Etude in silico des mutations du gène BRCA1 identifiées chez des patients cancéreux Algériens

Abstract

The BRCAI gene is a tumor suppressor gene and its molecular alteration may lead to an increased risk of breast and ovarian cancer. In order to contribute to the molecular study, we were interested in the in silico study of the functionalities of two mutations of the BRCAI gene identified in Algerian patients, namely, c.122A>G mutation and c135G>C mutation. Thus, the deleterious effects of two mutations were predicted using an in silico study protocol consisting of different software (I-Mutant 2.0; SIFT: Polyphen-2; AlignGVGD; Project HOPE). The c.122AG mutation is predicted to be deleterious altering the BRCA1 protein while the c.135G>C substitution is predicted to be non-deleterious. Indeed, physicochemical changes between native and mutated amino acids disrupt the stability of the protein and can cause the loss of interaction with other molecules. Our results have shown that these different software are consistent and that their combination could increase the performance of predicting the effect of these mutations. This study allowed us to better understand the effect of mutations and revealed the importance of prediction studies by bioinformatics software.