Development of renal cell carcinoma in patients with primary uveal melanoma.

e15563 Background: Somatic mutations of BRCA1 associated protein1 (BAP1), a tumor suppressor gene, located on chromosome 3p21.1 is found in 50% of primary uveal melanoma (UM) and has been linked to an aggressive phenotype. It is recently reported that somatic BAP1 mutation is also found in 15% of renal cell carcinomas (RCC). We hypothesize that germ line or somatic mutation of BAP1 may contribute the carcinogenesis of patients (pts) who have both UM and RCC. Methods: Retrospective chart review on patients with primary UM treated at Wills Eye Institute and Thomas Jefferson University between 1997 and 2012 revealed 15 patients with both UM and histologically proven RCC. Clinical information on these patients was analyzed. Tumor tissue and blood specimens were also collected for BAP1 gene mutation analysis. Results: Of the 15 patients, 12 (80%) were males. Median age at diagnosis of UM was 57 years old. Six of these patients developed liver metastasis on follow-up (40%). From 8 patients whose pathology data on RCC were available, 6 of them were clear cell type (75%), one was papillary type-1 and one was multilocular cystic subtype. The diagnosis of RCC proceeded the UM diagnosis in 5 of 15 patients, while the diagnoses were made concurrently in 4 patients. Six patients were diagnosed with UM first. For pts who had genetic testing on UM, chromosome 3 abnormalities are the most common abnormalities found. Peripheral blood specimens were tested for 2 patients and germ-line BAP1 mutation was not discovered. Detailed tumor tissue BAP1 mutation analysis is ongoing. Conclusions: The development of RCC is relative common for UM and the molecular mechanism is being determined. It is male dominant in sex and mostly clear cell type in histology of RCC. Further gene mutation analysis and its association with clinical data will be reported.