BAP1 Germline Mutations in Finnish Patients with Uveal Melanoma
| Autor: | Tero Kivelä, Salla Markkinen, Anna-Elina Lehesjoki, Virpi Raivio, Rosi Wilska, Martin Täll, Joni A. Turunen, Silva Saarinen |
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| Přispěvatelé: | Clinicum, Department of Ophthalmology and Otorhinolaryngology, Silmäklinikka, Department of Medical and Clinical Genetics, Medicum, Neuroscience Center, Research Programs Unit, Anna-Elina Lehesjoki / Principal Investigator, Research Programme for Molecular Neurology |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
Uveal Neoplasms 0301 basic medicine Oncology PREDICTION Uveal Neoplasm VARIANTS Bioinformatics Polymerase Chain Reaction Germline Cohort Studies 0302 clinical medicine Medicine Family history Melanoma Finland Aged 80 and over education.field_of_study BAP1 Exons Middle Aged CANCER Pedigree 3. Good health 030220 oncology & carcinogenesis Female Ubiquitin Thiolesterase Adult medicine.medical_specialty Population 3122 Cancers Polymorphism Single Nucleotide Young Adult 03 medical and health sciences Germline mutation Internal medicine Humans Genetic Predisposition to Disease 3125 Otorhinolaryngology ophthalmology education Germ-Line Mutation Aged business.industry Tumor Suppressor Proteins Cancer Sequence Analysis DNA medicine.disease eye diseases Ophthalmology 030104 developmental biology CHOROIDAL MELANOMAS 3111 Biomedicine business GENOMICS |
| Popis: | Purpose: Germline mutations of the BRCA1-associated protein-1 gene (BAP1) predispose carriers to uveal melanoma. We report the population-based frequency of germline pathogenic variants of BAP1 in Finnish patients with uveal melanoma who live in a high-risk region for this cancer. Design: Cohort study. Participants: In Finland, uveal melanomas are treated centrally in the Ocular Oncology Service, Helsinki University Hospital. We collected clinical data and genomic DNA from 148 of 188 consecutive patients diagnosed from January 2010 through December 2012. Seven of these patients from 6 families had a history of uveal melanoma in 1 relative, and 2 patients from 2 additional families had such a history in 2 relatives. Methods: Sequencing BAP1. Main Outcome Measures: Pathogenic variants in BAP1. Results: We found 2 different pathogenic variants in BAP1 in 3 patients. Two patients had a single nucleotide insertion in exon 14 resulting in a shift of reading frame. Both had a family history of uveal melanoma in at least 1 relative. One patient without a family history of uveal melanoma had a single nucleotide substitution in the conserved splice donor site of intron 2. BAP1 cancer predisposition syndrome-related cancers were present in all 3 families. The overall frequency of BAP1 pathogenic variants was 2.0% (3/148; 95% confidence interval, 0.4-5.8), the frequency among patients 50 years of age or younger was 3.6% (1/28; 95% confidence interval, 0.1-18), and a pathogenic variant was detected in 2 of 8 families with a history of uveal melanoma. Conclusions: The frequency of BAP1 germline pathogenic variants in consecutive Finnish patients with uveal melanoma who come from a high-risk region for the development of this cancer is comparable with reports from other populations. (C) 2016 by the American Academy of Ophthalmology. |
| Databáze: | OpenAIRE |
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