Fig. 2
Genetic and transcriptional phenotypes of GBM patients and their GSCs. A Circos plot reporting genomic copy number variation (CNV) profiling, and the relative cytobands involved, for high-grade tissues and their derivative GSCs displaying the differences retrieved in alteration frequency among subtypes, as emerged from GISTIC analysis. In each case, the outer track provides alterations in proneural samples, inside the circle those of classical cases and the inner track shows variations shared by all the mesenchymal samples. -log10(q-value) of the significant region of amplification or deletion is reported in red or blue, respectively. B Heat map of one-way hierarchical clustering of 51 differentially enriched genes in GSCs lines clearly outlining three distinctive clustering in an unsupervised manner. A dual-color code represents genes up- (red) and down-regulated (blue), respectively. C Hierarchical clustering analysis using 24 over-represented altered pathways in GBM patients and their GSCs reporting that TCGA-MS cases mainly displayed aberrations in immune system, DNA replication and TNFR1 pathways, whereas TCGA-CL ones in calcium signaling, ERBB network signaling, necrosis and apoptosis functions. TCGA-PN samples were instead mainly characterized by aberrant cellular homeostasis, differentiation of oligodendrocytes and neuroglia, activation of dendritic cells pathways. GBM subtypes are coded by color. Pathways are colored in shades of red according to the different level of significance. D Unsupervised hierarchical clustering using 66 significant differently enriched biological processes associated to gained or lost genes in GBM patients and their derivative GSCs lines across subtypes, as emerged from IPA analysis. GBM subclusters are coded by color. Pathways are colored in shades of red according to the different level of significance. E Bubble plots showing that over-represented genes and their biological process ranked by FDR in TCGA-MS GSCs are predominantly related to cell movement and migration, whereas those over-expressed in TCGA-CL and TCGA-PN cells are mostly entailed with cell proliferation and neurogenesis, respectively. The enrichment in each cluster is relative to one another. The size of the circles represents -log10 (P-value) while the colors correspond to positive (blue) or negative (red) z-score