Strikingly, in an independent MSK-IMPACT cohort with heavily pretreated advanced and metastatic HNSCC, we cross-validated that MAPK pathway mutations (with nine MAPK pathway members sequenced therein: H/N/K-RAS, A/B-RAF, RAF-1, MAP2K1/2, and MAPK1) were also prognostic of favorable HNSCC patient outcome (Fig 1F). This evidence concerns the gene MAP2K1 and head and neck squamous cell carcinoma.