Fig. 2.

CIC fusions transcriptionally control negative regulators of MAPK signaling. (A) Structural alignment of WT CIC, CIC-DUX4, and CIC-NUTM1 demonstrating conserved functional domains. (B) Unsupervised PCA discriminates sarcoma samples harboring CIC-DUX4 (n = 6), CIC-NUTM1 (n = 5), or EWSR1-FLI1 (n = 5) oncoprotein-driven transcriptional signatures. (C) Hierarchical clustering analysis was conducted using 1,170 differentially expressed genes (absolute log₂[fold change] ≥1 and FDR <0.05) in sarcoma samples harboring CIC-DUX4, CIC-NUTM1, or EWSR1-FLI1 fusion oncoproteins. The color key for gene expression levels (z-score) is shown to the right of the heat map. (D) Boxplots demonstrating the expression of negative MAPK regulators DUSP6 and DUSP4 in tumors bearing CIC-DUX4 (blue), CIC-NUTM1 (yellow), or EWSR1-FLI1 (gray) oncoproteins. The distribution of expression (TPM; normalized reads from RNA-seq) in each group is displayed as median (horizontal line inside box), 25th percentile (bottom line of the box), and 75th percentile (top line of the box). The whisker vertical line shows minimum and maximum expression level. Statistical significance for the difference was evaluated by one-way ANOVA.