iScience (Jun 2022)
Single-cell transcriptomes underscore genetically distinct tumor characteristics and microenvironment for hereditary kidney cancers
- Ryosuke Jikuya,
- Koichi Murakami,
- Akira Nishiyama,
- Ikuma Kato,
- Mitsuko Furuya,
- Jun Nakabayashi,
- Jordan A. Ramilowski,
- Haruka Hamanoue,
- Kazuhiro Maejima,
- Masashi Fujita,
- Taku Mitome,
- Shinji Ohtake,
- Go Noguchi,
- Sachi Kawaura,
- Hisakazu Odaka,
- Takashi Kawahara,
- Mitsuru Komeya,
- Risa Shinoki,
- Daiki Ueno,
- Hiroki Ito,
- Yusuke Ito,
- Kentaro Muraoka,
- Narihiko Hayashi,
- Keiichi Kondo,
- Noboru Nakaigawa,
- Koji Hatano,
- Masaya Baba,
- Toshio Suda,
- Tatsuhiko Kodama,
- Satoshi Fujii,
- Kazuhide Makiyama,
- Masahiro Yao,
- Brian M. Shuch,
- Laura S. Schmidt,
- W. Marston Linehan,
- Hidewaki Nakagawa,
- Tomohiko Tamura,
- Hisashi Hasumi
Affiliations
- Ryosuke Jikuya
- 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
- Koichi Murakami
- 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
- Akira Nishiyama
- Department of Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
- Ikuma Kato
- Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
- Mitsuko Furuya
- Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
- Jun Nakabayashi
- Advanced Medical Research Center, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan
- Jordan A. Ramilowski
- Advanced Medical Research Center, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan
- Haruka Hamanoue
- Clinical Genetics Department, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
- Kazuhiro Maejima
- Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan
- Masashi Fujita
- Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan
- Taku Mitome
- Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
- Shinji Ohtake
- Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
- Go Noguchi
- Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
- Sachi Kawaura
- Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
- Hisakazu Odaka
- Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
- Takashi Kawahara
- Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
- Mitsuru Komeya
- Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
- Risa Shinoki
- Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
- Daiki Ueno
- Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
- Hiroki Ito
- Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
- Yusuke Ito
- Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
- Kentaro Muraoka
- Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
- Narihiko Hayashi
- Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
- Keiichi Kondo
- Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
- Noboru Nakaigawa
- Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
- Koji Hatano
- Department of Urology, Osaka University Graduate School of Medicine, Osaka 565-0871 Japan
- Masaya Baba
- Laboratory of Cancer Metabolism, International Research Center for Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan
- Toshio Suda
- Laboratory of Cancer Metabolism, International Research Center for Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan
- Tatsuhiko Kodama
- Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153-8904, Japan
- Satoshi Fujii
- Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
- Kazuhide Makiyama
- Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
- Masahiro Yao
- Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan
- Brian M. Shuch
- Institute of Urologic Oncology, UCLA School of Medicine, Los Angeles, CA 90095, USA
- Laura S. Schmidt
- 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
- W. Marston Linehan
- Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
- Hidewaki Nakagawa
- Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan
- Tomohiko Tamura
- 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
- Hisashi Hasumi
- Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan; Corresponding author
- Journal volume & issue
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Vol. 25,
no. 6
p. 104463
Abstract
Summary: 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.
