A proteogenomic portrait of lung squamous cell carcinoma

Satpathy, Shankha; Krug, Karsten; Jean Beltran, Pierre M.; Savage, Sara R.; Petralia, Francesca; Kumar-Sinha, Chandan; Dou, Yongchao; Reva, Boris; Kane, M. Harry; Avanessian, Shayan C.; Vasaikar, Suhas V.; Krek, Azra; Lei, Jonathan T.; Jaehnig, Eric J.; Omelchenko, Tatiana; Geffen, Yifat; Bergstrom, Erik J.; Stathias, Vasileios; Christianson, Karen E.; Heiman, David I.; Cieslik, Marcin P.; Cao, Song; Song, Xiaoyu; Ji, Jiayi; Liu, Wenke; Li, Kai; Wen, Bo; Li, Yize; Gümüş, Zeynep H.; Selvan, Myvizhi Esai; Soundararajan, Rama; Visal, Tanvi H.; Raso, Maria G.; Parra, Edwin Roger; Babur, Özgün; Vats, Pankaj; Anand, Shankara; Schraink, Tobias; Cornwell, MacIntosh; Rodrigues, Fernanda Martins; Zhu, Houxiang; Mo, Chia-Kuei; Zhang, Yuping; da Veiga Leprevost, Felipe; Huang, Chen; Chinnaiyan, Arul M.; Wyczalkowski, Matthew A.; Omenn, Gilbert S.; Newton, Chelsea J.; Schurer, Stephan; Ruggles, Kelly V.; Fenyö, David; Jewell, Scott D.; Thiagarajan, Mathangi; Mesri, Mehdi; Rodriguez, Henry; Mani, Sendurai A.; Udeshi, Namrata D.; Getz, Gad; Suh, James; Li, Qing Kay; Hostetter, Galen; Paik, Paul K.; Dhanasekaran, Saravana M.; Govindan, Ramaswamy; Ding, Li; Robles, Ana I.; Clauser, Karl R.; Nesvizhskii, Alexey I.; Wang, Pei; Carr, Steven A.; Zhang, Bing; Mani, D. R.; Gillette, Michael A.; Green, Alex; Molinolo, Alfredo; Francis, Alicia; Paulovich, Amanda G.; Karnuta, Andrii; Colaprico, Antonio; Hindenach, Barbara; Pruetz, Barbara L.; Kubisa, Bartosz; Druker, Brian J.; Huynh, Carissa; Goldthwaite, Charles A.; Birger, Chet; Kinsinger, Christopher R.; Jones, Corbin D.; Rohrer, Dan; Valley, Dana R.; Chan, Daniel W.; Chesla, David; Hansel, Donna; Ponomareva, Elena V.; Duffy, Elizabeth; Burks, Eric; Schadt, Eric E.; Fedorov, Eugene S.; An, Eunkyung; Ding, Fei; Wilson, George D.; Batra, Harsh; Zhang, Hui; Maas, Jennifer E.; Eschbacher, Jennifer; Ketchum, Karen A.; Rodland, Karin D.; Hoadley, Katherine A.; Suzuki, Kei; Um, Ki Sung; Qi, Liqun; Bernard, Lori; Wiznerowicz, Maciej; Wojtyś, Małgorzata; Domagalski, Marcin J.; Ellis, Matthew J.; Dyer, Maureen A.; Borucki, Melissa; Anurag, Meenakshi; Birrer, Michael J.; Xu, Midie; Krotevich, Mikhail; Roche, Nancy; Edwards, Nathan J.; Vatanian, Negin; Mucci, Neil R.; Maunganidze, Nicollette; Gabrovski, Nikolay; Potapova, Olga; Fadare, Oluwole; Grady, Pamela; McGarvey, Peter B.; Hariharan, Pushpa; Thangudu, Ratna R.; Montgomery, Rebecca; Pandurengan, Renganayaki; Smith, Richard D.; Welsh, Robert J.; Mareedu, Sailaja; Payne, Samuel H.; Cottingham, Sandra; Singh, Shilpi; Tsang, Shirley X.; Cai, Shuang; Gabriel, Stacey; Liu, Tao; Hiltke, Tara; Vashist, Tanmayi; Bauer, Thomas; Sovenko, Volodymyr; Tourtellotte, Warren G.; Ma, Weiping; Bocik, William; Hasan, Wohaib; Jing, Xiaojun; Tang, Ximing; Liao, Yuxing; Yvonne,; Shutack,; Zhang, Zhen; Hanhan, Ziad

