Skip NavigationSkip to Content
Return Return to Search Results

Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma

  1. Author:
    Gillette, Michael A
    Satpathy, Shankha
    Cao, Song
    Dhanasekaran, Saravana M
    Vasaikar, Suhas V
    Krug, Karsten
    Petralia, Francesca
    Li, Yize
    Liang, Wen-Wei
    Reva, Boris
    Krek, Azra
    Ji, Jiayi
    Song, Xiaoyu
    Liu, Wenke
    Hong, Runyu
    Yao, Lijun
    Blumenberg, Lili
    Savage, Sara R
    Wendl, Michael C
    Wen, Bo
    Li, Kai
    Tang, Lauren C
    MacMullan, Melanie A
    Avanessian, Shayan C
    Kane, M Harry
    Newton, Chelsea J
    Cornwell, MacIntosh
    Kothadia, Ramani B
    Ma, Weiping
    Yoo, Seungyeul
    Mannan, Rahul
    Vats, Pankaj
    Kumar-Sinha, Chandan
    Kawaler, Emily A
    Omelchenko, Tatiana
    Colaprico, Antonio
    Geffen, Yifat
    Maruvka, Yosef E
    da Veiga Leprevost, Felipe
    Wiznerowicz, Maciej
    Gümüs, Zeynep H
    Veluswamy, Rajwanth R
    Hostetter, Galen
    Heiman, David I
    Wyczalkowski, Matthew A
    Hiltke, Tara
    Mesri, Mehdi
    Kinsinger, Christopher R
    Boja, Emily S
    Omenn, Gilbert S
    Chinnaiyan, Arul M
    Rodriguez, Henry
    Li, Qing Kay
    Jewell, Scott D
    Thiagarajan,Mathangi
    Getz, Gad
    Zhang, Bing
    Fenyö, David
    Ruggles, Kelly V
    Cieslik, Marcin P
    Robles, Ana I
    Clauser, Karl R
    Govindan, Ramaswamy
    Wang, Pei
    Nesvizhskii, Alexey I
    Ding, Li
    Mani, D R
    Carr, Steven A

  2. Author Address

    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., Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA. Electronic address: shankha@broadinstitue.org., Department of Medicine and Genetics, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA., Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA., Department of Translational Molecular Pathology, MD Anderson Cancer Center, 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 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., Institute for Systems Genetics and Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA., Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, 77030, USA., Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA; Department of Biological Sciences, Columbia University, New York, NY, 10027, USA., Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA; Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA, 90089, USA., Van Andel Research Institute, Grand Rapids, MI, 49503, USA., Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Department of Public Health Sciences, University of Miami, Miller School of Medicine, Miami, FL, 33136, USA., Poznan University of Medical Sciences, Poznan, 61-701, Poland; International Institute for Molecular Oncology, Poznan, 60-203, Poland., Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD, 20892, USA., Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA., Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, MD, 21224, USA., Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA., Division of Oncology and Siteman Cancer Center, Washington University School of Medicine in St. Louis, St. Louis, MO, 63110, 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., Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA. Electronic address: scarr@broad.mit.edu.,
    1. Year: 2020
    2. Date: Jul 09
  2. Journal: Cell
    1. 182
    2. 1
    3. Pages: 200-225.e35
  4. Type of Article: Article
  5. ISSN: 0092-8674
  1. Abstract:

    To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization of 110 tumors and 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, and acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, and gender. Proteomic and phosphoproteomic data illuminated biology downstream of copy number aberrations, somatic mutations, and fusions and identified therapeutic vulnerabilities associated with driver events involving KRAS, EGFR, and ALK. Immune subtyping revealed a complex landscape, reinforced the association of STK11 with immune-cold behavior, and underscored a potential immunosuppressive role of neutrophil degranulation. Smoking-associated LUADs showed correlation with other environmental exposure signatures and a field effect in NATs. Matched NATs allowed identification of differentially expressed proteins with potential diagnostic and therapeutic utility. This proteogenomics dataset represents a unique public resource for researchers and clinicians seeking to better understand and treat lung adenocarcinomas. Copyright © 2020 Elsevier Inc. All rights reserved.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1016/j.cell.2020.06.013
  3. PMID: 32649874
  4. View record in Web of Science®
  5. WOS: 000549184500018
  6. PII : S0092-8674(20)30744-3

Library Notes

  1. Fiscal Year: FY2019-2020
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel