Nicole L Tignor, Mateusz Koptyra, Shrabanti Chowdhury, Francesca Petralia, Marina A Gritsenko, Weiping Ma, Yuankun Zhu, Giacomo B Marino, Xiaoyu Song, Simona Migliozzi, Jeffrey R Whiteaker, Dmitry Rykunov, Yingwei Hu, Noshad Hosseini, Jo Lynne Rokita, Felipe da Veiga Leprevost, Komal S Rathi, Lijun Chen, Yi-Ting Wang, Karl K Weitz, Rosalie K Chu, Ronald J Moore, Azra Krek, Weijia Fu, Xuran Wang, Eden Z Deng, Chia-Feng Tsai, Tyler Sagendorf, Vladislav A Petyuk, Tujin Shi, Thomas L Fillmore, Rui Zhao, Matthew E Monroe, Marius V Dannappel, Paul Daniel, Lei Zhao, Richard G Ivey, Uliana J Voytovich, Tomer M Yaron-Barir, Emily M Huntsman, Jared L Johnson, Nakib Abedin, Yan-Chak Li, Mariarita Santi, Demetri Dupal, Jena Lilly, Adam Kraya, Joseph M Dybas, Bo Zhang, Chuwei Zhong, Miguel A Brown, Saksham Phul, Eric Wafula, Alvin Farrel, Zhuangzhuang Geng, Ryan J Corbett, Ammar S Naqvi, Daniel P Miller, Jennifer Mason, Tatiana S Patton, Stephanie McGrory, Shannon Robins, Allison Heath, Catherine Sullivan, Noel Coleman, Allison Morgan, Luciano Garofano, Boris Reva, Eric E Schadt, Richard D Smith, Mehdi Mesri, Ana I Robles, Lewis C Cantley, Li Ding, Karin D Rodland, Bing Zhang, Alexey I Nesvizhskii, Antonio Iavarone, Marcin Cieslik, Joseph E Ippolito, Phillip B Storm, Joshua B Rubin, Ron Firestein, Avi Ma'ayan, Hui Zhang, Amanda G Paulovich, Tao Liu, Adam Resnick, Brian R Rood, Pei Wang, Philadelphia Coalition for a Cure, Children’s Brain Tumor Network, Clinical Proteomic Tumor Analysis Consortium
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.