NRAS and melanoma: Interestingly, the concomitant occurrence of five of the eight D594BRAF variants with mutations in KRAS or NRAS may be explained by the experimentally described synergy of kinase-dead BRAF mutations involving D594 and oncogenic RAS. Their cooperation in inducing tumor progression, indeed, has been demonstrated in a murine model of melanoma [13], thus confirming the hypothesis that the high frequency of this inactivating mutation (also observed in our MM patient cohort) is incompatible with a random event.