PD. Sarr, S. Touré, E. El Fahime, JPD. Diop, SA. Ba, Y. Dia, B. Mbengue, M. Sylla Niang, A. Dièye, R. Ndiaye Diallo.
DOI: 10.54266/ajo.2.1s.c1.THNkljUT2E
ABSTRACT
INTRODUCTION: Looking for the mutational landscape on a genomic scale has provided in the last few years unprecedented perspectives for understanding molecular pathogenesis of cancer progression, response to treatment and genetic predisposition. In oral cancers, numerous genomic studies have been devoted to alterations in the TP53 gene and their clinical significance in carcinogenesis. Herein, we screened for genomic variants of TP53 predisposing to oral cancers in Senegalese patients. MATERIALS AND METHODS: Eighty-eight patients with confirmed diagnostic were recruited after informed consent from Stomatology Unit of Aristide le Dantec Hospital. Blood samples were collected from each patient to perform DNA extraction, PCR amplification of all coding exons of TP53 followed by Sanger Sequencing of PCR products. Nucleotidic sequences were analyzed with Genalys software. RESULTS: Mean age at diagnosis was estimated at 51.9 ± 17.98 years with a sex-ratio of 0.76. The majority of patients (64/88) had a negative alcohol-tobacco status. Tumor histology showed that 90% of patients had squamous cell carcinoma localised preferentially on the tongue (22.7%), gum (20.5%) and cheek mucosa (19.3%). Mutation screening of TP53 showed that 52.27% of the patients carried at least one mutation. Eleven genomic variants were identified, seven already reported in mutation databases and four new variants. The most recurrent variants was p.Pro72Arg (rs1042522; Arginine allelic frequency estimated at 31.26%) and a 16 bp deletion in intron 3 (rs59758982; allelic frequency estimated at 26.25%). Linkage disequilibrium (LD) calculation has shown that these two variants are in strong LD but tests of association with controls show that they could not predispose towards oral cancers. CONCLUSION: The results of the present investigation suggest that the two most common variants found in Senegalese patients are not predisposing to oral cancers. Further comprehensive investigations on reported and new variants found in this study should be conducted to highlight their functional impacts and hypothetic oncogenic associated function.