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Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma

  1. Author:
    Clark, David J
    Dhanasekaran, Saravana M
    Petralia, Francesca
    Pan, Jianbo
    Song, Xiaoyu
    Hu, Yingwei
    da Veiga Leprevost, Felipe
    Reva, Boris
    Lih, Tung-Shing M
    Chang, Hui-Yin
    Ma, Weiping
    Huang, Chen
    Ricketts, Christopher J
    Chen, Lijun
    Krek, Azra
    Li, Yize
    Rykunov, Dmitry
    Li, Qing Kay
    Chen, Lin S
    Ozbek, Umut
    Vasaikar, Suhas
    Wu, Yige
    Yoo, Seungyeul
    Chowdhury, Shrabanti
    Wyczalkowski, Matthew A
    Ji, Jiayi
    Schnaubelt, Michael
    Kong, Andy
    Sethuraman, Sunantha
    Avtonomov, Dmitry M
    Ao, Minghui
    Colaprico, Antonio
    Cao, Song
    Cho, Kyung-Cho
    Kalayci, Selim
    Ma, Shiyong
    Liu, Wenke
    Ruggles, Kelly
    Calinawan, Anna
    Gümüs, Zeynep H
    Geizler, Daniel
    Kawaler, Emily
    Teo, Guo Ci
    Wen, Bo
    Zhang, Yuping
    Keegan, Sarah
    Li, Kai
    Chen, Feng
    Edwards, Nathan
    Pierorazio, Phillip M
    Chen, Xi Steven
    Pavlovich, Christian P
    Hakimi, A Ari
    Brominski, Gabriel
    Hsieh, James J
    Antczak, Andrzej
    Omelchenko, Tatiana
    Lubinski, Jan
    Wiznerowicz, Maciej
    Linehan, W Marston
    Kinsinger, Christopher R
    Thiagarajan,Mathangi
    Boja, Emily S
    Mesri, Mehdi
    Hiltke, Tara
    Robles, Ana I
    Rodriguez, Henry
    Qian, Jiang
    Fenyö, David
    Zhang, Bing
    Ding, Li
    Schadt, Eric
    Chinnaiyan, Arul M
    Zhang, Zhen
    Omenn, Gilbert S
    Cieslik, Marcin
    Chan, Daniel W
    Nesvizhskii, Alexey I
    Wang, Pei
    Zhang, Hui

  2. Author Address

    Department of Pathology, Johns Hopkins University, Baltimore, MD 21231, USA., Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA., Department of Genetics and Genomic Sciences and 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, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA., Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Washington University School of Medicine, St. Louis, MO 63110, USA., Department of Public Health Sciences, University of Chicago, Chicago, IL 60637, USA., Department of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, TX 77030, USA., Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USA., Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA., Department of Medicine, New York University School of Medicine, New York, NY 10016, USA., Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA., Departments of Medicine and Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA., Department of Biochemistry and Cellular Biology, Georgetown University, Washington, DC 20007, USA., Brady Urological Institute and Department of Urology, Johns Hopkins University, Baltimore, MD 21231, USA., Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA., Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Department of Urology, Poznan University of Medical Sciences, Szwajcarska 3, Poznan 61-285, Poland., Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Department of Genetics and Pathology, Pomeranian Medical University, Szczecin 71-252, Poland., International Institute for Molecular Oncology, Poznan 60-203, Poland; Poznan University of Medical Sciences, Poznan 60-701, Poland., Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Department of Ophthalmology, Johns Hopkins University, Baltimore, MD 21231, USA., Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA., Department of Genetics and Genomic Sciences and Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Sema4, Stamford, CT 06902, USA., Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA; Department of Internal Medicine, Human Genetics, and School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA., Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: mcieslik@med.mich.edu., Department of Pathology, Johns Hopkins University, Baltimore, MD 21231, USA. Electronic address: dchan@jhmi.edu., Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: nesvi@med.umich.edu., Department of Genetics and Genomic Sciences and Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: pei.wang@mssm.edu., Department of Pathology, Johns Hopkins University, Baltimore, MD 21231, USA. Electronic address: huizhang@jhu.edu.,
    1. Year: 2019
    2. Date: Oct 31
  2. Journal: Cell
    1. 179
    2. 4
    3. Pages: 964-983.e31
  4. Type of Article: Article
  5. ISSN: 0092-8674
  1. Abstract:

    To elucidate the deregulated functional modules that drive clear cell renal cell carcinoma (ccRCC), we performed comprehensive genomic, epigenomic, transcriptomic, proteomic, and phosphoproteomic characterization of treatment-naive ccRCC and paired normal adjacent tissue samples. Genomic analyses identified a distinct molecular subgroup associated with genomic instability. Integration of proteogenomic measurements uniquely identified protein dysregulation of cellular mechanisms impacted by genomic alterations, including oxidative phosphorylation-related metabolism, protein translation processes, and phospho-signaling modules. To assess the degree of immune infiltration in individual tumors, we identified microenvironment cell signatures that delineated four immune-based ccRCC subtypes characterized by distinct cellular pathways. This study reports a large-scale proteogenomic analysis of ccRCC to discern the functional impact of genomic alterations and provides evidence for rational treatment selection stemming from ccRCC pathobiology. Copyright © 2019 Elsevier Inc. All rights reserved.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.cell.2019.10.007
  3. PMID: 31675502
  4. View record in Web of Science®
  5. WOS: 000493898000014
  6. PII : S0092-8674(19)31123-7

Library Notes

  1. Fiscal Year: FY2019-2020
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