(A) Fraction of downstream targets with CNAs in regulators. Targets of UC-t and EM-t regulators are more likely to be affected by CNAs than targets of UC/EM-i regulators. (B) Percentage of differentially expressed target genes with amplifications. UC and EM target genes are more likely to be upregulated after amplifications compared to younger, mammal-specific genes (Jonckheere-Terpstra decreasing trend test p-value: 0.0028). A similar trend is found for the downregulation of deleted genes (Figure 4—figure supplement 2). (C) Median percentage of differentially expressed CNA genes per regulator class across tumors. Amplified and deleted target genes of UC-t regulators are more likely to be differentially expressed (median 78.27% and 75.00%, respectively), whereas few CNA target genes of UC/EM-i regulators are DE (median 21.05% and 23.33%, respectively). Deleted targets of EM-t regulators are more likely to be downregulated (50.00%) than amplifications are upregulated (33.33%). No preference is evident for targets of UC/EM-i regulators. (D) Fraction of target genes with CNAs when their regulators are CNA or CNN. A higher fraction of target genes are CNA when UC-t and EM-t regulators are CNN than when they are CNA (Wilcoxon test p=1.36×10−7 and p=1.11×10−42, respectively), indicating a preference for the alteration of targets of these regulators. However, UC/EM-i regulators display the opposite trend, although not significant. (E) Difference in the fraction of downstream targets altered by CNAs when their regulators are CNN or CNA. Values less than 0 indicate a higher fraction of CNA targets when the regulator is CNN. This trend is evident across UC-t regulators (71.70%) and EM-t regulators (71.30%), but not for UC/EM-i regulators (28.72%).