Multi-scale signaling and tumor evolution in high-grade gliomas
Jingxian Liu(James S. McDonnell Foundation), Song Cao(James S. McDonnell Foundation), Kathleen J. Imbach(Universitat Autònoma de Barcelona), Marina A. Gritsenko(Pacific Northwest National Laboratory), T. Mamie Lih(Johns Hopkins University), Jennifer Kyle(Pacific Northwest National Laboratory), Tomer M. Yaron-Barir(Cornell University), Zev A. Binder(University of Pennsylvania), Yize Li(James S. McDonnell Foundation), Ilya Strunilin(James S. McDonnell Foundation), Yi-Ting Wang(Pacific Northwest National Laboratory), Chia‐Feng Tsai(Pacific Northwest National Laboratory), Weiping Ma(Icahn School of Medicine at Mount Sinai), Lijun Chen(Johns Hopkins University), Natalie M. Clark(Broad Institute), Andrew Shinkle(James S. McDonnell Foundation), Nataly Naser Al Deen(James S. McDonnell Foundation), Wagma Caravan(James S. McDonnell Foundation), Andrew Houston(James S. McDonnell Foundation), Faria Anjum Simin(James S. McDonnell Foundation), Matthew A. Wyczalkowski(James S. McDonnell Foundation), Liang-Bo Wang(James S. McDonnell Foundation), Erik Storrs(James S. McDonnell Foundation), Siqi Chen(James S. McDonnell Foundation), Ritvik Illindala(Washington University in St. Louis), Yuping D. Li(Washington University in St. Louis), Reyka G. Jayasinghe(James S. McDonnell Foundation), Dmitry Rykunov(Icahn School of Medicine at Mount Sinai), Sandra Cottingham(Spectrum Health), Rosalie Chu(Pacific Northwest National Laboratory), Karl Weitz(Pacific Northwest National Laboratory), Ronald Moore(Pacific Northwest National Laboratory), Tyler J. Sagendorf(Pacific Northwest National Laboratory), Vladislav Petyuk(Pacific Northwest National Laboratory), Michael Nestor(Pacific Northwest National Laboratory), Lisa Bramer(Pacific Northwest National Laboratory), Kelly G. Stratton(Pacific Northwest National Laboratory), Athena Schepmoes(Pacific Northwest National Laboratory), Sneha Couvillion(Pacific Northwest National Laboratory), Josie Eder(Pacific Northwest National Laboratory), Young‐Mo Kim(Pacific Northwest National Laboratory), Yuqian Gao(Pacific Northwest National Laboratory), Thomas Fillmore(Spectrum Health), Rui Zhao(Pacific Northwest National Laboratory), Matthew Monroe(Pacific Northwest National Laboratory), Austin N. Southard-Smith(James S. McDonnell Foundation), Yang Eric Li(Washington University in St. Louis), Rita Jui-Hsien Lu(James S. McDonnell Foundation), Jared L. Johnson(Cornell University), Maciej Wiznerowicz(Poznan University of Medical Sciences), Galen Hostetter(Van Andel Institute), Chelsea J. Newton(Van Andel Institute), Karen A. Ketchum(ICF International (United States)), Ratna R. Thangudu(ICF International (United States)), Jill S. Barnholtz‐Sloan(National Cancer Institute), Pei Wang(Icahn School of Medicine at Mount Sinai), David Fenyö(Institute for Systems Biology), Eunkyung An(Cancer Clinic), Mathangi Thiagarajan(Frederick National Laboratory for Cancer Research), Ana I. Robles(Cancer Clinic), D.R. Mani(Broad Institute), Richard D. Smith(Pacific Northwest National Laboratory), Eduard Porta‐Pardo(Josep Carreras Leukaemia Research Institute), Lewis C. Cantley(Harvard University), Antonio Iavarone(University of Miami), Feng Chen(Washington University in St. Louis), Mehdi Mesri(Cancer Clinic), MacLean P. Nasrallah(University