Peer-reviewedCC BY-NC-ND 4.0Cell Reports Medicine
Proteogenomic analysis of pediatric and AYA high-grade glioma reveals age-dependent biology, female-male differences, and kinase targets
19 affiliations
- 1Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- 2The Center for Data Driven Discovery in Biomedicine, Division of Neurosurgery, Children’s Hospital of Philadelphia, Philadelphia, PA 19146, USA
- 3Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA 99354, USA
- 4Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- 5Centre for Biomedical Data Science, Duke-NUS Medical School, National University of Singapore, Singapore 169857, Singapore
- 6Division of Clinical Genomics and Therapeutics, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA
- 7Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
- 8Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- 9Gilbert S. Omenn Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA
- 10Center for Cancer and Immunology Research, Children’s National Research Institute, Washington, DC 20012, USA
- 11Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC 20010, USA
- 12Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA
- 13Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA
- 14Centre for Cancer Research, Hudson Institute of Medical Research, Department of Molecular and Translational Science, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC 3168, Australia
- 15Meyer Cancer Center, Englander Institute for Precision Medicine, Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY 10021, USA
- 16Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
- 17Department of Cell Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
- 18Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
- 19Department of Biomedical and Health Informatics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
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.
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BibTeX
@article{tignor2026proteogenomic,
title = {{Proteogenomic analysis of pediatric and AYA high-grade glioma reveals age-dependent biology, female-male differences, and kinase targets}},
author = {Nicole L. Tignor and Mateusz Koptyra and Shrabanti Chowdhury and Francesca Petralia and Marina A. Gritsenko and Weiping Ma and Yuankun Zhu and Giacomo B. Marino and Xiaoyu Song and Simona Migliozzi and Jeffrey R. Whiteaker and Dmitry Rykunov and Yingwei Hu and Noshad Hosseini and Jo Lynne Rokita and Felipe da Veiga Leprevost and Komal S. Rathi and Lijun Chen and Yi-Ting Wang and Karl K. Weitz and Rosalie K. Chu and Ronald J. Moore and Azra Krek and Weijia Fu and Xuran Wang and Eden Z. Deng and Chia-Feng Tsai and Tyler Sagendorf and Vladislav A. Petyuk and Tujin Shi and Thomas L. Fillmore and Rui Zhao and Matthew E. Monroe and Marius V. Dannappel and Paul Daniel and Lei Zhao and Richard G. Ivey and Uliana J. Voytovich and Tomer M. Yaron-Barir and Emily M. Huntsman and Jared L. Johnson and Nakib Abedin and Yan-chak Li and Mariarita Santi and Demetri Dupal and Jena Lilly and Adam Kraya and Joseph M. Dybas and Bo Zhang and Chuwei Zhong and Miguel A. Brown and Saksham Phul and Eric Wafula and Alvin Farrel and Zhuangzhuang Geng and Ryan J. Corbett and Ammar S. Naqvi and Daniel P. Miller and Jennifer Mason and Tatiana S. Patton},
journal = {Cell Reports Medicine},
year = {2026},
month = sep,
doi = {10.1016/j.xcrm.2026.103024},
url = {https://doi.org/10.1016/j.xcrm.2026.103024},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Proteogenomic analysis of pediatric and AYA high-grade glioma reveals age-dependent biology, female-male differences, and kinase targets
AU - Nicole L. Tignor
AU - Mateusz Koptyra
AU - Shrabanti Chowdhury
AU - Francesca Petralia
AU - Marina A. Gritsenko
AU - Weiping Ma
AU - Yuankun Zhu
AU - Giacomo B. Marino
AU - Xiaoyu Song
AU - Simona Migliozzi
AU - Jeffrey R. Whiteaker
AU - Dmitry Rykunov
AU - Yingwei Hu
AU - Noshad Hosseini
AU - Jo Lynne Rokita
AU - Felipe da Veiga Leprevost
AU - Komal S. Rathi
AU - Lijun Chen
AU - Yi-Ting Wang
AU - Karl K. Weitz
AU - Rosalie K. Chu
AU - Ronald J. Moore
AU - Azra Krek
AU - Weijia Fu
AU - Xuran Wang
AU - Eden Z. Deng
AU - Chia-Feng Tsai
AU - Tyler Sagendorf
AU - Vladislav A. Petyuk
AU - Tujin Shi
AU - Thomas L. Fillmore
AU - Rui Zhao
AU - Matthew E. Monroe
AU - Marius V. Dannappel
AU - Paul Daniel
AU - Lei Zhao
AU - Richard G. Ivey
AU - Uliana J. Voytovich
AU - Tomer M. Yaron-Barir
AU - Emily M. Huntsman
AU - Jared L. Johnson
AU - Nakib Abedin
AU - Yan-chak Li
AU - Mariarita Santi
AU - Demetri Dupal
AU - Jena Lilly
AU - Adam Kraya
AU - Joseph M. Dybas
AU - Bo Zhang
AU - Chuwei Zhong
AU - Miguel A. Brown
AU - Saksham Phul
AU - Eric Wafula
AU - Alvin Farrel
AU - Zhuangzhuang Geng
AU - Ryan J. Corbett
AU - Ammar S. Naqvi
AU - Daniel P. Miller
AU - Jennifer Mason
AU - Tatiana S. Patton
PY - 2026
DA - 2026/09/17
JO - Cell Reports Medicine
DO - 10.1016/j.xcrm.2026.103024
UR - https://doi.org/10.1016/j.xcrm.2026.103024
AB - 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.
SN - 2666-3791
ER -