As dysregulation of the p16/RB1 or p14ARF/MDM2/p53 pathways may intrinsically limit the activity of BRAFi in advanced melanoma, we hypothesized that our cohort of patients with germinal CDKN2A PV may achieve suboptimal results with targeted therapy, especially those who received a BRAFi as a single agent. The gene discussed is MDM2; the disease is melanoma.