Germ Line BAP1 Mutation in Patients with Uveal Melanoma and Renal Cell Carcinoma

Abstract

Uveal melanoma (UM) and renal cell carcinoma (RCC) can occur sporadically and as a manifestation of <i>BAP1</i> tumor predisposition syndrome. We aimed to understand the prevalence of germ line <i>BAP1</i> pathogenic variants in patients with UM and RCC. We reviewed patients managed at Cleveland Clinic between November 2003 and November 2019 who were diagnosed with UM and RCC. Charts were reviewed for demographic and cancer-related characteristics. RCC samples were tested for <i>BAP1</i> protein expression using immunohistochemical (IHC) staining, and testing for germ line <i>BAP1</i> pathogenic variants was performed as part of routine clinical care. Thirteen patients were included in the study. The average age at diagnosis of UM was 61.3 years. Seven patients underwent fine-needle aspiration biopsy for prognostic testing of UM (low risk =5, high risk =2). Twelve patients were treated with plaque radiation therapy, and 3 patients developed metastatic disease requiring systemic therapy. The median time to diagnosis of RCC from time of diagnosis of UM was 0 months. RCC samples were available for 7 patients for BAP1 IHC staining (intact =6, loss =1). All patients underwent nephrectomy (total = 3, partial = 8, unknown =2), and 1 received systemic therapy for metastatic RCC. Six patients underwent germ line <i>BAP1</i> genetic testing. Of these, 1 patient was heterozygous for a pathogenic variant of <i>BAP1</i> gene: c.1781-1782delGG, p.Gly594Valfs*48. The overall prevalence of germ line <i>BAP1</i> pathogenic variants in our study was high (1/6; 17%; 95% CI 0–46%). Patients with UM and RCC should be referred for genetic counseling to discuss genetic testing.