Fig. 1

The H3K27M mutation influences metabolic phenotypes and the metabolic response to radiation. A Untreated intracranial DIPGXIII xenografts and contralateral normal brain issue (n=2 mice/group) were harvested, and their metabolites were collected by methanol extraction and measured using LC/MS. Data are presented as the top 25 significantly different metabolites between Tumor and NB and are ordered by difference in average median centered abundance between H3K27M and H3K27M-KO cells. B Metabolite set enrichment analysis of all metabolites whose abundance were significantly different between Tumor and normal brain (83 total). Blue bars indicate pathways important for DMG-H3K27M biology as reported in the literature. Red bars indicate pathways important for purine metabolism. C Metabolite levels in untreated BT245 isogenic cell lines as measured using LC/MS. Data represent the top 25 significantly different metabolites between H3K27M-KO and H3K27M cells. Data are ordered by difference in median centered abundance in descending order. Metabolite extractions were performed in triplicate. D and E H3K27M-isogenic cell lines DIPGXIII (D) and BT245 (E) were treated with or without 4Gy RT and harvested for metabolite quantification 2hrs later. Metabolites meeting the FC threshold were selected. Data represent the top 25 largest absolute post-RT abundance differences between H3K27M and H3K27M-KO cells in descending order. Red indicates abundances over a post-RT FC value of 0.0. Blue indicates abundances under a post-RT FC value of 0.0. F and G Metabolic set enrichment analysis was performed on the metabolite lists for DIPGXIII (D) and BT245 (E) and ordered based on –log₁₀ p-value. Red bars indicate pathways important for purine metabolism. H Venn Diagram depicting the metabolic pathways enriched in RT-treated DMG-H3K27M isogenic cell lines. Bold-faced font indicates metabolic pathways important for purine metabolism and synthesis. I Purine metabolites from DIPGXIII xenograft tumors and contralateral normal brain from A) were compared and ordered by difference in average median centered abundance between tumor and normal brain