A proteogenomic portrait of lung squamous cell carcinoma Journal Article


Authors: Satpathy, S.; Krug, K.; Jean Beltran, P. M.; Savage, S. R.; Petralia, F.; Kumar-Sinha, C.; Dou, Y.; Reva, B.; Kane, M. H.; Avanessian, S. C.; Vasaikar, S. V.; Krek, A.; Lei, J. T.; Jaehnig, E. J.; Omelchenko, T.; Geffen, Y.; Bergstrom, E. J.; Stathias, V.; Christianson, K. E.; Heiman, D. I.; Cieslik, M. P.; Cao, S.; Song, X.; Ji, J.; Liu, W.; Li, K.; Wen, B.; Li, Y.; Gümüş, Z. H.; Selvan, M. E.; Soundararajan, R.; Visal, T. H.; Raso, M. G.; Parra, E. R.; Babur, Ö; Vats, P.; Anand, S.; Schraink, T.; Cornwell, M.; Rodrigues, F. M.; Zhu, H.; Mo, C. K.; Zhang, Y.; da Veiga Leprevost, F.; Huang, C.; Chinnaiyan, A. M.; Wyczalkowski, M. A.; Omenn, G. S.; Newton, C. J.; Schurer, S.; Ruggles, K. V.; Fenyö, D.; Jewell, S. D.; Thiagarajan, M.; Mesri, M.; Rodriguez, H.; Mani, S. A.; Udeshi, N. D.; Getz, G.; Suh, J.; Li, Q. K.; Hostetter, G.; Paik, P. K.; Dhanasekaran, S. M.; Govindan, R.; Ding, L.; Robles, A. I.; Clauser, K. R.; Nesvizhskii, A. I.; Wang, P.; Carr, S. A.; Zhang, B.; Mani, D. R.; Gillette, M. A.; Clinical Proteomic Tumor Analysis Consortium
Article Title: A proteogenomic portrait of lung squamous cell carcinoma
Abstract: 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. © 2021 The Author(s)
Keywords: protein; lung cancer; phosphorylation; proteomics; genomics; acetylation; squamous; ubiquitylation; proteogenomics; cptac
Journal Title: Cell
Volume: 184
Issue: 16
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2021-08-05
Start Page: 4348
End Page: 4371.e40
Language: English
DOI: 10.1016/j.cell.2021.07.016
PROVIDER: scopus
PUBMED: 34358469
PMCID: PMC8475722
DOI/URL:
Notes: Article -- Export Date: 1 September 2021 -- Source: Scopus
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  1. Paul K Paik
    255 Paik