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Satpathy S, Krug K, Jean Beltran PM, et al. A proteogenomic portrait of lung squamous cell carcinoma. Cell. 2021;184(16):4348-4371.e40doi: 10.1016/j.cell.2021.07.016.
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, �. �., 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. (2021). A proteogenomic portrait of lung squamous cell carcinoma. Cell, 184(16), 4348-4371.e40. https://doi.org/10.1016/j.cell.2021.07.016
Satpathy, Shankha, et al. "A proteogenomic portrait of lung squamous cell carcinoma." Cell vol. 184,16 (2021): 4348-4371.e40. doi: https://doi.org/10.1016/j.cell.2021.07.016
Satpathy S, Krug K, Jean Beltran PM, Savage SR, Petralia F, Kumar-Sinha C, Dou Y, Reva B, Kane MH, Avanessian SC, Vasaikar SV, Krek A, Lei JT, Jaehnig EJ, Omelchenko T, Geffen Y, Bergstrom EJ, Stathias V, Christianson KE, Heiman DI, Cieslik MP, Cao S, Song X, Ji J, Liu W, Li K, Wen B, Li Y, Gümüş ZH, Selvan ME, Soundararajan R, Visal TH, Raso MG, Parra ER, Babur Ö, Vats P, Anand S, Schraink T, Cornwell M, Rodrigues FM, Zhu H, Mo CK, Zhang Y, da Veiga Leprevost F, Huang C, Chinnaiyan AM, Wyczalkowski MA, Omenn GS, Newton CJ, Schurer S, Ruggles KV, Fenyö D, Jewell SD, Thiagarajan M, Mesri M, Rodriguez H, Mani SA, Udeshi ND, Getz G, Suh J, Li QK, Hostetter G, Paik PK, Dhanasekaran SM, Govindan R, Ding L, Robles AI, Clauser KR, Nesvizhskii AI, Wang P, Carr SA, Zhang B, Mani DR, Gillette MA. A proteogenomic portrait of lung squamous cell carcinoma. Cell. 2021 Aug 05;184(16):4348-4371.e40. doi: 10.1016/j.cell.2021.07.016. PMID: 34358469; PMCID: PMC8475722.
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Cell. 2021 Aug 05;184(16):4348-4371.e40. doi: 10.1016/j.cell.2021.07.016.

A proteogenomic portrait of lung squamous cell carcinoma.

Cell

Shankha Satpathy, Karsten Krug, Pierre M Jean Beltran, Sara R Savage, Francesca Petralia, Chandan Kumar-Sinha, Yongchao Dou, Boris Reva, M Harry Kane, Shayan C Avanessian, Suhas V Vasaikar, Azra Krek, Jonathan T Lei, Eric J Jaehnig, Tatiana Omelchenko, Yifat Geffen, Erik J Bergstrom, Vasileios Stathias, Karen E Christianson, David I Heiman, Marcin P Cieslik, Song Cao, Xiaoyu Song, Jiayi Ji, Wenke Liu, Kai Li, Bo Wen, Yize Li, Zeynep H Gümüş, Myvizhi Esai Selvan, Rama Soundararajan, Tanvi H Visal, Maria G Raso, Edwin Roger Parra, Özgün Babur, Pankaj Vats, Shankara Anand, Tobias Schraink, MacIntosh Cornwell, Fernanda Martins Rodrigues, Houxiang Zhu, Chia-Kuei Mo, Yuping Zhang, Felipe da Veiga Leprevost, Chen Huang, Arul M Chinnaiyan, Matthew A Wyczalkowski, Gilbert S Omenn, Chelsea J Newton, Stephan Schurer, Kelly V Ruggles, David Fenyö, Scott D Jewell, Mathangi Thiagarajan, Mehdi Mesri, Henry Rodriguez, Sendurai A Mani, Namrata D Udeshi, Gad Getz, James Suh, Qing Kay Li, Galen Hostetter, Paul K Paik, Saravana M Dhanasekaran, Ramaswamy Govindan, Li Ding, Ana I Robles, Karl R Clauser, Alexey I Nesvizhskii, Pei Wang, Steven A Carr, Bing Zhang, D R Mani, Michael A Gillette,

Affiliations

  1. Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA. Electronic address: [email protected].
  2. Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
  3. Lester and Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  4. Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  5. Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  6. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  7. Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  8. Sylvester Comprehensive Cancer Center and Department of Molecular and Cellular Pharmacology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
  9. Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
  10. Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA.
  11. Department of Population Health Science and Policy, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  12. Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
  13. Computer Science Department, University of Massachusetts Boston, Boston, MA 02125, USA.
  14. Institute for Systems Genetics and Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA.
  15. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
  16. Van Andel Research Institute, Grand Rapids, MI 49503, USA.
  17. Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
  18. Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA.
  19. Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21224, USA.
  20. Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA. Electronic address: [email protected].
  21. Lester and Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: [email protected].
  22. Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA. Electronic address: [email protected].
  23. Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA; Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA 02115, USA. Electronic address: [email protected].

PMID: 34358469 PMCID: PMC8475722 DOI: 10.1016/j.cell.2021.07.016

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.

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Keywords: CPTAC; acetylation; genomics; lung cancer; phosphorylation; protein; proteogenomics; proteomics; squamous; ubiquitylation

Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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