Genes differentially expressed in short survival versus long survival patients, considered according to cancer type and cancer class.

Volcano plots showing significantly downregulated (the thresholds are FDR -0.5) genes in green and red, respectively. Here short survival patients are compared with long survival patients, so in all three panels genes found to be upregulated are genes that are upregulated in short survival patients, and genes found downregulated are genes that are downregulated in short survival patients. Grey indicates genes that are not significantly downregulated or upregulated. Log of fold change (LogFC) is on the x-axis and significance level (-log10P) is on the y-axis. Panel A shows differentially expressed genes when all of the patients are considered (n = 515). Panel B shows differentially expressed genes when only patients with solid cancers are considered (n = 293), and panel C shows differentially expressed genes when only patients with blood cancers are considered (n = 222). In all panels, the significantly downregulated and upregulated genes are labelled with their Hugo Gene Nomenclature Committee (HGNC) gene symbols. The three genes (SSX1, MAGEC2 and ULBP2) that are found to be significantly differentially expressed in all three analyses are shown in bold.</p

Patients statistics.

(DOCX)</p

Additional file 8: of Metabolic characterization of isocitrate dehydrogenase (IDH) mutant and IDH wildtype gliomaspheres uncovers cell type-specific vulnerabilities

IDH1 mutant overexpression leads to high levels of 2-HG and the c227 inhibitor is an effective inhibitor of 2-HG formation. IDH wildtype gliomaspheres transduced with the IDH1 mutant enzyme (308 + IDH1mut) and endogenous IDH1 mutant cells treated with 5 μM c227 inhibitor (213 + c227) for 24 h are compared to their respective controls (308 and 213) for 2-HG levels as determined by LC-MS. Data represent the means ± SEM of three replicates per condition. (PDF 22 kb

Additional file 9: of Metabolic characterization of isocitrate dehydrogenase (IDH) mutant and IDH wildtype gliomaspheres uncovers cell type-specific vulnerabilities

IDH1 mutant enzyme does not affect glucose labeling of nucleotide precursors. Cells were treated and analyzed as described for Supporting Figure S4 in order to determine the percent labeling of nucleotide precursors. There is no significant difference when comparing IDH1 mutant overexpression or endogenous mutant inhibition to their respective controls. (PDF 64 kb

Additional file 2: of Metabolic characterization of isocitrate dehydrogenase (IDH) mutant and IDH wildtype gliomaspheres uncovers cell type-specific vulnerabilities

2-HG inhibition with c227 moderately increases DNA damage following radiation but does not reverse the IDH1 mutant phenotype to an IDH wildtype phenotype. A-B. Assessment of DNA damage and repair by comet analysis following irradiation (10 Gy). HK252 was treated for 48 h with 5 μM c227 or control prior to comet analysis and compared to the IDH WT line HK157. A. Similar analysis of tail moment length as conducted in Fig. 4. B. Graph showing the percent of cells with comets as explained in Fig. 4. All error bars represent ± SEM. (PDF 46 kb

Additional file 10: of Metabolic characterization of isocitrate dehydrogenase (IDH) mutant and IDH wildtype gliomaspheres uncovers cell type-specific vulnerabilities

Effects of pharmacologic inhibition of the IDH1 mutant enzyme on TCA cycle intermediates. Cells were analyzed as described in Supporting Figure S5. Left: Metabolites with significantly different percent glucose labeling of metabolites in the endogenous IDH1 mutant line 213 treated with c227 inhibitor or control (p < 0.05). Right: Percent labeling from endogenous IDH1 mutant and IDH wildtype groups for metabolites that were not significantly different. (PDF 206 kb

Additional file 6: of Metabolic characterization of isocitrate dehydrogenase (IDH) mutant and IDH wildtype gliomaspheres uncovers cell type-specific vulnerabilities

Glucose labeling of metabolites. Glucose fractional contribution was computed for all 159 metabolites. Metabolites that were significantly different between groups (uncorrected t test p < 0.05) are shown here. (PDF 137 kb

Additional file 8: of Metabolic characterization of isocitrate dehydrogenase (IDH) mutant and IDH wildtype gliomaspheres uncovers cell type-specific vulnerabilities

IDH1 mutant overexpression leads to high levels of 2-HG and the c227 inhibitor is an effective inhibitor of 2-HG formation. IDH wildtype gliomaspheres transduced with the IDH1 mutant enzyme (308 + IDH1mut) and endogenous IDH1 mutant cells treated with 5 μM c227 inhibitor (213 + c227) for 24 h are compared to their respective controls (308 and 213) for 2-HG levels as determined by LC-MS. Data represent the means ± SEM of three replicates per condition. (PDF 22 kb

Additional file 7: of Metabolic characterization of isocitrate dehydrogenase (IDH) mutant and IDH wildtype gliomaspheres uncovers cell type-specific vulnerabilities

Radiation leads to low levels of TUNEL staining in gliomaspheres. Representative images and quantification of cells stained for TUNEL positivity 4 days after exposure to increasing doses of radiation. There is no significant difference between groups. Error bars represent ¹ SEM. (PDF 2212 kb

Additional file 1: of Metabolic characterization of isocitrate dehydrogenase (IDH) mutant and IDH wildtype gliomaspheres uncovers cell type-specific vulnerabilities

Patient-derived gliomasphere culture characteristics. Relevant patient information and clinical characteristics for the primary, patient-derived gliomasphere cultures used in this study. Summary of selected copy-number alterations and mutations are also shown. (PDF 42 kb