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. 2024 Apr 8;84(9):1426–1442. doi: 10.1158/0008-5472.CAN-23-3334

Figure 2.

Figure 2. EWSR1::WT1 induces distinct transcriptional alterations. A, Volcano plots of RNA-seq data from dox-inducible shWT1 DSRCT cell lines treated with or without dox (n = 2). Red, significantly upregulated; blue, significantly downregulated. P < 0.05. B, Venn diagrams comparing genes upregulated and downregulated by EWSR1::WT1 in JN-DSRCT-1 (red), BER-DSRCT (green), BOD-DSRCT (purple), and SK-DSRCT2 (yellow). C, Top 15 overrepresented pathways among EWSR1::WT1 upregulated genes in each DSRCT cell line. D, Heatmap of log2-fold change in gene expression caused by (i) knockdown of EWSR1::WT1 in DSRCT cell lines or (ii) knockdown of WT1 in leukemia (Kasumi, FLT3-IDT), primary CD34 cells, or breast cancer (MDA-MB-157). E, Heatmap of log2-fold change in gene expression caused by knockdown of fusion oncoproteins in DSRCT, EWS, SS, and CCS cell lines. F, GSEA of EWSR1::WT1 downregulated genes in EWS, SS, or CCS, with their respective fusion oncoproteins depleted. ***, P < 0.001; ns, nonsignficant.

EWSR1::WT1 induces distinct transcriptional alterations. A, Volcano plots of RNA-seq data from dox-inducible shWT1 DSRCT cell lines treated with or without dox (n = 2). Red, significantly upregulated; blue, significantly downregulated. P < 0.05. B, Venn diagrams comparing genes upregulated and downregulated by EWSR1::WT1 in JN-DSRCT-1 (red), BER-DSRCT (green), BOD-DSRCT (purple), and SK-DSRCT2 (yellow). C, Top 15 overrepresented pathways among EWSR1::WT1 upregulated genes in each DSRCT cell line. D, Heatmap of log2-fold change in gene expression caused by (i) knockdown of EWSR1::WT1 in DSRCT cell lines or (ii) knockdown of WT1 in leukemia (Kasumi, FLT3-IDT), primary CD34 cells, or breast cancer (MDA-MB-157). E, Heatmap of log2-fold change in gene expression caused by knockdown of fusion oncoproteins in DSRCT, EWS, SS, and CCS cell lines. F, GSEA of EWSR1::WT1 downregulated genes in EWS, SS, or CCS, with their respective fusion oncoproteins depleted. ***, P < 0.001; ns, nonsignficant.