Higher frequencies of somatic alterations in aggressive than indolent ATL. Aggressive (acute and lymphoma subtypes) ATL shows (A) a higher number of coding mutations identified in whole-exome/genome sequencing (n = 83), (B) a higher number of significant mutations in targeted capture sequencing (n = 414), (C) increased ploidy (n = 463), higher numbers of (D) significant focal amplifications and (E) deletions (n = 463), and (F) hypermethylation at promoter-associated cytosine guanine dinucleotide islands (n = 109) compared with indolent ATL (chronic and smoldering subtypes). P < .001 for all comparisons between aggressive and indolent subtypes by Brunner-Munzel test. Comparison of frequencies of (G) driver mutations and (H) focal CNAs between aggressive and indolent ATL (Fisher’s exact test with Benjamini–Hochberg correction). Recurrently mutated genes (n = 28) present in >3% of ATL cases and highly significant (residual Q < 10⁻¹³) focal amplifications (n = 4) and deletions (n = 20) are shown. (I) A multivariate logistic regression analysis identifying independent significant factors (present in >10%) for aggressive subtypes (vs indolent subtypes) in 414 ATL cases. CI, confidence interval; OR, odds ratio; SNV, single nucleotide variant.