Extended Data Fig. 3: TKI-resistant clones that evolve from drug-tolerant persister cells accumulate APOBEC mutations.

a, Number and percentage of TCT>TGT and TCA>TGA mutations that are highly specific for APOBEC⁴³ in early (E) and late (L) resistant clones (bar: median, two-sided Mann Whitney test). b, Number of omikli (n = 2, 3, or 4 mutations with an intermutational distance < 1 kb) and kataegis (n >= 5 mutations with an intermutational distance of < 1 kb) mutation clusters in early and late resistant clones. c, Shared and private mutations in early and late resistant clones. Shared mutations in early resistant clones refer to mutations shared across early clones from one individual. Private mutations in resistant clones refer to mutations observed in only one sample of an individual and are not shared across other samples. d, Phylogenetic tree depicting evolutionary relationships of early and late resistant clones based on pattern of shared and private mutations. e, Mutational signatures of private and shared mutations in PC9 early and late resistant clones. Late resistant clones exhibited significantly higher private APOBEC mutation percentage compared to early resistant clones (two-sided Mann Whitney test). f, Relationship between timing of EGFR^T790M mutation, TKI treatment and APOBEC mutational signatures for shared and private mutations.