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Proteogenomic and metabolomic characterization of human glioblastoma

2021; Cell Press; Volume: 39; Issue: 4 Linguagem: Inglês

10.1016/j.ccell.2021.01.006

1878-3686

Liang-Bo Wang, Alla Karpova, Marina Gritsenko, Jennifer Kyle, Song Cao, Yize Li, Dmitry Rykunov, Antonio Colaprico, Joseph H. Rothstein, Runyu Hong, Vasileios Stathias, MacIntosh Cornwell, Francesca Petralia, Yige Wu, Boris Reva, Karsten Krug, Pietro Pugliese, Emily Kawaler, Lindsey K. Olsen, Wen-Wei Liang, Xiaoyu Song, Yongchao Dou, Michael C. Wendl, Wagma Caravan, Wenke Liu, Daniel Cui Zhou, Jiayi Ji, Chia‐Feng Tsai, Vladislav Petyuk, Jamie Moon, Weiping Ma, Rosalie Chu, Karl Weitz, Ronald J. Moore, Matthew Monroe, Rui Zhao, Xiaolu Yang, Seungyeul Yoo, Azra Krek, Alexis Demopoulos, Houxiang Zhu, Matthew A. Wyczalkowski, Joshua F. McMichael, Brittany Henderson, Caleb M. Lindgren, Hannah Boekweg, Shuangjia Lu, Jessika Baral, Lijun Yao, Kelly G. Stratton, Lisa Bramer, Erika Zink, Sneha Couvillion, Kent Bloodsworth, Shankha Satpathy, Weiva Sieh, Simina M. Boca, Stephan C. Schürer, Feng Chen, Maciej Wiznerowicz, Karen A. Ketchum, Emily S. Boja, Christopher R. Kinsinger, Ana I. Robles, Tara Hiltke, Mathangi Thiagarajan, Alexey I. Nesvizhskii, Bing Zhang, D.R. Mani, Michele Ceccarelli, Xi S. Chen, Sandra Cottingham, Qing Kay Li, Albert H. Kim, David Fenyö, Kelly V. Ruggles, Henry Rodriguez, Mehdi Mesri, Samuel Payne, Adam Resnick, Pei Wang, Richard Smith, Antonio Iavarone, Milan G. Chheda, Jill S. Barnholtz‐Sloan, Karin Rodland, Tao Liu, Li Ding, Anupriya Agarwal, Mitual Amin, Eunkyung An, Matthew L. Anderson, David W. Andrews, Thomas Bauer, Chet Birger, Michael J. Birrer, Lili M. Blumenberg, William Bocik, Uma Borate, Melissa Borucki, Meghan C. Burke, Shuang Cai, Anna Calinawan, Steven A. Carr, Sandra Cerda, Daniel W. Chan, Alyssa Charamut, Lin Chen, David Chesla, Arul M. Chinnaiyan, Shrabanti Chowdhury, Marcin Cieślik, David Clark, Houston Culpepper, Tomasz Czernicki, Fulvio D’Angelo, Jacob Day, Stephanie Young, Emek Demir, Saravana M. Dhanasekaran, Rajiv Dhir, Marcin J. Domagalski, Brian J. Druker, Elizabeth R. Duffy, Maureen A. Dyer, Nathan Edwards, Robert A. Edwards, Kimberly Elburn, Matthew J. Ellis, Jennifer Eschbacher, Alicia Francis, Stacey Gabriel, N Gabrovski, Luciano Garofano, Gad Getz, Michael A. Gillette, Andrew K. Godwin, D A Gol'bin, Ziad Hanhan, Linda I. Hannick, Pushpa Hariharan, Barbara Hindenach, Katherine A. Hoadley, Galen Hostetter, Chen Huang, Eric J. Jaehnig, Scott D. Jewell, Nan Ji, Corbin D. Jones, Alcida Karz, Wojciech Kaspera, Lyndon Kim, Ramani Kothadia, Chandan Kumar‐Sinha, Jonathan T. Lei, Felipe da Veiga Leprevost, Kai Li, Yuxing Liao, Jena Lilly, Hongwei Liu, Jan Lubiński, Rashna Madan, William W. Maggio, Ewa P. Malc, Anna Malovannaya, Sailaja Mareedu, Sanford P. Markey, Annette Marrero-Oliveras, Nina Martinez, Nicollette Maunganidze, Jason McDermott, Peter B. McGarvey, John P. McGee, Piotr A. Mieczkowski, Simona Migliozzi, Francesmary Modugno, Rebecca Montgomery, Chelsea J. Newton, Gilbert S. Omenn, Umut Özbek, Oxana Paklina, Amanda G. Paulovich, Amy M. Perou, Alexander R. Pico, Paul Piehowski, Dimitris G. Placantonakis, Larisa Polonskaya, Olga Potapova, Barbara L. Pruetz, Liqun Qi, Shakti Ramkissoon, Adam Resnick, Shannon Richey, Gregory J. Riggins, Karna Robinson, Nancy Roche, Daniel C. Rohrer, Brian R. Rood, Larissa L. Rossell, Sara R. Savage, Eric E. Schadt, Yan Shi, Zhiao Shi, Yvonne Shutack, Shilpi Singh, Tara Skelly, Lori J. Sokoll, Jakub Stawicki, Stephen E. Stein, James Suh, Wojciech Szopa, Dave Tabor, Donghui Tan, Darlene Tansil, Ratna R. Thangudu, Cristina E. Tognon, Elie Traer, Shirley Tsang, Jeffrey W. Tyner, Ki Sung Um, Dana R. Valley, Suhas Vasaikar, Negin Vatanian, Uma Velvulou, Michael W. Vernon, Weiqing Wan, Junmei Wang, Alex Webster, Bo Wen, Jeffrey R. Whiteaker, George D. Wilson, Yuriy Zakhartsev, Robert Zelt, Hui Zhang, Liwei Zhang, Zhen Zhang, Grace Zhao, Jun Zhu,

Immune cells in cancer

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.