Proteogenomic Characterization of Endometrial Carcinoma
Yongchao Dou(Baylor College of Medicine), Emily Kawaler(Institute for Systems Biology), Daniel Cui Zhou(James S. McDonnell Foundation), Marina A. Gritsenko(Pacific Northwest National Laboratory), Chen Huang(Baylor College of Medicine), Lili M. Blumenberg(New York University), Alla Y. Karpova(James S. McDonnell Foundation), Vladislav Petyuk(Pacific Northwest National Laboratory), Sara R. Savage(Baylor College of Medicine), Shankha Satpathy(Broad Institute), Wenke Liu(Institute for Systems Biology), Yige Wu(James S. McDonnell Foundation), Chia‐Feng Tsai(Pacific Northwest National Laboratory), Bo Wen(Baylor College of Medicine), Zhi Li(Institute for Systems Biology), Song Cao(James S. McDonnell Foundation), Jamie Moon(Pacific Northwest National Laboratory), Zhiao Shi(Baylor College of Medicine), MacIntosh Cornwell(Institute for Systems Biology), Matthew A. Wyczalkowski(James S. McDonnell Foundation), Rosalie Chu(Pacific Northwest National Laboratory), Suhas Vasaikar(The University of Texas MD Anderson Cancer Center), Hua Zhou(Institute for Systems Biology), Qingsong Gao(James S. McDonnell Foundation), Ronald Moore(Pacific Northwest National Laboratory), Kai Li(Baylor College of Medicine), Sunantha Sethuraman(James S. McDonnell Foundation), Matthew Monroe(Pacific Northwest National Laboratory), Rui Zhao(Pacific Northwest National Laboratory), David I. Heiman(Broad Institute), Karsten Krug(Broad Institute), Karl R. Clauser(Broad Institute), Ramani Kothadia(Broad Institute), Yosef E. Maruvka(Broad Institute), Alexander R. Pico(Gladstone Institutes), Amanda E. Oliphant(Brigham Young University), Emily L. Hoskins(Brigham Young University), Samuel L. Pugh(Brigham Young University), Sean J.I. Beecroft(Brigham Young University), David W. Adams(Brigham Young University), Jonathan C. Jarman(Brigham Young University), Andy T. Kong(University of Michigan), Hui-Yin Chang(University of Michigan), Boris Reva(Icahn School of Medicine at Mount Sinai), Yuxing Liao(Baylor College of Medicine), Dmitry Rykunov(Icahn School of Medicine at Mount Sinai), Antonio Colaprico(University of Miami), Xi Chen(University of Miami), Andrzej Czekański(Wroclaw Medical University), Marcin Jędryka(Wroclaw Medical University), Rafał Matkowski(Wroclaw Medical University), Maciej Wiznerowicz(Poznan University of Medical Sciences), Tara Hiltke(National Cancer Institute), Emily S. Boja(National Cancer Institute), Christopher R. Kinsinger(National Cancer Institute), Mehdi Mesri(National Cancer Institute), Ana I. Robles(National Cancer Institute), Henry Rodriguez(National Cancer Institute), David G. Mutch(Washington University in St. Louis), Katherine C. Fuh(Washington University in St. Louis), Matthew J. Ellis(Baylor College of Medicine), Deborah F. DeLair(NYU Langone Health), Mathangi Thiagarajan(Leidos (United States)), D.R. Mani(Broad Institute), Gad Getz(Broad Institute), Michael S. Noble(Broad Institute), Alexey I. Nesvizhskii(University of Michigan), Pei Wang(Icahn School of Medicine at Mount Sinai), Matthew L. Anderson(University of South Florida), Douglas A. Levine(Gynecologic Oncology Group), Richard Smith(Pacific Northwest National Laboratory), Samuel Payne(Brigham Young University), Kelly V. Ruggles(New York University), Karin Rodland(Pacific Northwest National Laboratory), Li Ding(James S. McDonnell Foundation), Bing Zhang(Baylor College of Medicine), Tao Liu(Pacific Northwest National Laboratory), David Fenyö(Institute for Systems Biology), Anupriya Agarwal, Meenakshi Anurag, Dmitry M. Avtonomov(Icahn School of Medicine at Mount Sinai), Chet Birger, Michael J. Birrer, Simina M. Boca, William Bocik, Uma Borate, Melissa Borucki, Meghan C. Burke, Shuang Cai, Anna Calinawan, Steven A. Carr(University of Miami), Sonya Carter, Patricia Castro, Sandra Cerda, Michelle Chaikin, Daniel W. Chan(University of Michigan), Doug W. Chan(University of Michigan), Alyssa Charamut, Feng Chen(University of Miami), Jin