Proteogenomic Characterization of Endometrial Carcinoma
Yongchao Dou, Emily Kawaler, Daniel Cui Zhou, Marina A. Gritsenko, Chen Huang, Lili M. Blumenberg, Alla Y. Karpova, Vladislav Petyuk, Sara R. Savage, Shankha Satpathy, Wenke Liu, Yige Wu, Chia‐Feng Tsai, Bo Wen, Zhi Li, Song Cao, Jamie Moon, Zhiao Shi, MacIntosh Cornwell, Matthew A. Wyczalkowski, Rosalie Chu, Suhas Vasaikar, Hua Zhou, Qingsong Gao, Ronald Moore, Kai Li, Sunantha Sethuraman, Matthew Monroe, Rui Zhao, David I. Heiman, Karsten Krug, Karl R. Clauser, Ramani Kothadia, Yosef E. Maruvka, Alexander R. Pico, Amanda E. Oliphant, Emily L. Hoskins, Samuel L. Pugh, Sean J.I. Beecroft, David W. Adams, Jonathan C. Jarman, Andy T. Kong, Hui-Yin Chang, Boris Reva, Yuxing Liao, Dmitry Rykunov, Antonio Colaprico, Xi Chen, Andrzej Czekański, Marcin Jędryka, Rafał Matkowski, Maciej Wiznerowicz, Tara Hiltke, Emily S. Boja, Christopher R. Kinsinger, Mehdi Mesri, Ana I. Robles, Henry Rodriguez, David G. Mutch, Katherine C. Fuh, Matthew J. Ellis, Deborah F. DeLair, Mathangi Thiagarajan, D.R. Mani, Gad Getz, Michael S. Noble, Alexey I. Nesvizhskii, Pei Wang, Matthew L. Anderson, Douglas A. Levine, Richard Smith, Samuel Payne, Kelly V. Ruggles, Karin Rodland, Li Ding, Bing Zhang, Tao Liu, David Fenyö, Anupriya Agarwal, Meenakshi Anurag, Dmitry M. Avtonomov, Chet Birger, Michael J. Birrer, Simina M. Boca, William Bocik, Uma Borate, Melissa Borucki, Meghan C. Burke, Shuang Cai, Anna Calinawan, Steven A. Carr, Sonya Carter, Patricia Castro, Sandra Cerda, Michelle Chaikin, Daniel W. Chan, Doug W. Chan, Alyssa Charamut, Feng Chen, Jin Chen
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.