biostudies-literatureFu FNational Natural Science Foundation of ChinaNational Natural Science Foundation of China (National Science Foundation of China)1037-1055https://www.ebi.ac.uk/biostudies/studies/S-EPMC12689645biostudies-literatureUnknown35(12)Lung adenocarcinoma (LUAD) progresses from pre-invasive to invasive stages, as well as from ground-glass opacities (GGOs) to solid nodules. However, the dynamic genomic and transcriptomic changes underlying LUAD progression are incompletely understood. Here, we performed whole-genome and transcriptome sequencing on 1008 LUAD samples from 954 patients who underwent surgery at Fudan University Shanghai Cancer Center, with comprehensive follow-up data. There was one atypical adenomatous hyperplasia, 42 adenocarcinomas in situ, 116 minimally invasive adenocarcinomas, and 849 invasive adenocarcinomas spanning all pathological stages. EGFR was the most frequently mutated gene in the study cohort, followed by TP53, RBM10, KRAS, and KMT2D. Mutation frequencies of tumor suppressor genes, such as TPCell researchGenomic and transcriptomic dynamics in the stepwise progression of lung adenocarcinoma.PMC126896458243009982373309Yang JZheng YShi LPan YJiang HShang JXiang JGao JYe TLin YChen HYan YYuan HWang JLi YFu FZhang YCao ZHu HHan HGao ZJin LfalseGenomic and transcriptomic dynamics in the stepwise progression of lung adenocarcinoma.Lung adenocarcinoma (LUAD) progresses from pre-invasive to invasive stages, as well as from ground-glass opacities (GGOs) to solid nodules. However, the dynamic genomic and transcriptomic changes underlying LUAD progression are incompletely understood. Here, we performed whole-genome and transcriptome sequencing on 1008 LUAD samples from 954 patients who underwent surgery at Fudan University Shanghai Cancer Center, with comprehensive follow-up data. There was one atypical adenomatous hyperplasia, 42 adenocarcinomas in situ, 116 minimally invasive adenocarcinomas, and 849 invasive adenocarcinomas spanning all pathological stages. EGFR was the most frequently mutated gene in the study cohort, followed by TP53, RBM10, KRAS, and KMT2D. Mutation frequencies of tumor suppressor genes, such as TP2025-01-01T00:00:00Z2025 Dec2026-06-05T23:57:13.703Z2026-05-23T03:13:55.94ZS-EPMC126896454134554410.1038/s41422-025-01200-w