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Proteogenomic and metabolomic characterization of human glioblastoma
Open accessAbstract
Glioblastoma (GBM) is the most aggressive nervous system cancer. Understanding its molecular pathogenesis is crucial to improving diagnosis and treatment. Integrated analysis of genomic, proteomic, post-translational modification and metabolomic data on 99 treatment-naive GBMs provides insights to GBM biology. We identify key phosphorylation events (e.g., phosphorylated PTPN11 and PLCG1) as potential switches mediating oncogenic pathway activation, as well as potential targets for EGFR-, TP53-, and RB1-altered tumors. Immune subtypes with distinct immune cell types are discovered using bulk omics methodologies, validated by snRNA-seq, and correlated with specific expression and histone acetylation patterns. Histone H2B acetylation in classical-like and immune-low GBM is driven largely by BRDs, CREBBP, and EP300. Integrated metabolomic and proteomic data identify specific lipid distributions across subtypes and distinct global metabolic changes in IDH-mutated tumors. This work highlights biological relationships that could contribute to stratification of GBM patients for more effective treatment.
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“High-throughput genomic, epigenomic, and transcriptomic profiling of glioblastoma cells revealed three main subtypes harboring distinct molecular and phenotypic landscapes that affect response to the therapy and clinical outcome: mesenchymal, proneural, and classical subtypes.96,97,98,99,100”
From MiR-128-3p – a gray eminence of the human central nervous system (2024) · cites this paper as [100]
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Research works printed but not linked: 1
- Pilarczyk, 2019, Connecting Omics Signatures of Diseases, Drugs, and Mechanisms of Actions with iLINCS, BioRxiv, 826271
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Metadata
- Authors
- Wang, L.-B., Karpova, A., Gritsenko, M. A., Kyle, J. E., Cao, S., Li, Y., Rykunov, D., Colaprico, A., Rothstein, J. H., Hong, R., Stathias, V., Cornwell, M., Petralia, F., Wu, Y., Reva, B., Krug, K., Pugliese, P., Kawaler, E., Olsen, L. K., Liang, W.-W., Song, X., Dou, Y., Wendl, M. C., Caravan, W., Liu, W., Cui Zhou, D., Ji, J., Tsai, C.-F., Petyuk, V. A., Moon, J., Ma, W., Chu, R. K., Weitz, K. K., Moore, R. J., Monroe, M. E., Zhao, R., Yang, X., Yoo, S., Krek, A., Demopoulos, A., Zhu, H., Wyczalkowski, M. A., McMichael, J. F., Henderson, B. L., Lindgren, C. M., Boekweg, H., Lu, S., Baral, J., Yao, L., Stratton, K. G., Bramer, L. M., Zink, E., Couvillion, S. P., Bloodsworth, K. J., Satpathy, S., Sieh, W., Boca, S. M., Schürer, S., Chen, F., Wiznerowicz, M., Ketchum, K. A., Boja, E. S., Kinsinger, C. R., Robles, A. I., Hiltke, T., Thiagarajan, M., Nesvizhskii, A. I., Zhang, B., Mani, D. R., Ceccarelli, M., Chen, X. S., Cottingham, S. L., Li, Q. K., Kim, A. H., Fenyö, D., Ruggles, K. V., Rodriguez, H., Mesri, M., Payne, S. H., Resnick, A. C., Wang, P., Smith, R. D., Iavarone, A., Chheda, M. G., Barnholtz-Sloan, J. S., Rodland, K. D., Liu, T., Ding, L., Agarwal, A., Amin, M., An, E., Anderson, M. L., Andrews, D. W., Bauer, T., Birger, C., Birrer, M. J., Blumenberg, L., Bocik, W. E., Borate, U., Borucki, M., Burke, M. C., Cai, S., Calinawan, A. P., Carr, S. A., Cerda, S., Chan, D. W., Charamut, A., Chen, L. S., Chesla, D., Chinnaiyan, A. M., Chowdhury, S., Cieślik, M. P., Clark, D. J., Culpepper, H., Czernicki, T., D'Angelo, F., Day, J., De