title: BAP1 Germline Mutations in Finnish Patients with Uveal Melanoma.
abstract: 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.
  
  
  
  Cohort study.
  
  
  
  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.
  
  
  
  Sequencing BAP1.
  
  
  
  Pathogenic variants in BAP1.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Folkhälsan Institute of Genetics, Helsinki, Finland. Electronic address: joni.turunen@helsinki.fi.
authors.forename: Joni A
authors.initials: JA
authors.lastname: Turunen
authors.affiliation: Folkhälsan Institute of Genetics, Helsinki, Finland.
authors.forename: Salla
authors.initials: S
authors.lastname: Markkinen
authors.affiliation: Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Rosi
authors.initials: R
authors.lastname: Wilska
authors.affiliation: Department of Medical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Silva
authors.initials: S
authors.lastname: Saarinen
authors.affiliation: Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Virpi
authors.initials: V
authors.lastname: Raivio
authors.affiliation: Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Martin
authors.initials: M
authors.lastname: Täll
authors.affiliation: Folkhälsan Institute of Genetics, Helsinki, Finland; Neuroscience Center and Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland.
authors.forename: Anna-Elina
authors.initials: AE
authors.lastname: Lehesjoki
authors.affiliation: Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Tero T
authors.initials: TT
authors.lastname: Kivelä
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005091:Exons / Q000235:genetics; D005260:Female; D005387:Finland; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D010375:Pedigree; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D043222:Ubiquitin Thiolesterase / Q000235:genetics*; D014604:Uveal Neoplasms / Q000235:genetics*; D055815:Young Adult; D000098943:Uveal Melanoma
chemical_list: C400134:BAP1 protein, human; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase