Identifying New EGFR Driver Mutations in Non-Small Cell Lung Cancer

Abstract

Lung cancer is the leading cause of cancer deaths worldwide, with a 5-year survival rate of 18%. Non-Small Cell Lung Cancer (NSCLC) represents the major histological sub-type making up 85% of all lung cancers. One oncogenic driver of NSCLC is EGFR, which is mutated in 14% of patients. Currently, a subset of EGFR mutations remains functionally uncharacterized. In this study, we sought to functionally characterize all possible EGFR mutations. To systematically assess uncharacterized mutations in EGFR, we performed a saturation mutagenesis screen, where we identified both known EGFR hotspot mutations (EGFR L858R) and potential novel EGFR driver mutations. From our screening efforts we identified EGFR I759M as a potential novel driver of EGFR oncogenesis. To validate this finding, we expressed EGFR I759M in H3122, a NSCLC cell line, and performed a population doubling assay and a cell viability assay. We also evaluated EGFR I759M protein expression using western blot analysis. Together, our preliminary findings suggest that the EGFR I759M mutation is a likely driver of EGFR oncogenesis.