Concurrent germline and somatic pathogenic BAP1 variants in a patient with metastatic bladder cancer.

Germline pathogenic variants in the BRCA1-associated protein-1 (BAP1) gene cause the BAP1 tumor predisposition syndrome (TPDS). BAP1 TPDS is associated with an increased risk of uveal and cutaneous melanoma, mesothelioma, renal cell carcinoma, and several other cancer subtypes. Here, we report a germline nonsense BAP1 variant (c.850G>T, p.Glu284Ter) in a patient with bladder cancer and a strong family history of malignancy. Concurrently, we identified a somatic frameshift BAP1 variant, and as expected, immunostaining validated the loss of BAP1 protein in patient-derived tumor specimens. Together, these data provide strong evidence of pathogenicity in this case. With the addition of bladder cancer to the tumor types reported with germline BAP1 mutations, our understanding of the BAP1 TPDS continues to evolve, and may affect future screening and surveillance guidelines.

NPJ genomic medicine. 2020 Mar 23*** epublish ***

Megan E Tesch, Justin A Pater, Gillian Vandekerkhove, Gang Wang, Kristin Binnington, Alan I So, Alexander W Wyatt, Bernhard J Eigl

1Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, BC Canada., 2Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA USA., 3Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC Canada., 4Department of Pathology, British Columbia Cancer Agency, Vancouver, BC Canada., 5Hereditary Cancer Program, British Columbia Cancer Agency, Vancouver, BC Canada.