A Novel BRCA1 Pathogenic Variant in Tunisian Patient With High Grade Ovarian Cancer: Favorable Therapeutic Response...

Ovarian cancer is one of the leading causes of death from gynecological cancer worldwide. Genetic mutations in genes involved in key cellular functions such as BRCA1/2 play a central role in tumorigenesis and have major implications for targeted therapeutic strategies, especially the use of poly (ADP-ribose) polymerase (PARP) inhibitors.

Herein, we described a case of a 50-year-old woman diagnosed with severe anemia secondary to heavy menometrorrhagia. Initial gynecological evaluation, including transvaginal ultrasound, was unremarkable, and endometrial biopsy was not indicated. Imaging revealed no ovarian abnormalities; however, exploratory laparotomy identified a peritoneal nodule, leading to further investigation. Targeted NGS was performed on somatic and germline DNA samples and showed a frame shift deletion of 10 bp (c.1256_1265del: p.R419Ter) in the BRCA1 gene. This variant, identified only in tumor tissues, is novel and classified as pathogenic in ClinVar and ACMG databases. Additional somatic alterations were detected in TP53 and MSH6, while germline testing revealed only a variant of uncertain significance in BARD1. After first-line chemotherapy, the patient benefited from olaparib and achieved a progression-free survival of 23 months with good tolerance and no evidence of disease recurrence.

This finding highlights the importance of integrating tumor-based genomic profiling with germline testing to identify actionable mutations and guide precision oncology. The identification of a novel somatic BRCA1 mutation expands the mutational spectrum of HGSOC and underscores the need to include underrepresented populations, such as those from North Africa, in genomic studies.