NF1 and melanoma: Particularly, they showed that inactivating NF1 mutations were present in 46% of melanomas expressing WT-BRAF and NRAS, occurred in older patients, were associated with a higher mutational burden, and showed a peculiar pattern of co-mutation with other RASopathy genes (particularly RASA2) and with RAC1 and ARID2. NF1 encodes a negative RAS regulator, and therefore it is not surprising that NF1-inactivating mutations led to increased RAS activation.