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Background <p>Pathogenic variants in <i>BRCA1</i> and <i>BRCA2</i> are well known drivers of homologous recombination deficiency in ovarian carcinoma. Somatic <i>BRCA</i> mutations are observed in a minority of ovarian cancers. The co-occurrence of both <i>BRCA1</i> and <i>BRCA2</i> 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 <i>BRCA1</i> and <i>BRCA2</i> pathogenic variants, with negative germline testing.</p> Case presentation <p>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 <i>BRCA1</i> exon20 (c.5309G &gt; T, p.G1770V) and one in <i>BRCA2</i> exon11 (c.3248del, p.N1083Ifs*4). Germline <i>BRCA</i> testing was negative.</p> Conclusion <p>This case illustrates a rare double somatic inactivation of both <i>BRCA1</i> and <i>BRCA2</i> 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 <i>BRCA</i>-associated ovarian carcinomas and support tumor-based <i>BRCA</i> testing.</p>

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

  • 期刊论文

  • 发表日期：

    2026年2月26日

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  • Nihel Ammous-Boukhris,
  • Rania Abdelmaksoud-Dammak,
  • Ameni Feki,
  • Wala Ben kridis,
  • Afef Khanfir,
  • Ali Gargouri,
  • Raja Mokdad-Gargouri

摘要

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.

Conclusion

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.