title: BRAF as a melanoma susceptibility candidate gene?
abstract: A high frequency of activating BRAF somatic mutations have been identified recently in malignant melanoma and nevi indicating that BRAF activation could be an early and critical step in the initiation of melanocytic neoplasia. To determine whether BRAF mutations could be an earlier event occurring at the germline level, we screened the entire BRAF coding region for germline mutations in 80 independent melanoma-prone families or patients with multiple primary melanoma without a familial history. We identified 13 BRAF variants, 4 of which were silent mutations in coding regions and 9 nucleotide substitutions in introns. None of these BRAF variants segregated with melanoma in the 11 melanoma families studied. Moreover, there was no significant difference in the frequency of heterozygotes for BRAF variants between melanoma cases and controls when they were compared. Our data suggest that BRAF is unlikely to be a melanoma susceptibility gene.
authors.affiliation: Service de Génétique, Institut Gustave Roussy, 94800 Villejuif, Cedex, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Laud
authors.forename: Caroline
authors.initials: C
authors.lastname: Kannengiesser
authors.forename: Marie-Francoise
authors.initials: MF
authors.lastname: Avril
authors.forename: Agnès
authors.initials: A
authors.lastname: Chompret
authors.forename: Dominique
authors.initials: D
authors.lastname: Stoppa-Lyonnet
authors.forename: Laurence
authors.initials: L
authors.lastname: Desjardins
authors.forename: Alain
authors.initials: A
authors.lastname: Eychene
authors.forename: Florence
authors.initials: F
authors.lastname: Demenais
authors.forename: Gilbert M
authors.initials: GM
authors.lastname: Lenoir
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bressac-de Paillerets
mesh_terms: D020090:Chromosome Segregation; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005190:Family; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D007438:Introns / Q000235:genetics; D008545:Melanoma / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D009378:Neoplasms, Multiple Primary / Q000235:genetics; D009380:Neoplasms, Nerve Tissue / Q000235:genetics; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics; D009508:Nevus, Pigmented / Q000235:genetics; D017354:Point Mutation; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000502:physiology*; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf