Adenomatous polyposis coli gene mutation and decreased wildtype p53 protein expression in oral submucous fibrosis: A preliminary investigation

Objective. The purpose of this study was to identify the adenomatous polypo sis coli (APC) tumor suppressor gene mutation and level of wild-type p53 pr otein expression in patients with oral submucous fibrosis (OSF). Study design. Cells from OSF and control subjects were cultured in Dulbecco modified Eagle medium with 10%, fetal bovine serum at 37 degreesC. Genomic DNA was extracted from cultured cells and used as a template for polymeras e chain reaction amplification of the APC tumor suppressor gene. The presen ce of wild-type p53 protein in cell lysates of Cultured cells was analyzed by Western blot. Data were analyzed by the sign test for nonparametric samp les and by analysis of variance. Results. The results showed that the APC gene of explant cultured cells fro m OSF patients (8/8) had a CGA-to-GGA transition mutation at codon 498 that resulted in an Arg-to-Gly missense mutation (P < .01). All (8/8) normal HG F cultures revealed expression of the wild-type APC protein. Cells cultured from 7 of 8 OSF patients were also found to have a single nucleotide delet ion at nucleotide 1494 that resulted in creating a stop codon (TGA) at codo n 504 (P < .01). This created a premature signal for the endpoint of transl ation and thus resulted in the generation of a truncated protein product th at encodes a polypeptide of 503 amino acid residue. It was found that wild- type p53 protein in human gingival fibroblast cell cultures was significan tly higher than in OSF cells (P < .01). Conclusion. Alterations of the APC and wild-type p53 tumor suppressor genes in OSF may imply a risk for progression to oral cancer.