This is a clinically observed cancer mutation17 that is also adjacent to a hotspot location (R80).18 In addition, relative to wild-type CDKN2A, P81L is functionally defective when overexpressed in melanoma cells.19 The post-treatment tumor from a second enzalutamide-resistant patient (Enza-2) had chr7q (spanning CDK6), whereas AR amplification was detected at both time points (Fig 5). The gene discussed is CDKN2A; the disease is cancer.