The most frequent mutation occurs in the 600th codon of BRAF (50% of cases). BRAF is normally involved in cell growth and this specific mutation renders the protein constitutively active and independent of normal physiological regulation, thus fostering tumor growth. RAS genes (NRAS, HRAS and KRAS) are also recurrently mutated (30% of TCGA cases) and mutations in the 61st or 12th codons trigger oncogenic activity. Loss-of-function mutations often affect tumor suppressor genes such as NF1, TP53 and CDKN2A. Other oncogenic alterations include fusions involving various kinases such as BRAF, RAF1, ALK, RET, ROS1, NTRK1., NTRK3 and MET BRAF, RAS, NF1 mutations and kinase fusions are remarkably mutually-exclusive, as they occur in different subsets of patients. Assessment of mutation status can therefore improve patient stratification and inform targeted therapy with specific inhibitors.