title: CDKN2A mutations in melanoma families from Uruguay.
abstract: BACKGROUND
  Familial melanoma, a cluster of several cases within a single family, accounts for approximately 10% of cases of melanoma. Hereditary melanoma is defined as two or more first-degree relatives having melanoma. A member of a melanoma-prone family has a 35-70-fold increased relative risk of developing a melanoma. Genetic susceptibility is linked to the major susceptibility genes CDKN2A and CDK4, and the minor susceptibility gene MC1R.
  
  
  OBJECTIVE
  To determine the clinical and genetic characteristics of cutaneous melanoma in melanoma-prone families from Uruguay.
  
  
  METHODS
  We studied 13 individuals from six melanoma-prone families living in Uruguay. Phenotype, familial and personal history were recorded. Molecular screening of CDKN2A and CDK4 was done by polymerase chain reaction-single strand conformational polymorphism analysis. The MC1R gene was sequenced.
  
  
  RESULTS
  Mutations in CDKN2A were detected in five of six families: c.-34G>T, p.G101W and p.E88X. A novel germline mutation p.E88X, associated with hereditary melanoma in two unrelated families, is described. We hypothesize that a founder effect occurred probably in the Mediterranean region. No mutations in CDK4 were detected. Six different MC1R variants, all previously reported, were present in Uruguayan families.
  
  
  CONCLUSIONS
  The overall rate of deleterious CDKN2A mutations in our familial melanoma pedigrees, even though the sample size is small, was considerably higher (83%) than the often quoted range.
authors.affiliation: Departamento Básico de Medicina, Cátedra de Dermatología, Unidad de Oncogenética, Hospital de Clínicas, Facultad de Medicina, GenoMEL Latin America, Montevideo, Uruguay.
authors.forename: A
authors.initials: A
authors.lastname: Larre Borges
authors.forename: A L
authors.initials: AL
authors.lastname: Borges
authors.forename: F
authors.initials: F
authors.lastname: Cuéllar
authors.forename: J A
authors.initials: JA
authors.lastname: Puig-Butillé
authors.forename: M
authors.initials: M
authors.lastname: Scarone
authors.forename: L
authors.initials: L
authors.lastname: Delgado
authors.forename: C
authors.initials: C
authors.lastname: Badenas
authors.forename: M
authors.initials: M
authors.lastname: Milà
authors.forename: J
authors.initials: J
authors.lastname: Malvehy
authors.forename: V
authors.initials: V
authors.lastname: Barquet
authors.forename: J
authors.initials: J
authors.lastname: Núñez
authors.forename: M
authors.initials: M
authors.lastname: Laporte
authors.forename: G
authors.initials: G
authors.lastname: Fernández
authors.forename: P
authors.initials: P
authors.lastname: Levrero
authors.forename: M
authors.initials: M
authors.lastname: Martínez-Asuaga
authors.forename: S
authors.initials: S
authors.lastname: Puig
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics; D005190:Family; D005260:Female; D019942:Genes, p16; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D018807:Polymorphism, Single-Stranded Conformational; D012878:Skin Neoplasms / Q000235:genetics*; D014583:Uruguay; D055815:Young Adult
chemical_list: D051358:Cyclin-Dependent Kinase 4