Other mutations frequently observed in human cancers regard the RAF isoform BRAF. In >90% of cases, the substitution of valine 600 by a glutamic acid residue (V600E) leads to a constitutively active kinase independent of upstream RAS signaling, while other BRAF mutations still require post-translational dimerization but also function independent of upstream signaling (102). This evidence concerns the gene RAF1 and cancer.