Germline Genetics of Breast Cancer in North Africa: Insights from Whole-Exome Sequencing

Breast cancer (BC) is the most common malignancy among women in North Africa (NA), yet the genomic landscape of hereditary breast cancer (HBC) in this region remains underexplored. Whole-exome sequencing (WES) offers opportunities to detect both known and novel germline variants, providing insights beyond conventional BRCA1/2 testing. To date, the understanding of HBC in North African populations remains incomplete. Targeted gene panels, although widely used, may miss variants unique to underrepresented groups. In contrast, WES enables the identification of rare and population-specific pathogenic variants (PVs) in both established and candidate genes. This review aimed to summarize current evidence on the application of WES and related genomic approaches in HBC across North African countries and to evaluate their potential contribution to precision oncology. A literature search was conducted using PubMed, Scopus, and Google Scholar to identify relevant studies published between 2015 and 2025. Additional relevant articles were identified through manual reference screening. The available evidence demonstrates substantial heterogeneity in the level of genomic research across the region. Egypt, Tunisia, and Morocco have successfully implemented WES and reported both recurrent PVs and novel candidate susceptibility genes, while Algeria and Mauritania have mainly relied on targeted next-generation sequencing approaches. No published WES studies were identified from Libya, where only limited BRCA1 exon sequencing using the Sanger method has been reported. Studies across several regions in NA have identified recurrent variants, with evidence of possible founder effects in some populations, highlighting the value of comprehensive genomic approaches for uncovering HBC risk factors unique to North African populations. In conclusion, WES is a powerful approach to improve HBC genetics in NA and for identifying clinically relevant population-specific variants, particularly in research field. However, its implementation is still limited by financial and expertise-related barriers, and its findings need appropriate validation before translation into routine clinical care. Continued investment in genomic infrastructure, bioinformatics capacity, and regional collaborative research is essential. Such efforts will advance precision oncology and support the development of region-specific genetic testing strategies.