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Proteogenomic insights suggest druggable pathways in endometrial carcinoma

  1. Author:
    Dou, Yongchao
    Katsnelson, Lizabeth
    Gritsenko, Marina A
    Hu, Yingwei
    Reva, Boris
    Hong, Runyu
    Wang, Yi-Ting
    Kolodziejczak, Iga
    Lu, Rita Jui-Hsien
    Tsai, Chia-Feng
    Bu, Wen
    Liu, Wenke
    Guo, Xiaofang
    An, Eunkyung
    Arend, Rebecca C
    Bavarva, Jasmin
    Chen, Lijun
    Chu, Rosalie K
    Czekanski, Andrzej
    Davoli, Teresa
    Demicco, Elizabeth G
    DeLair, Deborah
    Devereaux, Kelly
    Dhanasekaran, Saravana M
    Dottino, Peter
    Dover, Bailee
    Fillmore, Thomas L
    Foxall, McKenzie
    Hermann, Catherine E
    Hiltke, Tara
    Hostetter, Galen
    Jedryka, Marcin
    Jewell, Scott D
    Johnson, Isabelle
    Kahn, Andrea G
    Ku, Amy T
    Kumar-Sinha, Chandan
    Kurzawa, Pawel
    Lazar, Alexander J
    Lazcano, Rossana
    Lei, Jonathan T
    Li, Yi
    Liao, Yuxing
    Lih, Tung-Shing M
    Lin, Tai-Tu
    Martignetti, John A
    Masand, Ramya P
    Matkowski, Rafal
    McKerrow, Wilson
    Mesri, Mehdi
    Monroe, Matthew E
    Moon, Jamie
    Moore, Ronald J
    Nestor, Michael D
    Newton, Chelsea
    Omelchenko, Tatiana
    Omenn, Gilbert S
    Payne, Samuel H
    Petyuk, Vladislav A
    Robles, Ana I
    Rodriguez, Henry
    Ruggles, Kelly V
    Rykunov, Dmitry
    Savage, Sara R
    Schepmoes, Athena A
    Shi, Tujin
    Shi, Zhiao
    Tan, Jimin
    Taylor, Mason
    Thiagarajan,Mathangi
    Wang, Joshua M
    Weitz, Karl K
    Wen, Bo
    Williams, C M
    Wu, Yige
    Wyczalkowski, Matthew A
    Yi, Xinpei
    Zhang, Xu
    Zhao, Rui
    Mutch, David
    Chinnaiyan, Arul M
    Smith, Richard D
    Nesvizhskii, Alexey I
    Wang, Pei
    Wiznerowicz, Maciej
    Ding, Li
    Mani, D R
    Zhang, Hui
    Anderson, Matthew L
    Rodland, Karin D
    Zhang, Bing
    Liu, Tao
    Fenyö, David

  2. Author Address

    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; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Institute for Systems Genetics, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA., Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA., Department of Pathology and Oncology, Johns Hopkins University, Baltimore, MD 21231, USA., Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., International Institute for Molecular Oncology, 20-203 Poznan, Poland; Postgraduate School of Molecular Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland., Department of Medicine and Genetics, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA., Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA., Division of Gynecologic Oncology, University of South Florida Morsani College of Medicine and Tampa General Hospital Cancer Institute, Tampa, FL 33606, USA., Office of Cancer Clinical Proteomics Research, National Cancer Institute, Rockville, MD 20850, USA., Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Alabama at Birmingham, Birmingham, AL 35249, USA., Environmental Molecular Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA., Wroclaw Medical University and Lower Silesian Oncology, Pulmonology and Hematology Center (DCOPIH), Wroclaw, Poland., Department of Pathology and Laboratory Medicine, Mount Sinai Hospital and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 1X5, Canada., Department of Pathology, NYU Grossman School of Medicine, New York, NY 10016, USA., Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA., Department of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, NYU Grossman School of Medicine, New York, NY 10016, USA., Van Andel Research Institute, Grand Rapids, MI 49503, USA., Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35249, USA., Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA., Heliodor Swiecicki Clinical Hospital in Poznan ul. Przybyszewskiego 49, 60-355 Poznan, Poland; Poznan University of Medical Sciences, 61-701 Poznan, Poland., Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA., Department of Pathology 160;& Immunology, Baylor College of Medicine, Houston, TX 77030, USA., The Rockefeller University, New York, NY 10065, USA., Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA; Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA; School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA., Department of Biology, Brigham Young University, Provo, UT 84602, USA., Institute for Systems Genetics, NYU Grossman School of Medicine, New York, NY 10016, USA; Division of Precision Medicine, Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA., Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA., Washington University School of Medicine, Saint Louis, MO 63110, USA., Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA., International Institute for Molecular Oncology, 60-203 Poznan, Poland; Heliodor Swiecicki Clinical Hospital in Poznan ul. Przybyszewskiego 49, 60-355 Poznan, Poland; Poznan University of Medical Sciences, 61-701 Poznan, Poland., Division of Gynecologic Oncology, University of South Florida Morsani College of Medicine and Tampa General Hospital Cancer Institute, Tampa, FL 33606, USA. Electronic address: mlander5@usf.edu., Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA; Department of Cell, Developmental, and Cancer Biology, Oregon Health 160;& Science University, Portland, OR 97221, USA. Electronic address: rodland@ohsu.edu., 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; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: bing.zhang@bcm.edu., Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA. Electronic address: tao.liu@pnnl.gov., Institute for Systems Genetics, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA. Electronic address: david@fenyolab.org.,
    1. Year: 2023
    2. Date: Sep 11
    3. Epub Date: 2023 08 02
  2. Journal: Cancer Cell
    1. 41
    2. 9
    3. Pages: 1586-1605.e15
  4. Type of Article: Article
  1. Abstract:

    We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity. PIK3R1 in-frame indels are associated with elevated AKT phosphorylation and increased sensitivity to AKT inhibitors. CTNNB1 hotspot mutations are concentrated near phosphorylation sites mediating pS45-induced degradation of ß-catenin, which may render Wnt-FZD antagonists ineffective. Deep learning accurately predicts EC subtypes and mutations from histopathology images, which may be useful for rapid diagnosis. Overall, this study identified molecular and imaging markers that can be further investigated to guide patient stratification for more precise treatment of EC. Published by Elsevier Inc.

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External Sources

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  2. DOI: 10.1016/j.ccell.2023.07.007
  3. PMID: 37567170
  4. PII : S1535-6108(23)00247-7

Library Notes

  1. Fiscal Year: FY2023-2024
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