BAP1 germline mutations in uveal melanoma patients without family history of eye cancer

Abstract

PurposeGermline pathogenic variants of the BRCA‐1 associated protein‐1 (BAP1) gene predispose to uveal melanoma and several other cancers. Testing for germline BAP1 mutations should be performed if typical BAP1 cancer predisposition syndrome tumors have been diagnosed in the family. We report the frequency of germline pathogenic variants of BAP1 in consecutive Finnish uveal melanoma patients without known history of eye cancer.MethodsIn Finland, uveal melanomas are treated centrally in the Ocular Oncology Service, Helsinki University Hospital. We collected clinical data and genomic DNA from 239 of 389 consecutive patients diagnosed from January 2010 to December 2015. Patients with verified family history of eye cancer were excluded. Fifteen patients had died before the study started and could not be sampled. The exons and exon‐intron junctions of BAP1 were sequenced.ResultsWe found only one probable pathogenic germline variant, a donor splice site mutation in a highly conserved region immediately after exon 2 in a 57‐year‐old male patient. Three of his family members had been diagnosed with typical BAP1‐related cancers (cutaneous melanoma, mesothelioma, and renal cell carcinoma). The mutation was not found in 61,486 controls from the ExAC (http://exac.broadinstitute.org). The frequency of germline BAP1 mutation in patients without any family history of eye cancer was 0.4% (1/239, 95% CI 0.01 to 2.2).ConclusionsThe frequency of BAP1 germline pathogenic variants in the Finnish patients with uveal melanoma without family history of ocular cancer is low. The family history of typical BAP1‐related cancers was informative, and should routinely be obtained to guide the BAP1 genetic testing.