title: BRAF mutations are also associated with neurocutaneous melanocytosis and large/giant congenital melanocytic nevi.
abstract: NRAS and BRAF mutations occur in congenital melanocytic nevi (CMN), but results are contradictory. Sixty-six prospectively collected CMN patients were analyzed for NRAS Q61 mutations using Sanger sequencing. Negative cases were evaluated for BRAF V600E mutation. NRAS Q61 mutations affected 51 patients (77.3%), and BRAF V600E was found in 5 (7.6%). NRAS Q61 mutation affected 29 (80.6%) of 36 giant, 16 (80.0%) of 20 large, and 5 (62.5%) of 8 medium-size CMN; BRAF mutation affected 1 (5%) of 20 large and 4 (11.4%) of 36 giant CMN. Compared to NRAS, BRAF-mutated nevi show scattered/extensive dermal and subcutaneous nodules (100% BRAF+ vs 34.8% NRAS+) (P=0.002). Neurocutaneous melanocytosis (NCM) affected 16 (24.2%) of 66 patients, with NRAS Q61 mutation in 12 (75.0%), and BRAF V600E in 2 (12.5%), P=0.009. Two patients were negative for both mutations (12.5%). In conclusion, although NRAS Q61 mutations predominate, BRAF V600E mutation also affects patients with large/giant CMN (L/GCMN), and with NCM, a novel finding. BRAF V600E is also associated with increased dermal/subcutaneous nodules. These findings open the possibility of BRAF-targeted therapy in some L/GCMN and NCM cases.
authors.affiliation: 1 Department of Pathology, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Cláudia M
authors.initials: CM
authors.lastname: Salgado
authors.forename: Dipanjan
authors.initials: D
authors.lastname: Basu
authors.forename: Marina
authors.initials: M
authors.lastname: Nikiforova
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Bauer
authors.forename: Donald
authors.initials: D
authors.lastname: Johnson
authors.forename: Veronica
authors.initials: V
authors.lastname: Rundell
authors.forename: Lorelei J
authors.initials: LJ
authors.lastname: Grunwaldt
authors.forename: Miguel
authors.initials: M
authors.lastname: Reyes-Múgica
mesh_terms: D000293:Adolescent; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D020558:GTP Phosphohydrolases / Q000378:metabolism; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009154:Mutation; D020752:Neurocutaneous Syndromes; D009508:Nevus, Pigmented / Q000151:congenital* / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012878:Skin Neoplasms / Q000151:congenital / Q000235:genetics / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D008565:Membrane Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human
keywords: BRAF mutation; NRAS mutation; congenital melanocytic nevus; neurocutaneous melanocytosis; pediatric melanocytic proliferation