Using our analytical approach, we showed that tumors of younger patients with NSCLC were enriched for genomic alterations in key NSCLC driver-genes including EGFR, ALK, ROS1, and NTRK1. Specific, clinically significant alterations with an associated FDA-approved targeted therapy were detected as enriched in younger patient tumors including two EGFR deletions, E746-A750 and L747-E749, and an ALK fusion, EML4-ALK. Here, EML4 is linked to non-small cell lung carcinoma.