Young, S., Demir, E., Dhanasekaran, S. M., Dhir, R., Domagalski, M. J., Druker, B., Duffy, E., Dyer, M., Edwards, N. J., Edwards, R., Elburn, K., Ellis, M. J., Eschbacher, J., Francis, A., Gabriel, S., Gabrovski, N., Garofano, L., Getz, G., Gillette, M. A., Godwin, A. K., Golbin, D., Hanhan, Z., Hannick, L. I., Hariharan, P., Hindenach, B., Hoadley, K. A., Hostetter, G., Huang, C., Jaehnig, E., Jewell, S. D., Ji, N., Jones, C. D., Karz, A., Kaspera, W., Kim, L., Kothadia, R. B., Kumar-Sinha, C., Lei, J., Leprevost, F. D., Li, K., Liao, Y., Lilly, J., Liu, H., Lubínski, J., Madan, R., Maggio, W., Malc, E., Malovannaya, A., Mareedu, S., Markey, S. P., Marrero-Oliveras, A., Martinez, N., Maunganidze, N., McDermott, J. E., McGarvey, P. B., McGee, J., Mieczkowski, P., Migliozzi, S., Modugno, F., Montgomery, R., Newton, C. J., Omenn, G. S., Ozbek, U., Paklina, O. V., Paulovich, A. G., Perou, A. M., Pico, A. R., Piehowski, P. D., Placantonakis, D. G., Polonskaya, L., Potapova, O., Pruetz, B., Qi, L., Ramkissoon, S., Resnick, A., Richey, S., Riggins, G., Robinson, K., Roche, N., Rohrer, D. C., Rood, B. R., Rossell, L., Savage, S. R., Schadt, E. E., Shi, Y., Shi, Z., Shutack, Y., Singh, S., Skelly, T., Sokoll, L. J., Stawicki, J., Stein, S. E., Suh, J., Szopa, W., Tabor, D., Tan, D., Tansil, D., Thangudu, R. R., Tognon, C., Traer, E., Tsang, S., Tyner, J., Um, K. S., Valley, D. R., Vasaikar, S., Vatanian, N., Velvulou, U., Vernon, M., Wan, W., Wang, J., Webster, A., Wen, B., Whiteaker, J. R., Wilson, G. D., Zakhartsev, Y., Zelt, R., Zhang, H., Zhang, L., Zhang, Z., Zhao, G., & Zhu, J.
- Affiliations
- Washington University in St. Louis (US)
- Pacific Northwest National Laboratory (US)
- Icahn School of Medicine at Mount Sinai (US)
- University of Miami (US)
- NYU Langone Health (US)
- New York University (US)
- Broad Institute (US)
- University of Sannio (IT)
- Brigham Young University (US)
- Tisch Cancer Institute (US)
- Baylor College of Medicine (US)
- Poznan University of Medical Sciences (PL)
- Northwell Health (US)
- Georgetown University Medical Center (US)
- Enterprise Science and Computing (United States) (US)
- National Cancer Institute (US)
- Frederick National Laboratory for Cancer Research (US)
- University of Michigan (US)
- Biogem (IT)
- Spectrum Health (US)
- Johns Hopkins University (US)
- Columbia University Irving Medical Center (US)
- University Hospitals of Cleveland (US)
- Corresponding author
- Rodland, Karin D.
- Liu, Tao
- Ding, Li
- ORCID
- Wang, Liang-Bo
- Karpova, Alla
- Kyle, Jennifer E.
- Cao, Song
- Li, Yize
- Rykunov, Dmitry
- Colaprico, Antonio
- Rothstein, Joseph H.
- Hong, Runyu
- Stathias, Vasileios
- Cornwell, MacIntosh
- Petralia, Francesca
- Wu, Yige
- Reva, Boris
- Krug, Karsten
- Pugliese, Pietro
- Kawaler, Emily
- Liang, Wen-Wei
- Song, Xiaoyu
- Dou, Yongchao
- Wendl, Michael C.
- Caravan, Wagma
- Liu, Wenke
- Ji, Jiayi
- Tsai, Chia-Feng
- Petyuk, Vladislav A.
- Moon, Jamie
- Ma, Weiping
- Chu, Rosalie K.
- Weitz, Karl K.
- Moore, Ronald J.
- Monroe, Matthew E.
- Zhao, Rui
- Yang, Xiaolu
- Yoo, Seungyeul
- Krek, Azra
- Wyczalkowski, Matthew A.
- McMichael, Joshua F.
- Henderson, Brittany L.
- Lindgren, Caleb M.
- Lu, Shuangjia
- Stratton, Kelly G.
- Bramer, Lisa M.
- Zink, Erika
- Couvillion, Sneha P.
- Bloodsworth, Kent J.
- Satpathy, Shankha
- Sieh, Weiva
- Boca, Simina M.
- Schürer, Stephan
- Chen, Feng
- Wiznerowicz, Maciej
- Ketchum, Karen A.
- Boja, Emily S.
- Kinsinger, Christopher R.
- Robles, Ana I.
- Hiltke, Tara
- Thiagarajan, Mathangi
- Nesvizhskii, Alexey I.
