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Integrated Proteogenomic Characterization across Major Histological Types of Pediatric Brain Cancer

2020; Cell Press; Volume: 183; Issue: 7 Linguagem: Inglês

10.1016/j.cell.2020.10.044

1097-4172

Francesca Petralia, Nicole Tignor, Boris Reva, Mateusz Koptyra, Shrabanti Chowdhury, Dmitry Rykunov, Azra Krek, Weiping Ma, Yuankun Zhu, Jiayi Ji, Anna Calinawan, Jeffrey R. Whiteaker, Antonio Colaprico, Vasileios Stathias, Tatiana Omelchenko, Xiaoyu Song, Pichai Raman, Yiran Guo, Miguel Brown, Richard G. Ivey, John Szpyt, Sanjukta Guha Thakurta, Marina Gritsenko, Karl Weitz, Gonzalo López, Selim Kalaycı, Zeynep H. Gümüş, Seungyeul Yoo, Felipe da Veiga Leprevost, Hui-Yin Chang, Karsten Krug, Lizabeth Katsnelson, Ying Wang, Jacob J. Kennedy, Uliana J. Voytovich, Lei Zhao, Krutika S. Gaonkar, Brian Ennis, Bo Zhang, Valérie Baubet, Lamiya Tauhid, Jena Lilly, Jennifer Mason, Bailey Farrow, Nathan Young, Sarah Leary, Jamie Moon, Vladislav Petyuk, Javad Nazarian, Nithin D. Adappa, James N. Palmer, Robert M. Lober, Samuel Rivero-Hinojosa, Liang-Bo Wang, Joshua M. Wang, Matilda Broberg, Rosalie Chu, Ronald J. Moore, Matthew Monroe, Rui Zhao, Richard Smith, Jun Zhu, Ana I. Robles, Mehdi Mesri, Emily S. Boja, Tara Hiltke, Henry Rodriguez, Bing Zhang, Eric E. Schadt, D.R. Mani, Li Ding, Antonio Iavarone, Maciej Wiznerowicz, Stephan C. Schürer, Xi S. Chen, Allison P. Heath, Jo Lynne Rokita, Alexey I. Nesvizhskii, David Fenyö, Karin Rodland, Tao Liu, Steven P. Gygi, Amanda G. Paulovich, Adam Resnick, Phillip B. Storm, Brian R. Rood, Pei Wang, Alicia Francis, Allison M. Morgan, Angela J. Waanders, Angela N. Viaene, Anna Maria Buccoliero, Arul M. Chinnaiyan, Carina A. Leonard, Cassie Kline, Chiara Caporalini, Christopher R. Kinsinger, Chunde Li, David E. Kram, Derek Hanson, Elizabeth Appert, Emily Kawaler, Eric H. Raabe, Eric M. Jackson, Jeffrey P. Greenfield, Gabrielle S. Stone, Gad Getz, Gerald A. Grant, Guo Ci Teo, Ian F. Pollack, Jason E. Cain, Jessica Foster, Joanna J. Phillips, July E. Palma, Karen A. Ketchum, Kelly V. Ruggles, Lili M. Blumenberg, MacIntosh Cornwell, Mahdi Sarmady, Marcin J. Domagalski, Marcin Cieślik, Mariarita Santi, Marilyn M. Li, Matthew J. Ellis, Matthew A. Wyczalkowski, Meghan Connors, Mirko Scagnet, Nalin Gupta, Nathan Edwards, Nicholas A. Vitanza, Olena M. Vaske, Oren J. Becher, Peter B. McGarvey, Ron Firestein, Sabine Mueller, Samuel G. Winebrake, Saravana M. Dhanasekaran, Shuang Cai, Sonia Partap, Tatiana Patton, Toan Le, Travis D. Lorentzen, Wenke Liu, William Bocik,

Cancer, Hypoxia, and Metabolism

We report a comprehensive proteogenomics analysis, including whole-genome sequencing, RNA sequencing, and proteomics and phosphoproteomics profiling, of 218 tumors across 7 histological types of childhood brain cancer: low-grade glioma (n = 93), ependymoma (32), high-grade glioma (25), medulloblastoma (22), ganglioglioma (18), craniopharyngioma (16), and atypical teratoid rhabdoid tumor (12). Proteomics data identify common biological themes that span histological boundaries, suggesting that treatments used for one histological type may be applied effectively to other tumors sharing similar proteomics features. Immune landscape characterization reveals diverse tumor microenvironments across and within diagnoses. Proteomics data further reveal functional effects of somatic mutations and copy number variations (CNVs) not evident in transcriptomics data. Kinase-substrate association and co-expression network analysis identify important biological mechanisms of tumorigenesis. This is the first large-scale proteogenomics analysis across traditional histological boundaries to uncover foundational pediatric brain tumor biology and inform rational treatment selection.