
10.1038/sj.onc.1205256
ISSN1476-5594
AutoresMilena Gasco, Alex Sullivan, Claire E. Repellin, Louise Brooks, Paul J. Farrell, John Tidy, Barbara Dunne, Barry A. Gusterson, David J. Evans, Tim Crook,
Tópico(s)Ubiquitin and proteasome pathways
ResumoThe 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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