Analysis of BAP1 Germline Gene Mutation in Young Uveal Melanoma Patients

Colleen M Cebulla; Elaine M Binkley; Robert Pilarski; James B Massengill; Karan Rai; David A Liebner; Meghan J Marino; Arun D Singh; Mohamed H Abdel-Rahman

doi:10.3109/13816810.2015.1010734

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Analysis of BAP1 Germline Gene Mutation in Young Uveal Melanoma Patients

Journal article

Peer reviewed

Analysis of BAP1 Germline Gene Mutation in Young Uveal Melanoma Patients

Colleen M Cebulla, Elaine M Binkley, Robert Pilarski, James B Massengill, Karan Rai, David A Liebner, Meghan J Marino, Arun D Singh and Mohamed H Abdel-Rahman

Ophthalmic genetics, Vol.36(2), pp.126-131

04/03/2015

DOI: 10.3109/13816810.2015.1010734

PMCID: PMC4540182

PMID: 25687217

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Abstract

Background: To evaluate the prevalence of BAP1 germline mutations in a series of young patients with uveal melanoma (UM), diagnosed before age 30. Materials and Methods: 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. BAP1 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 CDKN2A and CDK4 (exon 4). Results: We identified one patient with a pathogenic mutation (c. 1717delC, p.L573fs*3) in BAP1. 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 BAP1 while the remaining 12 patients had no alteration. None of the patients had CDKN2A or CDK4 (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. Conclusions: This study suggests that a small subset of patients with early onset UM has germline mutation in BAP1. While young patients with UM should be screened for germline BAP1 mutations, our results suggest that there is a need to identify other candidate genes which are responsible for UM in young patients.

familial cancer

uveal melanoma

BAP1

Details

Title: Subtitle: Analysis of BAP1 Germline Gene Mutation in Young Uveal Melanoma Patients
Creators: Colleen M Cebulla - Havener Eye Institute, Department of Ophthalmology and Visual Science
Elaine M Binkley - Havener Eye Institute, Department of Ophthalmology and Visual Science
Robert Pilarski - Department of Internal Medicine, Division of Human Genetics
James B Massengill - Havener Eye Institute, Department of Ophthalmology and Visual Science
Karan Rai - Department of Internal Medicine, Division of Human Genetics
David A Liebner - Department of Biomedical Informatics, The Ohio State University Wexner Medical Center
Meghan J Marino - The Cole Eye Institute, The Cleveland Clinic
Arun D Singh - The Cole Eye Institute, The Cleveland Clinic
Mohamed H Abdel-Rahman - Department of Pathology, Menoufiya University
Resource Type: Journal article
Publication Details: Ophthalmic genetics, Vol.36(2), pp.126-131
DOI: 10.3109/13816810.2015.1010734
PMID: 25687217
PMCID: PMC4540182
NLM abbreviation: Ophthalmic Genet
ISSN: 1381-6810
eISSN: 1744-5094
Publisher: Informa Healthcare
Language: English
Date published: 04/03/2015
Academic Unit: Ophthalmology and Visual Sciences
Record Identifier: 9984102316302771

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