Uncovering the role of LINE-1 in the evolution of lung adenocarcinoma.

ABSTRACT: Understanding lung cancer evolution can identify tools for intercepting its growth^1,2. Here, in a landscape analysis of 1,024 lung adenocarcinomas (LUADs) with deep whole-genome sequencing integrated with multiomic data, we identified 542 LUADs with a diverse clonal architecture. In this group, we observed divergent evolutionary trajectories based on tobacco smoking exposure, ancestry and sex. LUAD from smokers showed an abundance of tobacco-related C:G>A:T driver mutations³ in KRAS and short subclonal diversification. LUAD in people who have never smoked (hereafter, never-smokers) showed early occurrence of copy-number alterations and EGFR mutations associated with SBS5 and SBS40a mutational signatures. Tumours containing EGFR mutations exhibited long latency, partic

SUBMITTER: Zhang T 

PROVIDER: S-EPMC12823094 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature