Aberrant basal cell clonal dynamics shape early lung carcinogenesis
Menée à l'aide de modèles murins de carcinome épidermoïde du poumon et menée à l'aide d'échantillons tissulaires d'origine humaine, cette étude met en évidence un mécanisme par lequel une expansion clonale anormale de cellules basales présentant de nombreuses mutations favorise la carcinogenèse
Preinvasive squamous lung lesions are precursors of lung squamous cell carcinoma (LUSC). The cellular events underlying lesion formation are unknown. Using a carcinogen-induced model of LUSC with no added genetic hits or cell type bias, we find that carcinogen exposure leads to non-neutral competition among basal cells, aberrant clonal expansions, and basal cell mobilization along the airways. Ultimately, preinvasive lesions develop from a few highly mutated clones that dominate most of the bronchial tree. Multi-site sequencing in human patients confirms the presence of clonally related preinvasive lesions across distinct airway regions. Our work identifies a transition in basal cell clonal dynamics, and an associated shift in basal cell fate, as drivers of field cancerization in the lung.
Science , résumé 2025