The model of class 3 BRAF mutants by Yao et al. [24] postulates that signaling dysregulation by these mutants relies on concomitant mechanisms to support RAS activation: coexisting RAS mutations or NF1 deletions or mutations in melanomas, and RAS activation by aberrant expression or activity of receptor tyrosine kinase in epithelial tumors (lung or CRC). This evidence concerns the gene NF1 and colorectal carcinoma.