Non-serous ovarian cancer in PTEN Hamartoma Tumor Syndrome: additional evidence for increased risk
Increased hereditary cancer risk is one of the hallmarks of PTEN Hamartoma Tumor Syndrome (PHTS) which is caused by a pathogenic germline variant in PTEN. Case reports and some cohort studies have described ovarian cancer (OC) in PHTS patients. Previously, we observed an enrichment of non-serous OC in PHTS compared to sporadic cases (3% vs 1%). However, ovarian cancer is currently not considered a PHTS-related cancer. The aim of this study was to describe five PHTS patients with a pathogenic germline variant in PTEN with non-serous OC. Three of the non-serous OCs were mucinous carcinomas (49, 51 and 52 years) and two were malignant germ cell tumors (8 and 15 years) and all were diagnosed before genetic testing and PHTS diagnosis. In addition to OC, the described patients developed other PHTS-related benign and malignant lesions. We provide further evidence that non-serous ovarian cancer, especially mucinous, endometrioid and malignant germ cell tumors should be further investigated as potential PHTS-related cancers.
Authors
- Michiel Simons (ORCID: https://orcid.org/0000-0003-1039-3488)
- Nicoline Hoogerbrugge (ORCID: https://orcid.org/0000-0003-2393-8141)
- Marjolijn C.J. Jongmans (ORCID: https://orcid.org/0000-0001-6572-4374)
- Arjen R. Mensenkamp (ORCID: https://orcid.org/0000-0003-3805-877X)
- Vera M. Witjes (ORCID: https://orcid.org/0000-0002-0684-3071)
- Janet R. Vos (ORCID: https://orcid.org/0000-0001-8802-7002)
- Yvette van Ierland (ORCID: https://orcid.org/0000-0003-1055-9855)
- Maartje Nielsen (ORCID: https://orcid.org/0000-0002-5351-1870)
- Edward M. Leter
- Anne M. van Altena (ORCID: https://orcid.org/0000-0003-2598-087X)
- Janneke Schuurs-Hoeijmakers (ORCID: https://orcid.org/0000-0002-8900-2226)
- Muriel A. Adank (ORCID: https://orcid.org/0000-0002-2417-203X)
- Jolanda Schieving (ORCID: https://orcid.org/0000-0003-1605-0128)
- Liselotte P. van Hest (ORCID: https://orcid.org/0000-0002-9373-6601)
- Ane J. Schei‐Andersen (ORCID: https://orcid.org/0000-0001-5897-0606)
- M. de Jong (ORCID: https://orcid.org/0000-0001-8059-466X)
Institutions
- Radboud University Nijmegen (NL)
- Radboud University Medical Center (NL)
- Radboud Institute for Molecular Life Sciences (NL)
- ERN GUARD-Heart (NL)
- ERN GENTURIS (NL)
Publication Details
- Journal
- Familial Cancer
- Published
- 2025-03-18
- DOI
- https://doi.org/10.1007/s10689-025-00453-z
- Citations
- 2
- Primary Topic
- PI3K/AKT/mTOR signaling in cancer
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- Amsterdam University Medical Centers
- European Commission
- Universiteit Leiden
- Universiteit van Amsterdam
- Universiteit Maastricht
- Maastricht Universitair Medisch Centrum
- Leids Universitair Medisch Centrum
- Universitair Medisch Centrum Groningen
- Third Health Programme
- HORIZON EUROPE Marie Sklodowska-Curie Actions