Strikingly, the only gene whose alterations were associated with worse overall survival across all types of localized soft tissue sarcomas was CDKN2A. These results suggest there is broad biological importance of the p16INK4a-CDK4/6-RB1 pathway and/or ARF signaling pathways in sarcoma pathogenesis, bolstering emerging evidence supporting the use of FDA-approved, CDK-targeted therapies for sarcoma treatment. The gene discussed is CDKN2A; the disease is sarcoma.