Receptor tyrosine kinases (RTKs) upregulation, secondary mutations of NRAS and KRAS, BRAF amplifications (through either extrachromosomal DNA or intra-chromosomal homogeneously staining regions), or mutations with splice variants, C-RAF or A-RAF overexpression and MEK1/2 mutations have been previously described in melanoma as possible alterations responsible for this MAPK signaling restoration [74,75]. This evidence concerns the gene BRAF and melanoma.