doi:10.1016/j.cell.2021.07.016

Title: A proteogenomic portrait of lung squamous cell carcinoma

Journal Article · 04 August 2021 · Cell

DOI: https://doi.org/10.1016/j.cell.2021.07.016 · OSTI ID:2563609

Satpathy, Shankha ^[1]; Krug, Karsten; Jean Beltran, Pierre M.; Savage, Sara R.; Petralia, Francesca; Kumar-Sinha, Chandan; Dou, Yongchao; Reva, Boris; Kane, M. Harry; Avanessian, Shayan C.; Vasaikar, Suhas V.; Krek, Azra; Lei, Jonathan T.; Jaehnig, Eric J.; Omelchenko, Tatiana; Geffen, Yifat; Bergstrom, Erik J.; Stathias, Vasileios; Christianson, Karen E.; Heiman, David I. more »

Massachusetts Institute of Technology (MIT), Cambridge, MA (United States); Harvard University, Cambridge, MA (United States); et al.

Lung squamous cell carcinoma (LSCC) remains a leading cause of cancer death with few therapeutic options. We characterized the proteogenomic landscape of LSCC, providing a deeper exposition of LSCC biology with potential therapeutic implications. We identify NSD3 as an alternative driver in FGFR1-amplified tumors and low-p63 tumors overexpressing the therapeutic target survivin. SOX2 is considered undruggable, but our analyses provide rationale for exploring chromatin modifiers such as LSD1 and EZH2 to target SOX2-overexpressing tumors. Our data support complex regulation of metabolic pathways by crosstalk between post-translational modifications including ubiquitylation. Numerous immune-related proteogenomic observations suggest directions for further investigation. Proteogenomic dissection of CDKN2A mutations argue for more nuanced assessment of RB1 protein expression and phosphorylation before declaring CDK4/6 inhibition unsuccessful. Finally, triangulation between LSCC, LUAD, and HNSCC identified both unique and common therapeutic vulnerabilities. These observations and proteogenomics data resources may guide research into the biology and treatment of LSCC.

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Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE

Contributing Organization:: Clinical Proteomic Tumor Analysis Consortium

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 2563609

Report Number(s):: PNNL-SA--191486

Journal Information:: Cell, Journal Name: Cell Journal Issue: 16 Vol. 184; ISSN 0092-8674

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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Upregulation of Wnt signaling under hypoxia promotes lung cancer progression Hong, Chun-Fu; Chen, Wei-You; Wu, Cheng-Wen Oncology Reports, Vol. 38, Issue 3 https://doi.org/10.3892/or.2017.5807	journal	March 2017
NetMHCpan-4.0: Improved Peptide–MHC Class I Interaction Predictions Integrating Eluted Ligand and Peptide Binding Affinity Data Jurtz, Vanessa; Paul, Sinu; Andreatta, Massimo The Journal of Immunology, Vol. 199, Issue 9 https://doi.org/10.4049/jimmunol.1700893	journal	October 2017
Impact of acetylation on tumor metabolism Zhao, Di; Li, Fu-Long; Cheng, Zhou-Li Molecular & Cellular Oncology, Vol. 1, Issue 3 https://doi.org/10.4161/23723548.2014.963452	journal	September 2014
Nuclear PKM2 regulates the Warburg effect Yang, Weiwei; Lu, Zhimin Cell Cycle, Vol. 12, Issue 19 https://doi.org/10.4161/cc.26182	journal	October 2013

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