In this disease, the most frequent genetic alteration, which accounts for >60% of melanomas is the alteration of B-RAF, with a glutamic acid for valine substitution at codon 600 in exon 15 (Val600Glu; B-RAFV600E); this mutation introduces a conformational change in protein structure due to glutamic acid that acts as a phosphomimetic between the Thr598 and Ser601 phosphorylation sites, leading to constitutive activation of the protein with a large increase in the basal kinase activity; the resulting hyperactivity of the MAP kinase pathway promotes tumor development (13,18). The gene discussed is BRAF; the disease is melanoma.