Tumor evolutionary trajectories during the acquisition of invasiveness in early stage lung adenocarcinoma

The evolutionary trajectories of early lung adenocarcinoma (LUAD) have not been fully elucidated. We hypothesize that genomic analysis between pre-invasive and invasive components will facilitate the description of LUAD evolutionary patterns. We micro-dissected malignant pulmonary nodules (MPNs) into paired pre-invasive and invasive components for panel-genome sequencing and recognize three evolutionary trajectories. Evolutionary mode 1 (EM1) demonstrates none of the common driver events between paired components, but rather two modes, EM2 and EM3, exhibit private variants restricted to pre-invasive and invasive components, respectively. When ancestral clones harbor EGFR mutations, truncal abundance significantly decrease after the acquisition of invasiveness, which may be associated with the intracellular accumulation of infiltrated B cells. Harboring EGFR mutations is critical to the selective pressure and further impacts the prognosis. Our findings extend the understanding of evolutionary trajectories during invasiveness acquisition in early LUAD.