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Fig. 3 | Acta Neuropathologica Communications

Fig. 3

From: Novel targetable FGFR2 and FGFR3 alterations in glioblastoma associate with aggressive phenotype and distinct gene expression programs

Fig. 3

Gene expression programs in FGFR glioblastoma. a Vertical slice chart representing the ensemble of ≥ fivefold overexpressed genes from FGFR tumors classified in functional categories. The number of genes in each functional category is shown. b Venn diagram depicting the sharing of the same gene ensemble as in a between FGFR2 tumors (Res1/F2↑ and LMS4/F2T2↑) and the FGFR3 subgroup. Horizontal-slice charts of functional gene categories are shown for each of the 7 Venn diagram subsets. c Venn diagram of the ≥ fivefold overexpressed genes for the three FGFR3 cases with available RNA expression data: M60 and F72, sharing the FGFR3-TACC3 (F3T3) fusion, and F75 showing FGFR3-TLN1 (F3TLN1) fusion. The overexpressed genes from the two M60 amplified loci on chromosome 12 were not included in the expression analysis except for PTHLH, which encodes the hormone responsible for the hypercalcemia of malignancy. The functional gene categories or examples of genes associated with different Venn diagram subsets are shown boxed, with kinases, in magenta, and transcription factors, in blue. d Color-coded floating-bar graph for G1-, S- and M-phase and checkpoint (Cp) cell cycle genes. Fold-overexpression heatmaps are shown for cyclins/CDKs, and for CDK inhibitors. The corresponding CDKs inhibited by each inhibitor are listed. e Fold-overexpression heatmap of selected proliferation enzymatic therapeutic targets and MKI67. f Diagram and fold-overexpression heatmap of the BRCA1/2 DDR complex. Red and green arrows show recruitment to and repair of DNA damage, respectively; genes in blue are not overexpressed. g Venn diagram with representative examples of overexpressed transcription factors. h Mean ± SEM mRNA expression graph for intermediate filament genes. i, j Fold-overexpression heatmaps for the GPCR and Kinase functional categories. RTKs are boxed. k Mean ± SEM graph showing FGFR3 and FGF1-2 mRNA fold expression levels. CNV analysis showed normal 2-copy complement for FGFR3, and loss of one copy for FGF2 for all F48 tumors. FGF1 showed loss of one copy in F2↑ and F2T2↑, and normal complement in LG DIS6 control

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