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Open AccessArticle

Families with BAP1-Tumor Predisposition Syndrome in The Netherlands: Path to Identification and a Proposal for Genetic Screening Guidelines

1
Department of Ophthalmology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
2
Department of Dermatology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
3
Department of Clinical Genetics, Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands
4
Department of Ophthalmology, Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands
5
Department of Clinical Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
6
Department of Clinical Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
7
Department of Genetics, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
8
Department of Clinical Genetics, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
9
Department of Clinical Genetics, Amsterdam University Medical Centers, 1081 HV Amsterdam, The Netherlands
10
Department of Clinical Genetics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(8), 1114; https://doi.org/10.3390/cancers11081114
Received: 30 June 2019 / Revised: 26 July 2019 / Accepted: 1 August 2019 / Published: 4 August 2019
(This article belongs to the Special Issue Uveal Melanoma)
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Abstract

Germline pathogenic variants in the BRCA1-associated protein-1 (BAP1) gene cause the BAP1-tumor predisposition syndrome (BAP1-TPDS, OMIM 614327). BAP1-TPDS is associated with an increased risk of developing uveal melanoma (UM), cutaneous melanoma (CM), malignant mesothelioma (MMe), renal cell carcinoma (RCC), meningioma, cholangiocarcinoma, multiple non-melanoma skin cancers, and BAP1-inactivated nevi. Because of this increased risk, it is important to identify patients with BAP1-TPDS. The associated tumors are treated by different medical disciplines, emphasizing the need for generally applicable guidelines for initiating genetic analysis. In this study, we describe the path to identification of BAP1-TPDS in 21 probands found in the Netherlands and the family history at the time of presentation. We report two cases of de novo BAP1 germline mutations (2/21, 9.5%). Findings of this study combined with previously published literature, led to a proposal of guidelines for genetic referral. We recommend genetic analysis in patients with ≥2 BAP1-TPDS-associated tumors in their medical history and/or family history. We also propose to test germline BAP1 in patients diagnosed with UM <40 years, CM <18 years, MMe <50 years, or RCC <46 years. Furthermore, other candidate susceptibility genes for tumor types associated with BAP1-TPDS are discussed, which can be included in gene panels when testing patients. View Full-Text
Keywords: BAP1; BAP1 tumor predisposition syndrome; germline; referral guidelines BAP1; BAP1 tumor predisposition syndrome; germline; referral guidelines
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Chau, C.; van Doorn, R.; van Poppelen, N.M.; van der Stoep, N.; Mensenkamp, A.R.; Sijmons, R.H.; van Paassen, B.W.; van den Ouweland, A.M.W.; Naus, N.C.; van der Hout, A.H.; Potjer, T.P.; Bleeker, F.E.; Wevers, M.R.; van Hest, L.P.; Jongmans, M.C.J.; Marinkovic, M.; Bleeker, J.C.; Jager, M.J.; Luyten, G.P.M.; Nielsen, M. Families with BAP1-Tumor Predisposition Syndrome in The Netherlands: Path to Identification and a Proposal for Genetic Screening Guidelines. Cancers 2019, 11, 1114.

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