title: High frequency of BRAFV600E mutation in acquired nevi and small congenital nevi, but low frequency of mutation in medium-sized congenital nevi.
abstract: To investigate whether the frequency of the BRAF(V600E) (V-raf murine sarcoma virus oncogene homolog B1) mutation in melanocytic nevi is associated with sun exposure patterns, we examined 120 acquired melanocytic nevi excised from various anatomic sites, including glabrous skin, as well as 62 congenital nevi. We used a new mutation detection system based on the shifted termination assay, called Mutector, which was able to detect only 5% of heterozygous mutant cells within the samples. We detected the mutation in 105/120 (87.5%) acquired nevi and 43/62 (69.4%) congenital nevi. Notably, we found the mutation in 35/43 (81.4%) acquired nevi excised from glabrous skin and genitalia. These results strongly suggest that UV light is not necessarily required for the acquisition of the BRAF(V600E) mutation, and suggest that non-mutagenic effects of UV light to melanocytes may be more important in the nevogenesis. Additionally, we showed heterogeneous distribution of BRAF-mutated cells within the lesions of small congenital nevi by a combination of laser microdissection and direct sequencing. Finally, we found low frequency of BRAF(V600E) mutation (6/20, 30.0%) in medium-sized congenital nevi. Most of these nevi with wild-type BRAF had neroblastoma ras viral oncogene homolog mutations (9/14, 64.3%), suggesting different pathogenesis of medium-sized congenital nevi from acquired nevi and small congenital nevi.
authors.affiliation: Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Nami
authors.initials: N
authors.lastname: Ichii-Nakato
authors.forename: Minoru
authors.initials: M
authors.lastname: Takata
authors.forename: Shuko
authors.initials: S
authors.lastname: Takayanagi
authors.forename: Shiho
authors.initials: S
authors.lastname: Takashima
authors.forename: Jingrong
authors.initials: J
authors.lastname: Lin
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Murata
authors.forename: Akihide
authors.initials: A
authors.lastname: Fujimoto
authors.forename: Naohito
authors.initials: N
authors.lastname: Hatta
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Saida
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005820:Genetic Testing; D005835:Genitalia; D006801:Humans; D007223:Infant; D008297:Male; D008544:Melanocytes / Q000473:pathology / Q000528:radiation effects; D042282:Microdissection; D009506:Nevus / Q000151:congenital / Q000235:genetics* / Q000473:pathology; D017354:Point Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012867:Skin / Q000473:pathology; D013472:Sunlight / Q000009:adverse effects*
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf