Copy number and SV landscapes in therapy-related myeloid neoplasms. (A) Cumulative copy number profile for all de novo samples (n = 316; 18 genomes from TCGA, 298 exomes from Beat AML) and 39 tMN genomes. tMN genomes are split into chemotherapy signature-positive (n = 17) and -negative (n = 22) cases. GISTIC peaks and CNA arm-level events enriched in tMN with chemotherapy signatures (P < .05; FDR < 0.1; Fisher test) are annotated with an asterisk for significance compared with: tMN without chemotherapy signatures. (B) SV landscape across de novo AML genomes from TCGA (n = 18) and tMN genomes with and without a chemotherapy-associated mutational signature. Breakpoints are binned into 1 megabase segments. Simple events point upward from the x-axis and complex events (eg, chromothripsis) point downward. (C) Plot of cumulative copy number changes and SV chromothriptic breakpoints responsible for focal multigain events in SMARCA4. (D) Growth curves of SMARCA4 transfected Ba/F3 cells versus cells transfected with the vector in the interleukin-3 cytokine independence assay. ****P < .0001.