of Pennsylvania), Hui Zhang(Johns Hopkins University), Adam Resnick(Children's Hospital of Philadelphia), Milan G. Chheda(Washington University in St. Louis), Karin Rodland(Oregon Health & Science University), Tao Liu(Pacific Northwest National Laboratory), Li Ding(James S. McDonnell Foundation), Anupriya Agarwal, Iyad Alnahhas, Mitual Amin, Eunkyung An(Cancer Clinic), Matthew L. Anderson, David W. Andrews, Meenakshi Anurag, Jill S. Barnholtz-Sloan(National Cancer Institute), Thomas Bauer, Jasmin Bavarva, Zev A. Binder(University of Pennsylvania), Michael J. Birrer, Uma Borate, Melissa Borucki, Lisa M. Bramer(Pacific Northwest National Laboratory), Steven Brem, Shuang Cai, Lewis C. Cantley(Cornell University), Song Cao(Washington University in St. Louis), Wagma Caravan(Washington University in St. Louis), Steven A Carr, Daniel W. Chan, Lijun Chen(Johns Hopkins University), Lin S. Chen(Johns Hopkins University), Xi S. Chen, David Chesla, Milan G. Chheda(Washington University in St. Louis), Arul M. Chinnaiyan, Shrabanti Chowdhury, Rosalie K. Chu(Pacific Northwest National Laboratory), Marcin P. Cieślik, Natalie M. Clark(Broad Institute), Karl Clauser, Antonio Colaprico, Sandra L. Cottingham(Spectrum Health), Sneha P. Couvillion(Pacific Northwest National Laboratory), Reese Crispen, Tomasz Czernicki, Fulvio D’Angelo, Emek Demir, Saravana Mohan Dhanasekaran, Li Ding(Washington University in St. Louis), Marcin J. Domagalski, Yongchao Dou, Brian Druker, Josie Eder(Pacific Northwest National Laboratory), Nathan J. Edwards, Jennifer Eschbacher, David Fenyő(New York University), Thomas H. Fillmore(Spectrum Health), Nikolay Gabrovski, Yuqian Gao(Pacific Northwest National Laboratory), Luciano Garofano, Yifat Geffen, Gad Getz, Michael A. Gillette, Denis Golbin, Charles A. Goldthwaite, Marina A. Gritsenko(Pacific Northwest National Laboratory), Zeynep Gumus, Ziad Hanhan, Beth Hermes, Tara Hiltke, Galen Hostetter(Van Andel Institute), Andrew Houston(Washington University in St. Louis), Chen Huang, Antonio Iavarone(University of Miami), Kathleen J. Imbach(Josep Carreras Leukaemia Research Institute), Eric Jaehnig, Scott D. Jewell, Jared L. Johnson(Cornell University), Kevin D. Judy, Alicia Karz, Wojciech Kaspera, Karen A. Ketchum(ICF International (United States)), Lyndon Kim, Young-Mo Kim(Pacific Northwest National Laboratory), Mateusz P Koptyra, Ramani B Kothadia, Chandan Kumar-Sinha, Jennifer E. Kyle(Pacific Northwest National Laboratory), John Y.K. Lee, Jonathan Lei, Felipe D. Leprevost, Kai Li, Qing Kay Li, Yize Li(Washington University in St. Louis), Zibo Li, Yuxing Liao, Tung-Shing M. Lih(Johns Hopkins University), Jena Lilly, Jingxian Liu(Washington University in St. Louis), Tao Liu(Pacific Northwest National Laboratory), Rita Jui-Hsien Lu(Washington University in St. Louis), Yin Lu, Jan Lubínski, Weiping Ma(Icahn School of Medicine at Mount Sinai), William Maggio, Anna Malovannaya, D.R. Mani(Broad Institute), Nina Martinez, Jason E. McDermott, Peter B. McGarvey, Mehdi Mesri(Cancer Clinic), Simona Migliozzi, Matthew E. Monroe(Pacific Northwest National Laboratory), Ronald J. Moore(Pacific Northwest National Laboratory), Nataly Naser Al Deen(Washington University in St. Louis), MacLean P. Nasrallah(University of Pennsylvania), Michael Nestor(Pacific Northwest National Laboratory), Alexey