Despite the remarkable differences between acral and non-acral melanomas, their evolutionary trajectories converge during later progression stages, with incremental accrual of additional MAPK pathway mutations, inactivation of CDKN2A/B at the transition to the invasive stage, and the inactivation of PTEN in invasive and metastatic stages10,12 (Fig. 7). The gene discussed is CDKN2A; the disease is melanoma.