{
  "abstract": "Germline heterozygous BAP1 pathogenic/likely pathogenic (P/LP) variants are associated with the BAP1-tumor predisposition syndrome (BAP1-TPDS). This study evaluated evidence for an association between ovarian cancers and BAP1-TPDS. We evaluated ovarian cancer incidence in two independent cohorts of female subjects with germline BAP1 P/LP variants. Additionally, we investigated whether the high incidence of spontaneous ovarian sex cord-stromal tumors (OSCSTs) in heterozygous Bap1-mutant FVB/N mice was strain-specific by examining their occurrence in several other Bap1-mutant mouse models with different genetic backgrounds. In the combined human cohort of 176 females with BAP1 P/LP variants, 7 (4%) had ovarian cancer, including 3 with OSCST. Another OSCST occurred in a patient with a germline BAP1 variant with conflicting pathogenesis, for which functional studies supported pathogenicity. OSCSTs were observed in all mouse strains with germline heterozygous Bap1 mutations (incidence: 32%-73%). Biallelic inactivation of BAP1 was observed in 3/3 human and 10/10 murine OSCSTs. OSCSTs from Bap1-mutant mice showed marked decreases in Bmpr1b, Erb, and Foxl2 expression, suggesting disruption of pathways involved in ovarian differentiation and homeostasis. In conclusion, ovarian cancers, particularly OSCSTs, represent a rarer phenotype of the BAP1-TPDS. Downregulation of Bmpr1b, Erb, and Foxl2 may reflect alterations in pathways amenable to therapeutic targeting in OSCSTs.",
  "abstract_shown": true,
  "affiliations": [
    "Havener Eye Institute, Department of Ophthalmology and Visual Sciences, The Ohio State University Wexner Medical Center, Columbus, OH, USA.",
    "Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA, USA.",
    "Division of Human Genetics, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.",
    "Department of Gynecological Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.",
    "Division of Gynecologic Oncology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.",
    "Center for Biostatistics, Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH, USA.",
    "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.",
    "Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.",
    "Havener Eye Institute, Department of Ophthalmology and Visual Sciences, The Ohio State University Wexner Medical Center, Columbus, OH, USA. Mohamed.Abdel-Rahman@osumc.edu.",
    "Division of Human Genetics, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA. Mohamed.Abdel-Rahman@osumc.edu.",
    "Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA, USA. Joseph.Testa@fccc.edu."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Abdelrahman M Elsayed"
    },
    {
      "affs": [
        1
      ],
      "name": "Yuwaraj Kadariya"
    },
    {
      "affs": [
        2
      ],
      "name": "Lindsey Byrne",
      "orcid": "0000-0001-7131-5331"
    },
    {
      "affs": [
        1
      ],
      "name": "Eleonora Sementino"
    },
    {
      "affs": [
        2
      ],
      "name": "Leigha Senter"
    },
    {
      "affs": [
        0
      ],
      "name": "Isabella Gray"
    },
    {
      "name": "Olivia Taylor"
    },
    {
      "affs": [
        0
      ],
      "name": "Asmaa Mosbeh"
    },
    {
      "affs": [
        1
      ],
      "name": "Naomi Canny"
    },
    {
      "affs": [
        3
      ],
      "name": "Ying L Liu"
    },
    {
      "affs": [
        4
      ],
      "name": "Christa I Nagel"
    },
    {
      "affs": [
        5
      ],
      "name": "Joseph McElroy",
      "orcid": "0000-0003-0366-1210"
    },
    {
      "affs": [
        6
      ],
      "name": "Rania Sheikh"
    },
    {
      "affs": [
        0
      ],
      "name": "Colleen M Cebulla"
    },
    {
      "affs": [
        7
      ],
      "name": "Maria I Carlo",
      "orcid": "0000-0002-4786-7408"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Mohamed H Abdel-Rahman"
    },
    {
      "affs": [
        10
      ],
      "name": "Joseph R Testa",
      "orcid": "0000-0003-1301-5175"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d5mj5x3ffwk36.bib",
  "cited_by": 0,
  "doi": "10.1038/s41698-026-01741-2",
  "fulltext_url": "https://europepmc.org/articles/PMC13720126",
  "id": "d5mj5x3ffwk36",
  "issns": [
    "2397-768X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42957746",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1311|BRCA gene mutations in cancer"
    ]
  ],
  "openalex": "W7223156061",
  "pdf_url": "https://europepmc.org/articles/PMC13720126?pdf=render",
  "pmcid": "PMC13720126",
  "pmid": "42957746",
  "published": "2026-10-21",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/d5mj5x3ffwk36.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:21Z",
      "native_id": "MED:42957746",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42957746"
    },
    {
      "first_seen": "2026-11-02T12:23:58Z",
      "native_id": "PMC13720126",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41698-026-01741-2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|BRCA gene mutations in cancer",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Ovarian sex cord-stromal tumors are part of the BAP1-tumor predisposition syndrome: evidence from human carriers and mouse models.",
  "title_text": "Ovarian sex cord-stromal tumors are part of the BAP1-tumor predisposition syndrome: evidence from human carriers and mouse models.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:04Z",
  "url": "https://research.draconitic.com/paper/d5mj5x3ffwk36",
  "venue": "NPJ precision oncology",
  "versions": []
}