- Zhang, Bing
- Mani, D.R.
- Ceccarelli, Michele
- Li, Qing Kay
- Kim, Albert H.
- Fenyö, David
- Ruggles, Kelly V.
- Rodriguez, Henry
- Mesri, Mehdi
- Wang, Pei
- Smith, Richard D.
- Iavarone, Antonio
- Chheda, Milan G.
- Rodland, Karin D.
- Liu, Tao
- Ding, Li
- Agarwal, Anupriya
- Amin, Mitual
- An, Eunkyung
- Anderson, Matthew L.
- Andrews, David W.
- Birrer, Michael J.
- Blumenberg, Lili
- Bocik, William E.
- Borate, Uma
- Burke, Meghan C.
- Cai, Shuang
- Calinawan, Anna P.
- Carr, Steven A.
- Chan, Daniel W.
- Chen, Lin S.
- Chinnaiyan, Arul M.
- Chowdhury, Shrabanti
- Clark, David J.
- Czernicki, Tomasz
- Demir, Emek
- Dhanasekaran, Saravana Mohan
- Dhir, Rajiv
- Domagalski, Marcin J.
- Druker, Brian
- Duffy, Elizabeth
- Dyer, Maureen
- Edwards, Nathan J.
- Edwards, Robert
- Ellis, Matthew J.
- Eschbacher, Jennifer
- Francis, Alicia
- Gabriel, Stacey
- Garofano, Luciano
- Getz, Gad
- Gillette, Michael A.
- Godwin, Andrew K.
- Golbin, Denis
- Hannick, Linda I.
- Hoadley, Katherine A.
- Hostetter, Galen
- Huang, Chen
- Jaehnig, Eric
- Jewell, Scott D.
- Ji, Nan
- Jones, Corbin D.
- Karz, Alcida
- Kaspera, Wojciech
- Kothadia, Ramani B.
- Lei, Jonathan
- Leprevost, Felipe D.
- Li, Kai
- Liao, Yuxing
- Lilly, Jena
- Liu, Hongwei
- Madan, Rashna
- Malc, Ewa
- Malovannaya, Anna
- Martinez, Nina
- McGarvey, Peter B.
- Mieczkowski, Piotr
- Migliozzi, Simona
- Modugno, Francesmary
- Omenn, Gilbert S.
- Paklina, Oxana V.
- Paulovich, Amanda G.
- Pico, Alexander R.
- Piehowski, Paul D.
- Placantonakis, Dimitris G.
- Potapova, Olga
- Riggins, Gregory
- Rohrer, Daniel C.
- Rood, Brian R.
- Savage, Sara R.
- Schadt, Eric E.
- Shi, Yan
- Shi, Zhiao
- Sokoll, Lori J.
- Stawicki, Jakub
- Stein, Stephen E.
- Suh, James
- Szopa, Wojciech
- Thangudu, Ratna R.
- Tognon, Cristina
- Traer, Elie
- Tyner, Jeffrey
- Vasaikar, Suhas
- Wan, Weiqing
- Wen, Bo
- Whiteaker, Jeffrey R.
- Wilson, George D.
- Zhang, Hui
- Zhang, Zhen
- Zhao, Grace
- Zhu, Jun
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2021-04
- Volume
- 39
- Issue
- 4
- Pages
- 509-528.e20
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC8044053
- OpenAlex
- W3126609356
- Cited by
- 661
- References
- 153
- Citations by year
- 2026: 103 · 2025: 124 · 2024: 127 · 2023: 140 · 2022: 123 · 2021: 43
- FWCI
- 62.35
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons-TMC (Texas Medical Center) (submittedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Funders
- National Institutes of Health
- U.S. Department of Energy (DE-AC05-76RL01830)
- National Human Genome Research Institute (R01HG009711, R01NS107833)
- National Cancer Institute (U01CA214125, U24CA210954, U24CA210955, U24CA210967, U24CA210972, U24CA210979, U24CA210985, U24CA210986, U24CA210993)
- Orbus Therapeutics
- Topics
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- glioblastoma, proteogenomics, metabolomics, post-translational modification, protein phosphorylation, PTPN11, phospholipase C-gamma1, EGFR, TP53, RB1, tumor immune subtypes, single-cell RNA sequencing, histone acetylation, CREB-binding protein, EP300, lipid metabolism, IDH mutation, molecular subtypes, patient stratification
- MeSH terms
- Proteogenomics, Brain Neoplasms, Glioblastoma, Humans, Mutation, Phosphorylation, Computational Biology, Proteomics, Phospholipase C gamma, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Metabolomics
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