Comprehensive Genomic Profiling Reveals the Mutational Spectrum and Clinical Significance of BRCA1/2 and Other Cancer-Susceptibility Genes in Breast Cancer Patients from Southern Tunisia
TL;DR
This study investigated germline genetic variants in 165 Tunisian breast cancer patients using targeted next-generation sequencing of a multigene cancer panel to identify pathogenic or likely pathogenic variants in BRCA1 and BRCA2 genes and identified P/LPVs in other genes.
Abstract
Simple Summary Breast cancer is one of the most common cancers among women, but its genetic causes remain poorly characterized in North African populations. In this study, we investigated germline genetic variants in 165 Tunisian breast cancer patients using targeted next-generation sequencing of a multigene cancer panel. We identified pathogenic or likely pathogenic variants (P/LPVs) in BRCA1 and BRCA2 genes in 19 patients (11.5%), with several recurrent variants and additional variants not previously reported in our Tunisian cohort. P/LPV carriers were more frequently younger at diagnosis and showed significant associations with family history and several clinical features. We also identified P/LPVs in other genes. In addition, 56 variants of uncertain significance (VUS) were detected, of which 7 were prioritized through computational analyses. Additional functional or segregation evidence should be collected to establish pathogenicity. Our findings expand the available genetic data on breast cancer in Tunisia and highlight the importance of population-specific genomic studies for improving variant interpretation and genetic counseling.