I. Nesvizhskii, Chelsea J. Newton(Van Andel Institute), Donald M. O’Rourke, Gilbert S. Omenn, Umut Ozbek, Oxana V. Paklina, Amanda G. Paulovich, Samuel H. Payne, Francesca Petralia, Vladislav A. Petyuk(Pacific Northwest National Laboratory), Alexander R. Pico, Paul D. Piehowski, Alexander Pilozzi, Dmitris Placantonakis, Eduard Porta-Pardo(Josep Carreras Leukaemia Research Institute), Olga Potapova, Barbara Pruetz, Adam C. Resnick(Children's Hospital of Philadelphia), Boris Reva, Ana I. Robles(Cancer Clinic), Karin D. Rodland(Oregon Health & Science University), Henry Rodriguez, Daniel C. Rohrer, Brian Rood, Larissa Rossell, Kelly V. Ruggles, Dmitry Rykunov(Icahn School of Medicine at Mount Sinai), Tyler Sagendorf(Pacific Northwest National Laboratory), Atom Sarkar, Shankha Satpathy, Sara R. Savage, Eric E. Schadt, Athena A. Schepmoes(Pacific Northwest National Laboratory), Scott R. Shepard, Zhiao Shi, Yvonne Shutack, Richard D. Smith(Pacific Northwest National Laboratory), Lori J. Sokoll, Yingduo Song, Yizhe Song, Austin N. Southard-Smith(Washington University in St. Louis), Jakub Stawicki, Phillip B. Storm, Kelly G. Stratton(Pacific Northwest National Laboratory), Ilya Strunilin(Washington University in St. Louis), Wojciech Szopa, Ratna R. Thangudu(ICF International (United States)), Mathangi Thiagarajan(Frederick National Laboratory for Cancer Research), Cristina Tognon, Elie Traer, Chia-Feng Tsai(Pacific Northwest National Laboratory), Shirley Tsang, Alan R. Turtz, Jeffrey Tyner, Negin Vatanian, Weiqing Wan, Liang-Bo Wang(Washington University in St. Louis), Pei Wang(Icahn School of Medicine at Mount Sinai), Yi-Ting Wang(Pacific Northwest National Laboratory), Michael W. Weaver, Karl K. Weitz(Pacific Northwest National Laboratory), Bo Wen, Jeffrey R. Whiteaker, Bart Williams, George D. Wilson, Maciej Wiznerowicz(Poznan University of Medical Sciences), Yige Wu, Matthew A. Wyczalkowski(Washington University in St. Louis), Lijun Yao, Tomer M. Yaron, Eric L. Zager, Bing Zhang, Hui Zhang(Johns Hopkins University), Xu Zhang, Zhen Zhang, Rui Zhao(Pacific Northwest National Laboratory), Jun Zhu
Cited by 52Open Access
Abstract
Although genomic anomalies in glioblastoma (GBM) have been well studied for over a decade, its 5-year survival rate remains lower than 5%. We seek to expand the molecular landscape of high-grade glioma, composed of IDH-wildtype GBM and IDH-mutant grade 4 astrocytoma, by integrating proteomic, metabolomic, lipidomic, and post-translational modifications (PTMs) with genomic and transcriptomic measurements to uncover multi-scale regulatory interactions governing tumor development and evolution. Applying 14 proteogenomic and metabolomic platforms to 228 tumors (212 GBM and 16 grade 4 IDH-mutant astrocytoma), including 28 at recurrence, plus 18 normal brain samples and 14 brain metastases as comparators, reveals heterogeneous upstream alterations converging on common downstream events at the proteomic and metabolomic levels and changes in protein-protein interactions and glycosylation site occupancy at recurrence. Recurrent genetic alterations and phosphorylation events on PTPN11 map to important regulatory domains in three dimensions, suggesting a central role for PTPN11 signaling across high-grade gliomas.
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