We combine the Eml4-Alk adenovirus with lineage-tracing mouse models, DNA methylome, and single-cell RNA transcriptome analysis and demonstrate that Club cells upon Eml4-Alk fusion trans-differentiate early during tumour development, gain the expression of alveolar markers, and yield heterogeneous tumour subgroups by using their intrinsic regeneration mechanisms. The gene discussed is EML4; the disease is neoplasm.