GENETIC POLYMORPHISM AND GENE EXPRESSION OF PI3K GENE IN AMELOBLASTOMA

Abstract

Objective Ameloblastoma is a benign and local aggressive odontogenic tumor. Many genes and their respective signalling pathways are involved in the pathogenesis i.e. Patch, SHH, SMO, PI3K, AKT, mTOR etc. PI3K has an important role i.e. cellular quiescence, proliferation, cancer, and longevity in the pathogenesis of Ameloblastoma through PI3K/AKT/mTOR signalling pathway. The study was designed to evaluate the gene expression and gene polymorphism of PI3K gene. The present study was a prospective preliminary study, which was carried out in 20 patients of confirmed ameloblastoma cases. 5 tooth germs were taken as control to compare. Biopsy was taken with patient's consent. Genomic DNA was extracted to assess the polymorphism of PI3K gene gene sequencing method in exon 9 and exon 20 in association with immunohistochemical analysis respectively. Findings Insertion of AA is noticed as the most common variation among 12 samples out of 20 identified at Exon 9 near to the splice site of PIk3CA (g.24751_24752insAA) (chr3:178890652_178890653insAA). However, no variation at Exon 20 was observed. Variant was neither found in ExAC nor 1000G. No differences were noted in the frequency and type of mutations analyzed by sex, age, or histologic features. The gene expression of PIK3CA was significantly higher in tumor epithelial cells. Such genetic polymorphisms are vital because they can be used as biomarkers that indicate for prognosis of tumor and its biological behavior. Conclusion These results suggest that common genetic variations in these pathways may modulate risk and clinical outcomes of ameloblastoma. Further replication and functional studies are needed to confirm these findings. It will be of benefit to the patient, if we target the mutation or aberrant protein products at the appropriate time by intervention of precised therapy.