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.

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.