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A proteogenomic portrait of lung squamous cell carcinoma

  1. Author:
    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
    Gümüs, 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

  2. Author Address

    Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA. Electronic address: shankha@broadinstitute.org., Lester and Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA., 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., Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA., Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Sylvester Comprehensive Cancer Center and Department of Molecular and Cellular Pharmacology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA., 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., Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA., Department of Population Health Science and Policy, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA., Computer Science Department, University of Massachusetts Boston, Boston, MA 02125, USA., Institute for Systems Genetics and Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA., Van Andel Research Institute, Grand Rapids, MI 49503, USA., Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA., Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21224, USA., Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA. Electronic address: scarr@broad.mit.edu., Lester and Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: bing.zhang@bcm.edu., Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA. Electronic address: manidr@broadinstitute.org., 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: gillette@broadinstitute.org.,
    1. Year: 2021
    2. Date: Aug 05
  2. Journal: Cell
    1. 184
    2. 16
    3. Pages: 4348-4371.e40
  4. Type of Article: Article
  5. ISSN: 0092-8674
  1. 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.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.cell.2021.07.016
  3. PMID: 34358469
  4. View record in Web of Science®
  5. WOS: 000682521800018
  6. PII : S0092-8674(21)00857-6

Library Notes

  1. Fiscal Year: FY2020-2021
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