Chen(University of Miami), Lijun Chen(University of Miami), Lin S. Chen(University of Miami), David Chesla(Institute for Systems Biology), Milan G. Chheda, Arul M. Chinnaiyan, Shrabanti Chowdhury, Marcin Cieślik, David Clark, Sandra Cottingham, Houston Culpepper, Jacob Day, Stephanie Young, Emek Demir, Saravana M. Dhanasekaran, Rajiv Dhir, Marcin J. Domagalski(Wroclaw Medical University), Peter R. Dottino, Brian Druker, Elizabeth R. Duffy, Maureen A. Dyer, Nathan Edwards, Robert A. Edwards, Kim Elburn, Jayson B. Field, Alicia Francis, Stacey Gabriel, Yifat Geffen, Daniel Geiszler(James S. McDonnell Foundation), Michael A. Gillette(Broad Institute), Andrew K. Godwin, Pamela Grady, Linda I. Hannick, Pushpa Hariharan, S. G. Hilsenbeck, Barbara Hindenach, Katherine A. Hoadley(Washington University in St. Louis), Runyu Hong, Galen Hostetter, James J. Hsieh, Yingwei Hu(University of Michigan), Michael Ittmann, Eric J. Jaehnig, Scott D. Jewell, Jiayi Ji(Brigham Young University), Corbin D. Jones, Renee Karabon, Karen A. Ketchum, Munziba Khan, Beom‐Jun Kim, Azra Krek, Tanya Krubit, Chandan Kumar‐Sinha, Felipe da Veiga Leprevost, Michael R. Lewis(Broad Institute), Qing Kay Li, Yize Li, Hongwei Liu(Pacific Northwest National Laboratory), Jan Lubiński(Leidos (United States)), Weiping Ma(University of South Florida), Rashna Madan, Ewa P. Malc, Anna Malovannaya, Sailaja Mareedu, Sanford P. Markey, Annette Marrero-Oliveras, John A. Martignetti, Jason McDermott, Peter B. McGarvey, John P. McGee, Piotr A. Mieczkowski, Francesmary Modugno, Rebecca Montgomery, Chelsea J. Newton, Gilbert S. Omenn, Amanda G. Paulovich, Amy M. Perou, Francesca Petralia, Paul Piehowski, Larisa Polonskaya, Liqun Qi(James S. McDonnell Foundation), Shannon Richey, Karna Robinson, Nancy Roche, Daniel C. Rohrer(James S. McDonnell Foundation), Eric E. Schadt, Michael Schnaubelt(Broad Institute), Yan Shi(Baylor College of Medicine), Tara Skelly(National Cancer Institute), Lori J. Sokoll, Xiaoyu Song(James S. McDonnell Foundation), Stephen E. Stein, James Suh(The University of Texas MD Anderson Cancer Center), Donghui Tan, Darlene Tansil, Guo Ci Teo, Ratna R. Thangudu, Cristina E. Tognon, Elie Traer, Jeffrey Tyner, Ki Sung Um, Dana R. Valley, Negin Vatanian, Pankaj Vats, Uma Velvulou, Michael W. Vernon(Broad Institute), Liang-Bo Wang(Icahn School of Medicine at Mount Sinai), Ying Wang(Icahn School of Medicine at Mount Sinai), Alex Webster(University of Michigan), Thomas F. Westbrook, David A. Wheeler(Institute for Systems Biology), Jeffrey R. Whiteaker, George D. Wilson, Yuriy Zakhartsev, Robert Zelt, Hui Zhang(Baylor College of Medicine), Yuping Zhang(Baylor College of Medicine), Zhen Zhang(Baylor College of Medicine), Grace Zhao(Pacific Northwest National Laboratory)
Cited by 530Open Access
Abstract
We undertook a comprehensive proteogenomic characterization of 95 prospectively collected endometrial carcinomas, comprising 83 endometrioid and 12 serous tumors. This analysis revealed possible new consequences of perturbations to the p53 and Wnt/β-catenin pathways, identified a potential role for circRNAs in the epithelial-mesenchymal transition, and provided new information about proteomic markers of clinical and genomic tumor subgroups, including relationships to known druggable pathways. An extensive genome-wide acetylation survey yielded insights into regulatory mechanisms linking Wnt signaling and histone acetylation. We also characterized aspects of the tumor immune landscape, including immunogenic alterations, neoantigens, common cancer/testis antigens, and the immune microenvironment, all of which can inform immunotherapy decisions. Collectively, our multi-omic analyses provide a valuable resource for researchers and clinicians, identify new molecular associations of potential mechanistic significance in the development of endometrial cancers, and suggest novel approaches for identifying potential therapeutic targets.
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