Proteogenomic analysis of pediatric and AYA high-grade glioma reveals age-dependent biology, female-male differences, and kinase targets.
Publication/Presentation Date
9-17-2026
Abstract
High-grade gliomas (HGGs) in children and adolescents and young adults (AYA) exhibit distinct biology across the neurodevelopmental spectrum. To dissect tumor-intrinsic molecular characteristics independent of developmental variation, we perform comprehensive proteogenomic analyses of tumors from 112 HGG patients aged 0-40 years. Our multi-omics analysis identifies two AYA subgroups-adolescents (aged 15-26 years) and young adults (aged 26-40 years)-with distinct molecular profiles and survival outcomes. Tumor-normal comparisons and survival modeling highlight roles of oxidative phosphorylation and neuronal system biology in glioma progression. Causal network analysis and cell line studies provide a rationale for personalized therapies targeting candidate kinases, such as CDK8. Survival modeling, clustering, and immune-landscape analyses identify proteins, post-translational modifications, and immune signatures linked to outcomes and reveal clinically relevant differences between male and female patients.
First Page
103024
Last Page
103024
ISSN
2666-3791
Published In/Presented At
Tignor, N. L., Koptyra, M., Chowdhury, S., Petralia, F., Gritsenko, M. A., Ma, W., Zhu, Y., Marino, G. B., Song, X., Migliozzi, S., Whiteaker, J. R., Rykunov, D., Hu, Y., Hosseini, N., Rokita, J. L., da Veiga Leprevost, F., Rathi, K. S., Chen, L., Wang, Y. T., Weitz, K. K., … Clinical Proteomic Tumor Analysis Consortium (2026). Proteogenomic analysis of pediatric and AYA high-grade glioma reveals age-dependent biology, female-male differences, and kinase targets. Cell reports. Medicine, 103024. Advance online publication. https://doi.org/10.1016/j.xcrm.2026.103024
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
42753723
Department(s)
Administration and Leadership
Document Type
Article