ALK and non-small cell lung carcinoma: EGFR T790M—the exemplary “gatekeeper” resistance mechanism to first-generation EGFR tyrosine kinase inhibitors—should always be seen in cis with another EGFR driver mutation like L858R or exon 19 nonframeshift deletion.32 Resistance to anti-ALK targeted therapies in NSCLC manifests as missense mutations (most frequently as L1196M and G1269A), but always in cis with sequence data indicating an ALK fusion event.33 The capability to determine cis/trans status partly relies on sophisticated bioinformatic methods and partly on assay design.