| Title | Proteogenomic analysis of pediatric and AYA high-grade glioma reveals age-dependent biology, female-male differences, and kinase targets. |
| Publication Type | Journal Article |
| Year of Publication | 2026 |
| Authors | Tignor NL, Koptyra M, Chowdhury S, Petralia F, Gritsenko MA, Ma W, Zhu Y, Marino GB, Song X, Migliozzi S, Whiteaker JR, Rykunov D, Hu Y, Hosseini N, Rokita JLynne, Leprevost Fda Veiga, Rathi KS, Chen L, Wang Y-T, Weitz KK, Chu RK, Moore RJ, Krek A, Fu W, Wang X, Deng EZ, Tsai C-F, Sagendorf T, Petyuk VA, Shi T, Fillmore TL, Zhao R, Monroe ME, Dannappel MV, Daniel P, Zhao L, Ivey RG, Voytovich UJ, Yaron-Barir TM, Huntsman EM, Johnson JL, Abedin N, Li Y-C, Santi M, Dupal D, Lilly J, Kraya A, Dybas JM, Zhang B, Zhong C, Brown MA, Phul S, Wafula E, Farrel A, Geng Z, Corbett RJ, Naqvi AS, Miller DP, Mason J, Patton TS, McGrory S, Robins S, Heath A, Sullivan C, Coleman N, Morgan A, Garofano L, Reva B, Schadt EE, Smith RD, Mesri M, Robles AI, Cantley LC, Ding L, Rodland KD, Zhang B, Nesvizhskii AI, Iavarone A, Cieslik M, Ippolito JE, Storm PB, Rubin JB, Firestein R, Ma'ayan A, Zhang H, Paulovich AG, Liu T, Resnick A, Rood BR, Wang P |
| Corporate Authors | Philadelphia Coalition for a Cure, Children’s Brain Tumor Network, Clinical Proteomic Tumor Analysis Consortium |
| Journal | Cell Rep Med |
| Pagination | 103024 |
| Date Published | 2026 Sep 17 |
| ISSN | 2666-3791 |
| 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. |
| DOI | 10.1016/j.xcrm.2026.103024 |
| Alternate Journal | Cell Rep Med |
| PubMed ID | 42753723 |