Penetrance of the p53 Gene in Uterine Fibroids in Senegalese Women

Uterine Leiomyoma are a very common benign tumors, affecting 20-30% of the female population over 35 years of age. Black women are the most affected compared to Caucasian women. In order to determine the genetic mecanisms involved in uterine fibroids in senegalese women, the study of penetrance of mutations of exon 4 of the gene was carried out. Our study is based on 27 patients with uterine fibroids. Samples of tumour tissue and blood were taken from each patient. After PCR-Sequencing, identification of mutations was carried out using Mutation Surveyor 5.0.1 and AlamutVisual 2.12 software. Pathogenicity mutations was evaluated with Polyphen-2, Mutation Taster and SIFT. After cleaning, correcting and aligning of sequences with BioEdit software, nucleotide variability, diversity, genetic evolution, correlation of tumors with epidemiological factors and tumors prevalence were determined with Dnasp 5.10.01, MEGA 7.0.14, Arlequin 3.5.3.1 and Rstudio 3.5.1 statistical software. Our results showed a high rate of polymorphism in tumour tissues (19 mutations) compared to blood samples (1 single mutation) but also a genetic difference between tumour and blood tissues. Mutations c.164C>A and c.215C>G affecting respectively codon 55 and 72 of p53 gene were significantly present in uterine fibroids tissues compared to blood. A first time mutation at position c.326T>C located in a specific DNA binding domain (a highly conserved area) and having pathological effects was found in uterine myomas. They also showed a structuring of the leiomyomas according to the age of the patient (30-40 years are the most affected). In conclusion, this is a fist study in Senegal associating the polymorphism of the p53 gene and the occurrence of uterine fibroids showing that some of variants found in tumour tissues could constitute a susceptibility factor in Senegalese women.