TY - JOUR
T1 - Families with BAP1-tumor predisposition syndrome in The Netherlands: Path to identification and a proposal for genetic screening guidelines
AU - Chau, Cindy
AU - van Doorn, Remco
AU - van Poppelen, Natasha M.
AU - van der Stoep, Nienke
AU - Mensenkamp, Arjen R.
AU - Sijmons, Rolf H.
AU - van Paassen, Barbara W.
AU - van den Ouweland, Ans M. W.
AU - Naus, Nicole C.
AU - van der Hout, Annemieke H.
AU - Potjer, Thomas P.
AU - Bleeker, Fonnet E.
AU - Wevers, Marijke R.
AU - van Hest, Liselotte P.
AU - Jongmans, Marjolijn C. J.
AU - Marinkovic, Marina
AU - Bleeker, Jaco C.
AU - Jager, Martine J.
AU - Luyten, Gregorius P. M.
AU - Nielsen, Maartje
PY - 2019/8/1
Y1 - 2019/8/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85070739671&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31382694
U2 - https://doi.org/10.3390/cancers11081114
DO - https://doi.org/10.3390/cancers11081114
M3 - Article
C2 - 31382694
SN - 2072-6694
VL - 11
JO - Cancers
JF - Cancers
IS - 8
M1 - 1114
ER -