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.

BRCA1相关蛋白1（BAP1）基因中的种系致病变异导致BAP1肿瘤易感综合征（TPDS）。BAP1 TPDS与葡萄膜和皮肤黑色素瘤，间皮瘤，肾细胞癌和其他几种癌症亚型的风险增加有关。在这里，我们报告了患有膀胱癌和恶性家族病史的患者的生殖细胞无意义BAP1变体（c.850G> T，p.Glu284Ter）。同时，我们确定了体细胞移码BAP1变体，并且正如预期的那样，免疫染色验证了患者来源的肿瘤标本中BAP1蛋白的丢失。这些数据在一起提供了在这种情况下致病性的有力证据。随着种系BAP1报道的肿瘤类型增加了膀胱癌 突变，我们对BAP1 TPDS的理解仍在不断发展，并可能影响未来的筛查和监测指南。