Inherited mutation in the tumor suppressor gene CDKN2A is one of the strongest known risk factors for melanoma of the skin. Moreover, carriers have been found to have poor melanoma-specific survival. In this study, responses to novel immunotherapy agents (PD-1 and CTLA-4 inhibitors) in CDKN2A mutation carriers with metastatic melanoma were evaluated. Eleven of nineteen affected carriers (58%) responded to the immunotherapy, six with complete responses (32%) which are significantly higher frequencies than observed in clinical trials (37% and 7%, respectively). Further, we report that melanoma tumors with CDKN2A mutations have significantly higher burden of mutations.CDKN2A mutated melanoma patients may have improved immunotherapy responses due to increased tumor mutational load, resulting in a stronger antitumoral immune responses. (By Dr. Hildur Helgadottir, https://jmg.bmj.com/content/early/2018/10/05/jmedgenet-2018-105610.1 )