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Cited by 661Glioma Diagnosis and TreatmentCancer Genomics and DiagnosticsCancer, Hypoxia, and Metabolism

The DOI matches its Crossref record; 150 of the 153 references it cites were found in a registry or an index.

Proteogenomic and metabolomic characterization of human glioblastoma

Open access
Wang, Liang-Bo, Karpova, Alla, Gritsenko, Marina A., 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, Olsen, Lindsey K., Liang, Wen-Wei, Song, Xiaoyu, Dou, Yongchao, Wendl, Michael C., Caravan, Wagma, Liu, Wenke, Cui Zhou, Daniel, 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, Demopoulos, Alexis, Zhu, Houxiang, Wyczalkowski, Matthew A., McMichael, Joshua F., Henderson, Brittany L., Lindgren, Caleb M., Boekweg, Hannah, Lu, Shuangjia, Baral, Jessika, Yao, Lijun, 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, Chen, Xi S., Cottingham, Sandra L., Li, Qing Kay, Kim, Albert H., Fenyö, David, Ruggles, Kelly V., Rodriguez, Henry, Mesri, Mehdi, Payne, Samuel H., Resnick, Adam C., Wang, Pei, Smith, Richard D., Iavarone, Antonio, Chheda, Milan G., Barnholtz-Sloan, Jill S., Rodland, Karin D., Liu, Tao, Ding, Li, Agarwal, Anupriya, Amin, Mitual, An, Eunkyung, Anderson, Matthew L., Andrews, David W., Bauer, Thomas, Birger, Chet, Birrer, Michael J., Blumenberg, Lili, Bocik, William E., Borate, Uma, Borucki, Melissa, Burke, Meghan C., Cai, Shuang, Calinawan, Anna P., Carr, Steven A., Cerda, Sandra, Chan, Daniel W., Charamut, Alyssa, Chen, Lin S., Chesla, David, Chinnaiyan, Arul M., Chowdhury, Shrabanti, Cieślik, Marcin P., Clark, David J., Culpepper, Houston, Czernicki, Tomasz, D'Angelo, Fulvio, Day, Jacob, De Young, Stephanie, Demir, Emek, Dhanasekaran, Saravana Mohan, Dhir, Rajiv, Domagalski, Marcin J., Druker, Brian, Duffy, Elizabeth, Dyer, Maureen, Edwards, Nathan J., Edwards, Robert, Elburn, Kimberly, Ellis, Matthew J., Eschbacher, Jennifer, Francis, Alicia, Gabriel, Stacey, Gabrovski, Nikolay, Garofano, Luciano, Getz, Gad, Gillette, Michael A., Godwin, Andrew K., Golbin, Denis, Hanhan, Ziad, Hannick, Linda I., Hariharan, Pushpa, Hindenach, Barbara, Hoadley, Katherine A., Hostetter, Galen, Huang, Chen, Jaehnig, Eric, Jewell, Scott D., Ji, Nan, Jones, Corbin D., Karz, Alcida, Kaspera, Wojciech, Kim, Lyndon, Kothadia, Ramani B., Kumar-Sinha, Chandan, Lei, Jonathan, Leprevost, Felipe D., Li, Kai, Liao, Yuxing, Lilly, Jena, Liu, Hongwei, Lubínski, Jan, Madan, Rashna, Maggio, William, Malc, Ewa, Malovannaya, Anna, Mareedu, Sailaja, Markey, Sanford P., Marrero-Oliveras, Annette, Martinez, Nina, Maunganidze, Nicollette, McDermott, Jason E., McGarvey, Peter B., McGee, John, Mieczkowski, Piotr, Migliozzi, Simona, Modugno, Francesmary, Montgomery, Rebecca, Newton, Chelsea J., Omenn, Gilbert S., Ozbek, Umut, Paklina, Oxana V., Paulovich, Amanda G., Perou, Amy M., Pico, Alexander R., Piehowski, Paul D., Placantonakis, Dimitris G., Polonskaya, Larisa, Potapova, Olga, Pruetz, Barbara, Qi, Liqun, Ramkissoon, Shakti, Resnick, Adam, Richey, Shannon, Riggins, Gregory, Robinson, Karna, Roche, Nancy, Rohrer, Daniel C., Rood, Brian R., Rossell, Larissa, Savage, Sara R., Schadt, Eric E., Shi, Yan, Shi, Zhiao, Shutack, Yvonne, Singh, Shilpi, Skelly, Tara, Sokoll, Lori J., Stawicki, Jakub, Stein, Stephen E., Suh, James, Szopa, Wojciech, Tabor, Dave, Tan, Donghui, Tansil, Darlene, Thangudu, Ratna R., Tognon, Cristina, Traer, Elie, Tsang, Shirley, Tyner, Jeffrey, Um, Ki Sung, Valley, Dana R., Vasaikar, Suhas, Vatanian, Negin, Velvulou, Uma, Vernon, Michael, Wan, Weiqing, Wang, Junmei, Webster, Alex, Wen, Bo, Whiteaker, Jeffrey R., Wilson, George D., Zakhartsev, Yuriy, Zelt, Robert, Zhang, Hui, Zhang, Liwei, Zhang, Zhen, Zhao, Grace, Zhu, Jun·2021·Cancer Cell
DOI 10.1016/j.ccell.2021.01.006PMC PMC8044053
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Abstract

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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  1. Pilarczyk, 2019, Connecting Omics Signatures of Diseases, Drugs, and Mechanisms of Actions with iLINCS, BioRxiv, 826271

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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
Venue
Cancer Cell
Publisher
Elsevier BV
Published
2021-04
Volume
39
Issue
4
Pages
509-528.e20
ISSN
1535-6108 (ISSN-L)
DOI
10.1016/j.ccell.2021.01.006
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
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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