Analysis of BAP1 Germline Gene Mutation in Young Uveal Melanoma Patients. (June 2015)

• Record Type: Journal Article
• Authors: Cebulla, Colleen M.; Binkley, Elaine M.; Pilarski, Robert; Massengill, James B.; Rai, Karan; Liebner, David A.; Marino, Meghan J.; Singh, Arun D.; Abdel-Rahman, Mohamed H.
• Is Part Of: Ophthalmic genetics. Volume 36:Number 2(2015:Jun.)
• Page Start: 126
• Page End: 131
• Publication Date: 2015-06
• Subjects: Eye -- Diseases -- Genetic aspects -- Periodicals; Eye Diseases -- genetics -- Periodicals; Eye Diseases -- in infancy & childhood -- Periodicals; 617.7
• DOI: 10.3109/13816810.2015.1010734
• Languages: English
• ISSNs: 1381-6810

Abstract

<abstract> <title>Abstract</title> <p> <italic>Background</italic>: To evaluate the prevalence of <italic>BAP1</italic> germline mutations in a series of young patients with uveal melanoma (UM), diagnosed before age 30.</p> <p> <italic>Materials and Methods</italic>: The study was carried out on 14 young uveal melanoma patients (average age 21.4 years, range 3 months to 29 years). Germline DNA was extracted from peripheral blood. <italic>BAP1</italic> sequencing was carried out using direct sequencing of all exons and adjacent intronic sequences. We also tested for germline mutations in additional melanoma-associated candidate genes <italic>CDKN2A</italic> and <italic>CDK4</italic> (exon 4).</p> <p> <italic>Results</italic>: We identified one patient with a pathogenic mutation (c. 1717delC, p.L573fs*3) in <italic>BAP1</italic>. This patient was diagnosed with UM at age 18 years and had a family history of a father with UM and a paternal grandfather with cancer of unknown origin. One additional patient had an intronic variant of uncertain significance (c.123-48T > G) in <italic>BAP1</italic> while the remaining 12 patients had no alteration. None of the patients had <italic>CDKN2A</italic> or <italic>CDK4</italic> (Exon 4) mutations. Family history was positive for a number of additional malignancies in this series, in particular for cutaneous melanoma, prostate, breast and colon cancers. There were no families with a history of mesothelioma or renal cell carcinoma.</p> <p> <italic>Conclusions</italic>: This study suggests that a small subset of patients with early onset UM has germline mutation in <italic>BAP1.</italic> While young patients with UM should be screened for germline <italic>BAP1</italic> mutations, our results suggest that there is a need to identify other candidate genes which are responsible for UM in young patients.</p> </abstract>