Proteogenomic and metabolomic characterization of human glioblastoma
Authors: Liang-Bo Wang, Alla Karpova, Marina A. Gritsenko, Jennifer E. 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 A. Petyuk, Jamie Moon, Weiping Ma, Rosalie K. Chu, Karl K. Weitz, Ronald J. Moore, Matthew E. Monroe, Rui Zhao, Xiaolu Yang, Seungyeul Yoo, Azra Krek, Alexis Demopoulos, Houxiang Zhu, Matthew A. Wyczalkowski, Joshua F. McMichael, Brittany L. Henderson, Caleb M. Lindgren, Hannah Boekweg, Shuangjia Lu, Jessika Baral, Lijun Yao, Kelly G. Stratton, Lisa M. Bramer, Erika Zink, Sneha P. Couvillion, Kent J. Bloodsworth, Shankha Satpathy, Weiva Sieh, Simina M. Boca, Stephan 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 L. Cottingham, Qing Kay Li, Albert H. Kim, David Fenyö, Kelly V. Ruggles, Henry Rodriguez, Mehdi Mesri, Samuel H. Payne, Adam C. Resnick, Pei Wang, Richard D. Smith, Antonio Iavarone, Milan G. Chheda, Jill S. Barnholtz-Sloan, Karin D. 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 Blumenberg, William E. Bocik, Uma Borate, Melissa Borucki, Meghan C. Burke, Shuang Cai, Anna P. Calinawan, Steven A. Carr, Sandra Cerda, Daniel W. Chan, Alyssa Charamut, Lin S. Chen, David Chesla, Arul M. Chinnaiyan, Shrabanti Chowdhury, Marcin P. Cieślik, David J. Clark, Houston Culpepper, Tomasz Czernicki, Fulvio D'Angelo, Jacob Day, Stephanie De Young, Emek Demir, Saravana Mohan Dhanasekaran, Rajiv Dhir, Marcin J. Domagalski, Brian Druker, Elizabeth Duffy, Maureen Dyer, Nathan J. Edwards, Robert Edwards, Kimberly Elburn, Matthew J. Ellis, Jennifer Eschbacher, Alicia Francis, Stacey Gabriel, Nikolay Gabrovski, Luciano Garofano, Gad Getz, Michael A. Gillette, Andrew K. Godwin, Denis Golbin, Ziad Hanhan, Linda I. Hannick, Pushpa Hariharan, Barbara Hindenach, Katherine A. Hoadley, Galen Hostetter, Chen Huang, Eric Jaehnig, Scott D. Jewell, Nan Ji, Corbin D. Jones, Alcida Karz, Wojciech Kaspera, Lyndon Kim, Ramani B. Kothadia, Chandan Kumar-Sinha, Jonathan Lei, Felipe D. Leprevost, Kai Li, Yuxing Liao, Jena Lilly, Hongwei Liu, Jan Lubínski, Rashna Madan, William Maggio, Ewa Malc, Anna Malovannaya, Sailaja Mareedu, Sanford P. Markey, Annette Marrero-Oliveras, Nina Martinez, Nicollette Maunganidze, Jason E. McDermott, Peter B. McGarvey, John McGee, Piotr Mieczkowski, Simona Migliozzi, Francesmary Modugno, Rebecca Montgomery, Chelsea J. Newton, Gilbert S. Omenn, Umut Ozbek, Oxana V. Paklina, Amanda G. Paulovich, Amy M. Perou, Alexander R. Pico, Paul D. Piehowski, Dimitris G. Placantonakis, Larisa Polonskaya, Olga Potapova, Barbara Pruetz, Liqun Qi, Shakti Ramkissoon, Adam Resnick, Shannon Richey, Gregory Riggins, Karna Robinson, Nancy Roche, Daniel C. Rohrer, Brian R. Rood, Larissa 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 Tognon, Elie Traer, Shirley Tsang, Jeffrey Tyner, Ki Sung Um, Dana R. Valley, Suhas Vasaikar, Negin Vatanian, Uma Velvulou, Michael 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
Journal: Cancer Cell (2021)

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.