Inactivation of the p14^ARF, p15^INK4B and p16^INK4A genes is a frequent event in human oral squamous cell carcinomas

Abstract 

The p14^ARF, p15^INK4B and p16^INK4A genes were localized to 9p21, where genetic alterations have been reported frequently in various human tumors. We performed a molecular analysis of the mechanism of inactivation in cell lines and 32 oral squamous cell carcinoma (OSCC), using deletion screening, PCR-SSCP, methylation-specific-PCR and cycle sequencing. We detected homozygous deletion of p14^ARF-1Eβ in 9 (26.5%), of p15^INK4B in one (3.1%), and of p16^INK4A in 22 (56.3%) tumor samples. Three mutations were detected in the p16^INK4A genes. We detected aberrant methylation of the p14^ARF genes in 14 (43.8%), of the p15^INK4B gene in 9 (28.1%), and of the p16^INK4A gene in 16 (50.0%) tumor samples. Altogether, 87.5% of the samples harbored at least one of the alterations in the p14^ARF, p15^INK4B, and p16^INK4A genes, indicating that the frequent inactivation of these genes may be an important mechanism during OSCC development.

Keywords:  p14^ARF, p15^INK4B, p16^INK4A, Gene alteration, Oral cancer