TP53 MUTATIONS IN THE TRANSITION OF PLEOMORPHIC ADENOMA TO CARCINOMA EX PLEOMORPHIC ADENOMA

Abstract

<h3>Objectives</h3> Carcinoma ex pleomorphic adenoma (CXPA) development is considered a sequential process, with genetic mutations determining phenotypic tumor progression. In this sense, the transition from a pleomorphic adenoma (PA) to CXPA can be attributed to the acquisition of mutational events in tumor suppressor genes such as TP53. This study aims to investigate the TP53 mutations at different stages of progression, based on whole-exome sequencing (WES). <h3>Study Design</h3> WES was successfully performed on DNA samples from 10 individuals with CXPA, 7 with PA, and 4 with residual PA. Sequencing reads were aligned to the hg38 reference genome. Single nucleotide polymorphisms were identified for all samples. Quality and variant frequency filters were applied to the data. <h3>Results</h3> No genetic alterations in TP53 were found in individuals with PA. In residual PA, 1 variant classed as moderate impact (missense) was found. In CXPA, we found 1 variant of moderate impact (missense) and the other of high impact (stop gained). <h3>Conclusions</h3> Our findings emphasize that CXPA has genetic alterations of TP53, unlike PA. However, residual PA shared these alterations. The results suggest that TP53 mutations are already present in the premalignant tissues at the beginning of CXPA carcinogenesis.