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Epigenetic inactivation of 14-3-3 σ in oral carcinoma : association with p16INK4a silencing and human papillomavirus negativity
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Gasco, M., Bell, A. K., Heath, V., Sullivan, A., Smith, P., Hiller, Louise, Yulug, I., Numico, G., Merlano, M., Farrell, P. J., Tavassoli, M., Gusterson, B. and Crook, T. (2002) Epigenetic inactivation of 14-3-3 σ in oral carcinoma : association with p16INK4a silencing and human papillomavirus negativity. Cancer Research, 62 (7). pp. 2072-2076.
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Official URL: http://cancerres.aacrjournals.org/content/62/7/207...
Abstract
In vitro studies have identified 14-3-3σ as a regulator of senescence in human keratinocytes. To assess its contribution to squamous neoplasia, we have analyzed genetic and epigenetic changes in this gene in squamous cell carcinomas (SCCs) and dysplastic lesions of the oral cavity. No mutations were detected in the coding sequence of 14-3-3σ in 20 oral carcinomas, and there was loss of heterozygosity in only 7 of 40 informative cases. In contrast to the absence of genetic change, aberrant methylation within 14-3-3σ was detected in 32 of 92 squamous cell carcinomas and in 3 of 6 oral dysplasias and was associated with reduced or absent expression at both mRNA and protein levels. Methylation was not detected in matched, normal epithelial tissue controls. Carcinomas in which 14-3-3σ was methylated were significantly more likely to lack DNA sequences from human papillomavirus and to have coincident methylation of p16INK4a than cases that expressed 14-3-3σ. Methylation was detected in SCC, both wild-type and mutant for p53, but was more commonly detected in cancers with wild-type p53. These results implicate coincident epigenetic abrogation of function in both σ and p16INK4a in a subset of SCCs of the oral cavity.
| Item Type: | Journal Article | ||||||
|---|---|---|---|---|---|---|---|
| Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) | ||||||
| Divisions: | Faculty of Medicine > Warwick Medical School > Health Sciences > Clinical Trials Unit Faculty of Medicine > Warwick Medical School > Health Sciences Faculty of Medicine > Warwick Medical School |
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| Journal or Publication Title: | Cancer Research | ||||||
| Publisher: | American Association for Cancer Research | ||||||
| ISSN: | 0008-5472 | ||||||
| Official Date: | 30 January 2002 | ||||||
| Dates: |
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| Volume: | 62 | ||||||
| Number: | 7 | ||||||
| Page Range: | pp. 2072-2076 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Access rights to Published version: | Restricted or Subscription Access |
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