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Single-cell transcriptomes underscore genetically distinct tumor characteristics and microenvironment for hereditary kidney cancers

  1. Author:
    Jikuya, Ryosuke
    Murakami, Koichi
    Nishiyama, Akira
    Kato, Ikuma
    Furuya, Mitsuko
    Nakabayashi, Jun
    Ramilowski, Jordan A
    Hamanoue, Haruka
    Maejima, Kazuhiro
    Fujita, Masashi
    Mitome, Taku
    Ohtake, Shinji
    Noguchi, Go
    Kawaura, Sachi
    Odaka, Hisakazu
    Kawahara, Takashi
    Komeya, Mitsuru
    Shinoki, Risa
    Ueno, Daiki
    Ito, Hiroki
    Ito, Yusuke
    Muraoka, Kentaro
    Hayashi, Narihiko
    Kondo, Keiichi
    Nakaigawa, Noboru
    Hatano, Koji
    Baba, Masaya
    Suda, Toshio
    Kodama, Tatsuhiko
    Fujii, Satoshi
    Makiyama, Kazuhide
    Yao, Masahiro
    Shuch, Brian M
    Schmidt,Laura
    Linehan, W Marston
    Nakagawa, Hidewaki
    Tamura, Tomohiko
    Hasumi, Hisashi

  2. Author Address

    Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan., Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan., Department of Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan., Advanced Medical Research Center, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan., Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan., Clinical Genetics Department, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan., Department of Urology, Osaka University Graduate School of Medicine, Osaka 565-0871 Japan., Laboratory of Cancer Metabolism, International Research Center for Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan., Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153-8904, Japan., Institute of Urologic Oncology, UCLA School of Medicine, Los Angeles, CA 90095, USA., Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.,
    1. Year: 2022
    2. Date: Jun 17
    3. Epub Date: 2022 05 25
  2. Journal: iScience
    1. 25
    2. 6
    3. Pages: 104463
  4. Type of Article: Article
  5. Article Number: 104463
  1. Abstract:

    Our understanding of how each hereditary kidney cancer adapts to its tissue microenvironment is incomplete. Here, we present single-cell transcriptomes of 108,342 cells from patient specimens including from six hereditary kidney cancers. The transcriptomes displayed distinct characteristics of the cell of origin and unique tissue microenvironment for each hereditary kidney cancer. Of note, hereditary leiomyomatosis and renal cell carcinoma (HLRCC)-associated kidney cancer retained some characteristics of proximal tubules, which were completely lost in lymph node metastases and present as an avascular tumor with suppressed T cells and TREM2-high macrophages, leading to immune tolerance. Birt-Hogg-Dubé (BHD)-associated kidney cancer exhibited transcriptomic intratumor heterogeneity (tITH) with increased characteristics of intercalated cells of the collecting duct and upregulation of FOXI1-driven genes, a critical transcription factor for collecting duct differentiation. These findings facilitate our understanding of how hereditary kidney cancers adapt to their tissue microenvironment. © 2022 The Author(s).

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External Sources

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  2. DOI: 10.1016/j.isci.2022.104463
  3. PMID: 35874919
  4. PMCID: PMC9301876
  5. PII : S2589-0042(22)00734-9

Library Notes

  1. Fiscal Year: FY2021-2022
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