文章基本信息

标题：Single-cell transcriptomes underscore genetically distinct tumor characteristics and microenvironment for hereditary kidney cancers
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作者：Ryosuke Jikuya ; Koichi Murakami ; Akira Nishiyama 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：6
页码：1-20
DOI：10.1016/j.isci.2022.104463
语种：English
出版社：Elsevier
摘要：SummaryOur 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.Graphical abstractDisplay OmittedHighlights•scRNA-seq displayed genetically defined characteristics of hereditary kidney cancer•scRNA-seq revealed unique tissue microenvironment of each hereditary kidney cancer•BHD-associated kidney cancer showed transcriptomic intratumor heterogeneity (tITH)•BHD-associated kidney cancer showed intercalated cell characteristics driven by FOXI1Oncology; Microenvironment; Human specimen; Cancer systems biology; Cancer;