Supplementary Figure 2: IMPDH2 mRNA is upregulated in murine and human GBM.

a, Schema showing replication-competent avian sarcoma-leukosis (RCAS)/tv-a system to induce glioma. To investigate the molecular mechanism underlying the metabolic GTP switch, we took advantage of ten genetically different, clinically relevant glioma mice generated by using the RCAS/tv-a system⁶⁰. In addition to Impdh2, GMP synthetase (Gmps), which converts IMPDH-produced XMP to GMP, is also upregulated. Hprt1, an essential enzyme for salvage GTP biosynthesis, is downregulated. In contrast, adenine phosphoribosyltransferase (Aprt), a critical enzyme for salvage ATP biosynthesis, and AMP deaminase-3 (Ampd3), which converts AMP to IMP, are upregulated. Together with the Impdh2 upregulation in GBM, these results suggest that a systematic change in salvage pathways occur in GBM to decrease GTP salvage and increases ATP salvage production. b, IMPDH2 mRNA is upregulated in human GBM patients. Analyses of five different GBM database on the indicated genes are shown. Similar to the results of the above murine glioma transcriptome analysis, IMPDH2, GMPS, and APRT mRNA are is upregulated in GBM, while HPRT1 and AMPD2 are downregulated. IMPDH1 mRNA expression levels in GBM are similar to normal brain tissue with some variety. TCGA/RNA-seq (n=160), Rembrandt (n=537), Gravendeel (n=284), Gill (n=92), Murat (n=84). Boxplots were derived from GlioVis website. Boxplots follow a Turkey style, in which lower and upper hinges correspond to the first and third quartiles based on their R source file for GlioVis (https://github.com/msquatrito/shiny_GlioVis/blob/master/server.R#L1, version Apr 3, 2018). c, Coordinated metabolic reprograming of purine biosynthesis pathway with IMPDH2 in GBM. Correlation analysis of representative genes in purine synthesis pathway. Plots indicate gene expression data from TCGA glioblastoma patients (HG-U133A platform, n=538). Pearson’s correlation coefficient (R) values are shown. P-values (two-sided) were calculated using the t-distribution with n-2 degrees of freedom.