Zoom link: https://snu-ac-kr.zoom.us/j/84501731770

Title:　Proteogenomic Characterization of Korean Never-Smoker　Lung Adenocarcinoma harboring rare or unknown driver oncogenes

Abstract

Lung cancer patients with frequent mutations are well-characterized and have diverse therapeutic options. However, patients in the margin of current proteogenomic knowledge have only a few therapeutic options. We characterized the proteogenomic landscape of 141 never-smoking lung adenocarcinoma (NSLA) patients without known driver oncogene alterations, including EGFR mutation and ALK fusion. TP53 showed the highest mutation frequency among known oncogenes in our cohort. We found that TP53 mutations induced the upregulation of S100A9 protein expression and phosphorylation. Copy number changes in BRD9 significantly affected genes associated with metabolic and immunogenic pathways, which were driven by the trans effect. Comprehensive proteogenomic characterization revealed a novel subtype (TRU-M) of NSLA distinguished by poor prognosis and enrichment of minor mutations in TP53 or KRAS, including KRAS G12V and G12D. Mutational signature analysis suggested that alkylating agents are key environmental carcinogens responsible for the onset of NSLA in Korean patients and EGFR mutations potentiated these effects. Our multiomics dataset may help researchers and clinicians with the management of NSLA patients without prior knowledge of driver events.