BRAF and cancer: The transforming potential of oncogenes, including mutant BRAF, can be counteracted by cell cycle arrest and senescence as protective fail-safe mechanisms, such that genetic inactivation of cell cycle inhibitors is often selected for during cancer pathogenesis.56 In HCL, p27 protein expression is absent or weak in 100% of patients,52 pointing to additional mechanisms of CDKN1B silencing beyond gene mutations.