1. Proteogenomic insights into the biology and treatment of HPV-negative head and neck squamous cell carcinoma
- Author
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Tara Skelly, Wen Jiang, Zhen Zhang, Anupriya Agarwal, Amy M. Perou, Olga Potapova, Christopher R. Kinsinger, Matthew A. Wyczalkowski, David J. Clark, Shuang Cai, Felipe da Veiga Leprevost, Linda Hannick, Chen Huang, Paul D. Piehowski, John McGee, Marcin J. Domagalski, Dmitris Placantonakis, Jianbo Pan, Dana R. Valley, Zhiao Shi, Hui Yin Chang, Karen A. Ketchum, Charles A. Goldthwaite, Małgorzata Wierzbicka, Karsten Krug, Yvonne Shutack, Sara R. Savage, Matthew L. Anderson, Alyssa Charamut, Chandan Kumar-Sinha, Sanford P. Markey, Ratna R. Thangudu, Weiping Ma, Oliver F. Bathe, Antonio Colaprico, Yuxing Liao, Eric E. Schadt, Tomasz Czernicki, Seungyeul Yoo, Xi Chen, Stacey Gabriel, Karl R. Clauser, Daniel C. Rohrer, Uma Borate, Uma Velvulou, Larisa Polonskaya, M. Harry Kane, Dmitry M. Avtonomov, Boris Reva, Jacob J. Day, Barbara Hindenach, Matthew J. Ellis, Katherine A. Hoadley, Emek Demir, Rebecca I. Montgomery, Ewa P. Malc, Fengchao Yu, Lijun Yao, Maciej Wiznerowicz, Annette Marrero-Oliveras, Wojciech Szopa, Sailaja Mareedu, Galen Hostetter, Liqun Qi, Hui Zhang, Yige Wu, David N. Hayes, Shankha Satpathy, Corbin D. Jones, Michael J. Birrer, Xinpei Yi, Nathan Edwards, Fei Ding, Jiang Qian, Ning Qu, Alicia Francis, Daniel Cui Zhou, Jakub Stawicki, Bing Zhang, Rodrigo Vargas Eguez, Tao Liu, Dave Tabor, Maureen Dyer, Brian J. Druker, Gilbert S. Omenn, Azra Krek, Meenakshi Anurag, Melissa Borucki, Mathangi Thiagarajan, Shirley Tsang, Shakti Ramkissoon, Alexey I. Nesvizhskii, Li Ding, Lyubomir Valkov Vasilev, Yifat Geffen, James Suh, Tatiana S. Ermakova, Kakhaber Zaalishvili, Adel K. El-Naggar, Ki Sung Um, Ana I. Robles, Wen-Wei Liang, Richard D. Smith, Pei Wang, Emily S. Boja, Anna Calinawan, Yingwei Hu, Jiayi Ji, Renata Ferrarotto, Hongwei Liu, Jonathan T. Lei, Ramani B. Kothadia, Yize Li, Chelsea J. Newton, Anna Malovannaya, Steven A. Carr, Sandra Cerda, Yuriy Zakhartsev, Stephanie De Young, Eric J. Jaehnig, Peter B. McGarvey, Yan Shi, David I. Heiman, Joseph C. Dort, Karin D. Rodland, Lili Blumenberg, Michael A. Gillette, Piotr A. Mieczkowski, Pankaj Vats, Chet Birger, Yongchao Dou, David Fenyö, Saravana M. Dhanasekaran, Pushpa Hariharan, Eunkyung An, Jeffrey R. Whiteaker, George Miles, Jan Lubinski, Shayan C. Avanessian, Samuel H. Payne, Amanda G. Paulovich, Dmitry Rykunov, Lyudmila Petrenko, Martin Hyrcza, Guo Ci Teo, Alissa M. Weaver, D. R. Mani, Houston Culpepper, Meghan C. Burke, Daniel W. Chan, Bo Wen, Nicollette Maunganidze, Elie Traer, Darlene Tansil, Simona Migliozzi, Luciano Garofano, Qing Kay Li, Donghui Tan, Lori J. Sokoll, Mehdi Mesri, Karna Robinson, Fulvio D'Angelo, Kimberly Elburn, Alexander R. Pico, Umut Ozbek, Michael Schnaubelt, Gad Getz, Francesca Petralia, Andrew G. Sikora, Kai Li, Elena V. Ponomareva, Arul M. Chinnaiyan, Robert Zelt, Jun Zhu, Midie Xu, Dimitar Dimitrov Pazardzhikliev, Negin Vatanian, Grace Zhao, Thomas F. Westbrook, Kyung-Cho Cho, Yuefan Wang, Jason E. McDermott, Jeffrey W. Tyner, William Bocik, Shilpi Singh, Stephen E. Stein, Nancy Roche, Alicia Karz, Shannon Richey, Tara Hiltke, Michael Vernon, Lijun Chen, Henry Rodriguez, Xiaoyu Song, Elizabeth R. Duffy, Lin S. Chen, Liwei Cao, Shrabanti Chowdhury, Marcin Cieślik, Michael C. Wendl, Scott D. Jewell, and Cristina E. Tognon
- Subjects
Adult ,Male ,Proteomics ,0301 basic medicine ,Cancer Research ,medicine.medical_treatment ,Cell ,Biology ,Article ,Young Adult ,03 medical and health sciences ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Cyclin-dependent kinase ,medicine ,Humans ,Aged ,Proteogenomics ,Aged, 80 and over ,Squamous Cell Carcinoma of Head and Neck ,Papillomavirus Infections ,Phosphoproteomics ,Immunotherapy ,Middle Aged ,medicine.disease ,Head and neck squamous-cell carcinoma ,Immune checkpoint ,ErbB Receptors ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Female - Abstract
We present a proteogenomic study of 108 human papilloma virus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs). Proteomic analysis systematically catalogs HNSCC-associated proteins and phosphosites, prioritizes copy number drivers, and highlights an oncogenic role for RNA processing genes. Proteomic investigation of mutual exclusivity between FAT1 truncating mutations and 11q13.3 amplifications reveals dysregulated actin dynamics as a common functional consequence. Phosphoproteomics characterizes two modes of EGFR activation, suggesting a new strategy to stratify HNSCCs based on EGFR ligand abundance for effective treatment with inhibitory EGFR monoclonal antibodies. Widespread deletion of immune modulatory genes accounts for low immune infiltration in immune-cold tumors, whereas concordant upregulation of multiple immune checkpoint proteins may underlie resistance to anti-programmed cell death protein 1 monotherapy in immune-hot tumors. Multi-omic analysis identifies three molecular subtypes with high potential for treatment with CDK inhibitors, anti-EGFR antibody therapy, and immunotherapy, respectively. Altogether, proteogenomics provides a systematic framework to inform HNSCC biology and treatment.
- Published
- 2021
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