Proteogenomic Characterization of Endometrial Carcinoma

生物 可药性 Wnt信号通路 免疫系统 表观遗传学 癌症研究 乙酰化 肿瘤微环境 计算生物学 生物信息学 信号转导 免疫学 基因 遗传学
作者
Yongchao Dou,Emily Kawaler,Daniel Cui Zhou,Marina Gritsenko,Chen Huang,Lili M. Blumenberg,Alla Karpova,Vladislav Petyuk,Sara R. Savage,Shankha Satpathy,Wenke Liu,Yige Wu,CF Tsai,Bo Wen,Zhi Li,Song Cao,Jamie Moon,Zhiao Shi,MacIntosh Cornwell,Matthew A. Wyczalkowski,Rosalie K. Chu,Suhas Vasaikar,Hua Zhou,Qingsong Gao,Ronald J. Moore,Kai Li,Sunantha Sethuraman,Matthew Monroe,Rui Zhao,David I. Heiman,Karsten Krug,Karl R. Clauser,Ramani Kothadia,Yosef E. Maruvka,Alexander 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 Steven 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 H. Payne,Kelly V. Ruggles,Karin Rodland,Ding Li,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,Lijun Chen,Lin S. Chen,David Chesla,Milan G. Chheda,Arul M. Chinnaiyan,Shrabanti Chowdhury,Marcin Cieślik,David Clark,Sandra Cottingham,Houston Culpepper,Jacob Day,Singapore Young,Emek Demir,Saravana M. Dhanasekaran,Rajiv Dhir,Marcin J. Domagalski,Peter R. Dottino,Brian J. Druker,Elizabeth Duffy,Maureen A. Dyer,Nathan Edwards,Robert A. Edwards,Kim Elburn,Jayson B. Field,Alicia Francis,Stacey Gabriel,Yifat Geffen,Daniel Geiszler,Michael A. Gillette,Andrew K. Godwin,Pamela Grady,Linda Hannick,Pushpa Hariharan,S. G. Hilsenbeck,Barbara Hindenach,Katherine A. Hoadley,Runyu Hong,Galen Hostetter,James J. Hsieh,Yingwei Hu,Michael Ittmann,Eric J. Jaehnig,Scott D. Jewell,Jiayi Ji,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,Qing Kay Li,Yize Li,Hongwei Liu,Jan Lubiński,Wanli Ma,Rashna Madan,Ewa 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,Shannon Richey,Karna Robinson,Nancy Roche,Daniel C. Rohrer,Eric E. Schadt,Michael Schnaubelt,Yan Shi,Tara Skelly,Lori J. Sokoll,Xiaoyu Song,Stephen E. Stein,James Suh,Donghui Tan,Darlene Tansil,Guo Ci Teo,Ratna R. Thangudu,Cristina E. Tognon,Elie Traer,Jeffrey W. Tyner,Ki Sung Um,Dana R. Valley,Negin Vatanian,Pankaj Vats,Uma Velvulou,Michael Vernon,Liang-Bo Wang,Ying Wang,Alex Webster,Thomas F. Westbrook,David A. Wheeler,Jeffrey R. Whiteaker,George Wilson,Yuriy Zakhartsev,Robert Zelt,Hui Zhang,Yuping Zhang,Zhen Zhang,Grace Zhao
出处
期刊:Cell [Elsevier]
卷期号:180 (4): 729-748.e26 被引量:302
标识
DOI:10.1016/j.cell.2020.01.026
摘要

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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