title: BRCA2 mutations in a population-based series of patients with ocular melanoma.
abstract: We studied the BRCA2 gene for germline mutations in 71 of 99 patients (72%) with ocular melanoma who were diagnosed consecutively in Australia in 1997 and 1998. Patients considered for our study fulfilled one of the following critiera: (i) were 50 years of age or less at diagnosis; (ii) had bilateral disease (2 patients); (iii) reported a family history of ocular melanoma (4 patients). Mutation detection was performed using the protein truncation test and denaturing high-performance liquid chromatography with primers designed to include intron-exon boundaries. Six DNA changes were found of which 2 were exonic, in exons 14 (A>C in nucleotide 7244 leading to His>Arg) and 27 (base pair substitution in nucleotide 9976 leading to a stop codon). One exonic change has been reported previously. None of the intronic mutations were deemed to affect splicing efficiency. Neither exonic mutation was in a person with bilateral ocular melanoma or a family history of cutaneous melanoma. We estimated the prevalence of possible loss of function changes in BRCA2 in patients with ocular melanoma at 3% (95% CI 0-10%). This figure was similar to previous estimates of 2.8% and 2% in nonrepresentative samples of patients with ocular melanoma and 2.1% in a representative sample of young women with breast cancer.
authors.affiliation: Discipline of Medical Genetics, Faculty of Health, University of Newcastle, Callaghan, Australia. scott@hunter.health.nsw.gov.au
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
authors.forename: Claire M
authors.initials: CM
authors.lastname: Vajdic
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Armstrong
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ainsworth
authors.forename: Cliff J
authors.initials: CJ
authors.lastname: Meldrum
authors.forename: Joanne F
authors.initials: JF
authors.lastname: Aitken
authors.forename: Anne
authors.initials: A
authors.lastname: Kricker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005091:Exons; D005134:Eye Neoplasms / Q000235:genetics*; D005260:Female; D024522:Genes, BRCA2; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation