BRAF as a melanoma susceptibility candidate gene?
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.
Laud
Karine
K
Service de Génétique, Institut Gustave Roussy, 94800 Villejuif, Cedex, France.
Kannengiesser
Caroline
C
Avril
Marie-Francoise
MF
Chompret
Agnès
A
Stoppa-Lyonnet
Dominique
D
Desjardins
Laurence
L
Eychene
Alain
A
Demenais
Florence
F
Lenoir
Gilbert M
GM
Bressac-de Paillerets
Brigitte
B
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*
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf