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. 2020 Oct 15;22(11):644–658. doi: 10.1016/j.neo.2020.07.001

Supplementary figure 2.

Supplementary figure 2

Fbxw7 loss results in the dysregulation of E2F, c-Myc, DNA repair, G2/M checkpoint, and mitotic spindle genes. A. GSEA analysis was performed on bulk RNA sequencing data from non-tumor epithelial (epis) cells. Genesets that were enriched in the Fbxw7-/- cells vs. the Fbxw7+/+ cells included DNA repair genes (left) and G2M checkpoint genes (right). B. GSEA was performed on WT mammary tissue vs. Fbxw7-/- tumors. Similar to Fbxw7-/- nontumor epithelial cells, tumor samples were enriched for DNA repair genes (left) and G2M checkpoint genes (middle), however, an increase in the normalized enrichment score (NES) was observed. Enrichment of an additional geneset, mitotic spindle genes (right) was also observed in the tumor samples. C. GSEA was performed on Fbxw7+/+ epithelials vs. tumors. Genesets that were enriched in the tumor samples included E2F (left) and c-Myc targets (second from left) as well as G2M checkpoint (third from left) and DNA repair pathways (right). D. GSEA was performed on Fbxw7-/- epithelials vs. tumors. The E2F pathway was enriched in the tumor samples. E. GSEA was performed on Fbxw7-/- tumors vs. MMTV-PyMT 8 week tumors (19). The E2F and c-Myc pathways were enriched in the Fbxw7-/- tumor samples. For all GSEA analyses, only those genesets that met the cutoff of p<0.01 and an FDR of <25% were considered.