Unexpected double-hit BRCA1/BRCA2 somatic mutations in a sporadic endometrioid ovarian carcinoma

Background Pathogenic variants in BRCA1 and BRCA2 are well known drivers of homologous recombination deficiency in ovarian carcinoma. Somatic BRCA mutations are observed in a minority of ovarian cancers. The co-occurrence of both BRCA1 and BRCA2 pathogenic somatic mutations in a single tumor is rare, and to our knowledge this has not been described in endometrioid ovarian carcinoma. We describe a case of endometrioid ovarian carcinoma harboring double somatic BRCA1 and BRCA2 pathogenic variants, with negative germline testing. Case presentation A 50-year-old woman underwent right oophorectomy, anterior pelvic exenteration (including uterus, cervix, rectum) plus omentectomy and mesenteric biopsy for a right ovarian mass. Histopathology revealed a well-differentiated endometrioid adenocarcinoma of the right ovary (pT1c1, Nx, Mx). Tumor tissue NGS identified two pathogenic variants: one in BRCA1 exon20 (c.5309G > T, p.G1770V) and one in BRCA2 exon11 (c.3248del, p.N1083Ifs*4). Germline BRCA testing was negative.

This case illustrates a rare double somatic inactivation of both BRCA1 and BRCA2 in an endometrioid ovarian carcinoma. Given the potential therapeutic implications : sensitivity to platinum and PARP-inhibitors, and the rarity of such a double-hit in non-serous histology, reporting such cases may expand the known spectrum of BRCA-associated ovarian carcinomas and support tumor-based BRCA testing. Similar content being viewed by others Data availability Data are available from the corresponding author upon reasonable request.

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The authors would like to sincerely thank Dr Saloua Krichen Makni, the Anatomopathologist, for her valuable contribution to this work. Her expertise and careful evaluation were essential to the accuracy of this report. Funding This research was supported by the grant of Tunisian ministry of higher education and scientific research (Grant: LR19CBS02). Author information Authors and Affiliations Contributions All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by NAB, RAD. AF, WBK, and AK collected patients ‘data. The first draft of the manuscript was written by NAB, AG, and RMG and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Corresponding author Ethics declarations Competing interests The authors declare no competing interests. Ethics approval and consent to participate This study was conducted in accordance with the Declaration of Helsinki. Ethical approval was obtained from The Faculty of Medicine of Sfax, Tunisia (CPP SUD N°177/2024), and written informed consent was obtained from all participants prior to their inclusion in the study. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Ammous-Boukhris, N., Abdelmaksoud-Dammak, R., Feki, A. et al. Unexpected double-hit BRCA1/BRCA2 somatic mutations in a sporadic endometrioid ovarian carcinoma. Mol Biol Rep 53, 430 (2026). https://doi.org/10.1007/s11033-026-11598-0 Received: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s11033-026-11598-0