Germline and somatic mutational variants of Tunisian high grade serous ovarian cancer identified by next-generation sequencing.

Background: Ovarian cancer (OC) is one of the leading causes of death from gynecological cancers in the world, primarily due to late stage diagnosis. Genetic mutations in genes involved in key cellular functions such as BRCA1, and BRCA2 significantly contribute to ovarian tumorigenesis. This study investigates the genetic landscape of Tunisian patients with familial or sporadic high-grade serous ovarian carcinoma (HGSOC) to guide therapeutic strategies and genetic counseling.

Methods: We conducted a genetic study by targeted Next-Generation Sequencing (NGS) on 54 Tunisian HGSOC patients. A cancer panel including 31 cancer-associated genes was used to analyze DNA extracted from both paraffin-embedded (FFPE) tumor tissues and blood samples.

Results: Germline and somatic pathogenic variants (PVs) were detected in 20.3% and 27.77% of patients respectively. Five patients carried both germline and somatic BRCA1 PVs. Somatic PVs were identified in Homologous Recombination-related genes including ATM, RAD50, and BRIP1. Interestingly, four recurrent BRCA1 PVs were observed, one of them is novel. Germline BRCA1/2 PVs were significantly more frequent in patients under 50 years of age and were associated with improved overall survival. Additionally, 19 variants of uncertain significance (VUS) were detected.

Conclusion: This study provides the first comprehensive genetic profiling of Tunisian HGSOC patients, highlighting the prevalence of pathogenic mutations in key cancer-related genes. These findings emphasize the importance of genetic screening in the management and treatment of OC particularly in populations with unique genetic backgrounds.