Fig. 4
- ID
- ZDB-FIG-230120-5
- Publication
- Adane et al., 2021 - STAG2 loss rewires oncogenic and developmental programs to promote metastasis in Ewing sarcoma
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Loss of STAG2 alters the EWS/FLI1-driven oncogenic transcriptional program (A) Heatmap and average linkage dendrogram of genome-wide gene expression, log2(normalized counts), in STAG2 KO versus WT A673 and TC71 cells. (B?E) GSEA plots demonstrating the enrichment of the STAG2 KO versus WT gene signature for A673 cells in the genome-wide expression changes induced by STAG2 KO in (B) TC71 cells or (C?E) three distinct Ewing sarcoma primary patient tumor datasets. Normalized enrichment score, p value, and false discovery rate (FDR) are indicated in each plot. (F) Venn diagram depicting the overlap between differentially expressed genes with genes harboring a differential loop within 5 kb of their TSS. Two-tailed Fisher?s exact test, ???p < 0.001; ns, not significant. (G) Similar analysis as in (F) is shown for EWS/FLI1 anchored differential loops. Two-tailed Fisher?s exact test, ??p < 0.01; ns, not significant. (H) Scatterplot depicting the overlap between gene expression change and EWS/FLI1 binding at the nearest enhancer assessed by ChIP-seq. Two-tailed Fisher?s exact test, ????p < 0.0001, ?p < 0.05. (I) Volcano plots for GSEA enrichment scores for the genome-wide expression changes induced in A673 and TC71 and by STAG2 mutant versus STAG2 WT tumor samples from Crompton et al. (2014) versus the union of a collection of 12 EWS/FLI1 public gene signatures in A673 cells and MSigDB v7.1 c2 pathways (5,529 gene sets). (J) qRT-PCR-based validation of a subset of EWS/FLI1 target genes repressed in STAG2 KO relative to control A673 cells. Data shown as mean ± SD. |
Reprinted from Cancer Cell, 39, Adane, B., Alexe, G., Seong, B.K.A., Lu, D., Hwang, E.E., Hnisz, D., Lareau, C.A., Ross, L., Lin, S., Dela Cruz, F.S., Richardson, M., Weintraub, A.S., Wang, S., Iniguez, A.B., Dharia, N.V., Conway, A.S., Robichaud, A.L., Tanenbaum, B., Krill-Burger, J.M., Vazquez, F., Schenone, M., Berman, J.N., Kung, A.L., Carr, S.A., Aryee, M.J., Young, R.A., Crompton, B.D., Stegmaier, K., STAG2 loss rewires oncogenic and developmental programs to promote metastasis in Ewing sarcoma, 827-844.e10, Copyright (2021) with permission from Elsevier. Full text @ Cancer Cell