Supplementary Figures 1-15 from Clinical efficacy of ONC201 in H3K27M-mutant diffuse midline gliomas is driven by disruption of integrated metabolic and epigenetic pathways
Year: 2024
Type: supplementary-materials
Abstract: Contains supplementary data and table titles and as well as supplementary figures with associated titles and legends. Fig. S1. Selection method for planned efficacy analysis of ONC201 in patients with H3K27MDMG. Fig. S2. Progression-free survival from diagnosis of trial patients with non-recurrent H3K27MDMG treated with ONC201. Fig. S3. Swimmers’ plot of ONC201 response by recurrence status, tumor location, and ONC201 trial. Fig. S4. ONC201 efficacy is independent of TP53 mutation status and chromosomal instability. Fig. S5. Cox proportional hazard regression to assess the effect of ONC201 after adjusting for confounders. Fig. S6. Survival of patients with H3K27M-DMG treated with ONC201 versus ONC201untreated historical controls. Fig. S7. Survival of patients with H3K27M-DMG treated with ONC201 versus ONC201untreated patients (PNOC003 or HERBY Phase II trials). Fig. S8. Molecular attributes of patients with H3K27M-DMG treated with ONC201. Fig. S9: Survival of H3K27M-DMG mice models treated with ONC201. Fig. S10. Integrative analysis of in vitro and human tumor metabolic gene expression in response to ONC201. Fig. S11. ONC201-mediated L2HG production increases H3K27me3 in H3K27M-DMG cells. Fig. S12. ONC201-induced increase in H3K27me3 is mediated by lactate dehydrogenase. Fig. S13. ONC201 alters genomic chromatin accessibility and H3K27ac distribution in H3K27M-DMG cells. Fig. S14. ONC201 increases global H3K27me3 in patient samples. Fig. S15. ONC201 does not cause hypermethylation leading to a glioma CpG island methylator phenotype.
Authors: Sriram Venneti, Abed Rahman Kawakibi, Sunjong Ji, Sebastian M. Waszak, Stefan R. Sweha, Mateus Mota, Matthew Pun, Akash Deogharkar, Chan Chung, Rohinton S. Tarapore, Samuel Ramage, Andrew Chi, Patrick Y. Wen, Isabel Arrillaga-Romany, Tracy T. Batchelor, Nicholas A. Butowski, Ashley Sumrall, Nicole Shonka, Rebecca A. Harrison, John de Groot, Minesh Mehta, Matthew D. Hall, Doured Daghistani, Timothy F. Cloughesy, Benjamin M. Ellingson, Kevin Beccaria, Pascale Varlet, Michelle M. Kim, Yoshie Umemura, Hugh Garton, Andrea Franson, Jonathan Schwartz, Rajan Jain, Maureen Kachman, Heidi Baum, Charles F. Burant, Sophie L. Mottl, Rodrigo T. Cartaxo, Vishal John, Dana Messinger, Tingting Qin, Erik Peterson, Peter Sajjakulnukit, Karthik Ravi, Alyssa Waugh, Dustin Walling, Yujie Ding, Ziyun Xia, Anna Schwendeman, Debra Hawes, Fusheng Yang, Alexander R. Judkins, Daniel Wahl, Costas A. Lyssiotis, Daniel de la Nava, Marta M. Alonso, Augustine Eze, Jasper Spitzer, Susanne V. Schmidt, Ryan J. Duchatel, Matthew D. Dun, Jason E. Cain, Li Jiang, Sylwia A. Stopka, Gerard Baquer, Michael S. Regan, Mariella G. Filbin, Nathalie Y.R. Agar, Lili Zhao, Chandan Kumar-Sinha, Rajen Mody, Arul Chinnaiyan, Ryo Kurokawa, Drew Pratt, Viveka N. Yadav, Jacques Grill, Cassie Kline, Sabine Mueller, Adam Resnick, Javad Nazarian, Joshua E. Allen, Yazmin Odia, Sharon L. Gardner, Carl Koschmann
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4402805074