title: Population-based prevalence of CDKN2A and CDK4 mutations in patients with multiple primary melanomas.
abstract: The presence of multiple primary cutaneous melanomas (MPM) has been advocated as guidance to identifying melanoma families. Frequencies of CDKN2A mutations in materials of sporadic MPM cases from pigmented lesion clinics vary between 8 and 15%. Patients with MPM have therefore been regarded as good candidates for CDKN2A mutational screening. We describe a population-based study where all persons in Norway diagnosed with MPM between 1953 and 2004 (n = 738 alive per April 2004) were invited to participate. Three-hundred-and-ninety patients (52.8%) responded confidentially. Mutations in CDKN2A were found in 6.9% of the respondents. Eighty-one MPM patients (20.8%) reported that they belonged to melanoma families, and 17 (21.0%) of these harboured a CDKN2A mutation, compared to 3.2% of the nonfamilial cases. The probability of finding a CDKN2A mutation increased when the patients had three or more melanomas, or a young age of onset of first melanoma. We identified five novel CDKN2A variants (Ala57Gly, Pro81Arg, Ala118Val, Leu130Val, and Arg131Pro) and four that previously have been reported in melanoma families (Glu27X, Met53Ile, Arg87Trp, and Ala127Pro). A large deletion (g.13623_23772del10150) encompassing exon 1alpha and the 5' part of exon 2 was detected in six patients with a family history of melanoma. Three patients, belonging to the same family, had the CDK4 Arg24His mutation. The frequency of CDKN2A mutations was lower than previously reported in other studies, an observation which probably is due to the population-based design of our study.
authors.affiliation: Department of Dermatology, Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo, Norway.
authors.forename: Per
authors.initials: P
authors.lastname: Helsing
authors.forename: Dag Andre
authors.initials: DA
authors.lastname: Nymoen
authors.forename: Sarah
authors.initials: S
authors.lastname: Ariansen
authors.forename: Solrun J
authors.initials: SJ
authors.lastname: Steine
authors.forename: Lovise
authors.initials: L
authors.lastname: Maehle
authors.forename: Steinar
authors.initials: S
authors.lastname: Aamdal
authors.forename: Frøydis
authors.initials: F
authors.lastname: Langmark
authors.forename: Mitchell
authors.initials: M
authors.lastname: Loeb
authors.forename: Lars A
authors.initials: LA
authors.lastname: Akslen
authors.forename: Anders
authors.initials: A
authors.lastname: Molven
authors.forename: Per Arne
authors.initials: PA
authors.lastname: Andresen
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D001483:Base Sequence; D003430:Cross-Sectional Studies; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D005260:Female; D019942:Genes, p16; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D015995:Prevalence; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4