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

iScience

Ikuma Kato¹  Tomohiko Tamura²  Koichi Murakami³  Kazuhiro Maejima⁴  Haruka Hamanoue⁴  Masashi Fujita⁵  Akira Nishiyama⁶  Mitsuko Furuya⁶  Masahiro Yao⁷  Jun Nakabayashi⁷  Jordan A. Ramilowski⁷  Toshio Suda⁸  Risa Shinoki⁹  Keiichi Kondo⁹  Noboru Nakaigawa⁹  Narihiko Hayashi⁹  Mitsuru Komeya⁹  Kentaro Muraoka⁹  Koji Hatano⁹  Go Noguchi⁹  Takashi Kawahara⁹  Yusuke Ito⁹  Brian M. Shuch⁹  Sachi Kawaura⁹  Ryosuke Jikuya⁹  Masaya Baba⁹  Daiki Ueno⁹  Hisakazu Odaka⁹  Hiroki Ito⁹  Laura S. Schmidt⁹  W. Marston Linehan^1,10  Taku Mitome^1,11  Shinji Ohtake^1,11  Kazuhide Makiyama^1,12  Tatsuhiko Kodama^1,13  Satoshi Fujii^1,13  Hidewaki Nakagawa^1,14  Hisashi Hasumi^1,14 

[1] Advanced Medical Research Center, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan;Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA;Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan;Advanced Medical Research Center, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan;Clinical Genetics Department, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan;Department of Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan;Department of Molecular Pathology, 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;Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan;Institute of Urologic Oncology, UCLA School of Medicine, Los Angeles, CA 90095, USA;Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan;Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153-8904, Japan;Laboratory of Cancer Metabolism, International Research Center for Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan;Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA;

关键词: Oncology;    Microenvironment;    Human specimen;    Cancer systems biology;    Cancer;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown