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Peer-reviewedCC BY-NC-NDNPJ precision oncology

Ovarian sex cord-stromal tumors are part of the BAP1-tumor predisposition syndrome: evidence from human carriers and mouse models.

  • Abdelrahman M Elsayed1
  • Yuwaraj Kadariya2
  • Lindsey Byrne3
  • Eleonora Sementino2
  • Leigha Senter3
  • Isabella Gray1
  • Olivia Taylor
  • Asmaa Mosbeh1
  • Naomi Canny2
  • Ying L Liu4
  • Christa I Nagel5
  • Joseph McElroy6
5 more authors
  • Rania Sheikh7
  • Colleen M Cebulla1
  • Maria I Carlo8
  • Mohamed H Abdel-Rahman9,10
  • Joseph R Testa11
11 affiliations
  1. 1Havener Eye Institute, Department of Ophthalmology and Visual Sciences, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
  2. 2Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
  3. 3Division of Human Genetics, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
  4. 4Department of Gynecological Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  5. 5Division of Gynecologic Oncology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
  6. 6Center for Biostatistics, Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH, USA.
  7. 7Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  8. 8Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  9. 9Havener Eye Institute, Department of Ophthalmology and Visual Sciences, The Ohio State University Wexner Medical Center, Columbus, OH, USA. [email protected].
  10. 10Division of Human Genetics, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA. [email protected].
  11. 11Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA, USA. [email protected].
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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.

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Cite

BibTeXRIS
BibTeX
@article{elsayed2026ovarian,
  title = {{Ovarian sex cord-stromal tumors are part of the BAP1-tumor predisposition syndrome: evidence from human carriers and mouse models.}},
  author = {Abdelrahman M Elsayed and Yuwaraj Kadariya and Lindsey Byrne and Eleonora Sementino and Leigha Senter and Isabella Gray and Olivia Taylor and Asmaa Mosbeh and Naomi Canny and Ying L Liu and Christa I Nagel and Joseph McElroy and Rania Sheikh and Colleen M Cebulla and Maria I Carlo and Mohamed H Abdel-Rahman and Joseph R Testa},
  journal = {NPJ precision oncology},
  year = {2026},
  month = oct,
  doi = {10.1038/s41698-026-01741-2},
  url = {https://europepmc.org/article/MED/42957746},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Ovarian sex cord-stromal tumors are part of the BAP1-tumor predisposition syndrome: evidence from human carriers and mouse models.
AU  - Abdelrahman M Elsayed
AU  - Yuwaraj Kadariya
AU  - Lindsey Byrne
AU  - Eleonora Sementino
AU  - Leigha Senter
AU  - Isabella Gray
AU  - Olivia Taylor
AU  - Asmaa Mosbeh
AU  - Naomi Canny
AU  - Ying L Liu
AU  - Christa I Nagel
AU  - Joseph McElroy
AU  - Rania Sheikh
AU  - Colleen M Cebulla
AU  - Maria I Carlo
AU  - Mohamed H Abdel-Rahman
AU  - Joseph R Testa
PY  - 2026
DA  - 2026/10/21
JO  - NPJ precision oncology
DO  - 10.1038/s41698-026-01741-2
UR  - https://europepmc.org/article/MED/42957746
AB  - 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.
SN  - 2397-768X
ER  -