BRAFMutations are Also Associated with Neurocutaneous Melanocytosis and Large/Giant Congenital Melanocytic Nevi

NRASand BRAFmutations occur in congenital melanocytic nevi (CMN), but results are contradictory. Sixty-six prospectively collected CMN patients were analyzed for NRASQ61 mutations using Sanger sequencing. Negative cases were evaluated for BRAFV600E mutation. NRASQ61 mutations affected 51 patients (77.3%), and BRAFV600E was found in 5 (7.6%). NRASQ61 mutation affected 29 (80.6%) of 36 giant, 16 (80.0%) of 20 large, and 5 (62.5%) of 8 medium-size CMN; BRAFmutation 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 BRAFV600E in 2 (12.5%), P= 0.009. Two patients were negative for both mutations (12.5%). In conclusion, although NRASQ61 mutations predominate, BRAFV600E mutation also affects patients with large/giant CMN (L/GCMN), and with NCM, a novel finding. BRAFV600E is also associated with increased dermal/subcutaneous nodules. These findings open the possibility of BRAF-targeted therapy in some L/GCMN and NCM cases.