YES1 amplification as a mechanism of acquired resistance (AR) to EGFR tyrosine kinase inhibitors (TKIs) identified by a transposon mutagenesis screen and clinical genomic testing.

9043 Background: Overcoming AR to EGFR TKIs remains challenging, and in many cases the mechanisms are still unclear. To identify novel mechanisms of resistance to EGFR TKIs, we performed a forward genetic screen using transposon mutagenesis in EGFR-mutant lung adenocarcinoma cells. Methods: EGFR TKI-sensitive PC9 cells were co-transfected with plasmids encoding a mutagenic piggyBactransposon and hyperactive piggyBac transposase....