Epigenetic inactivation of 14-3-3 sigma in oral carcinoma: Association with p16(INK4a) silencing and human papillomavirus negativity

Gasco, M. et al. (2002) Epigenetic inactivation of 14-3-3 sigma in oral carcinoma: Association with p16(INK4a) silencing and human papillomavirus negativity. Cancer Research, 62(7), pp. 2072-2076.

Abstract

In vitro studies have identified 14-3-3sigma 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 14-3-3sigma 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 14-3-3sigma 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 14-3-3sigma was methylated were significantly more likely to lack DNA sequences from human papillomavirus and to have coincident methylation of p16(INK4a) than cases that expressed 14-3-3sigma. 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 sigma and p16(INK4a) in a subset of SCCs of the oral cavity.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Gusterson, Professor Barry
• Authors: Gasco, M., Bell, A., Heath, V., Sullivan, A., Smith, P., Hiller, L., Yulug, I., Numico, G., Merlano, M., Farrell, P., Tavassoli, M., Gusterson, B., and Crook, T.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
• Journal Name: Cancer Research
• ISSN: 0008-5472