@article{fe249a428d7748019f6fec815292c9b0,
title = "Single-cell transcriptomes underscore genetically distinct tumor characteristics and microenvironment for hereditary kidney cancers",
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-Dub{\'e} (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.",
keywords = "Cancer, Cancer systems biology, Human specimen, Microenvironment, Oncology",
author = "Ryosuke Jikuya and Koichi Murakami and Akira Nishiyama and Ikuma Kato and Mitsuko Furuya and Jun Nakabayashi and Ramilowski, {Jordan A.} and Haruka Hamanoue and Kazuhiro Maejima and Masashi Fujita and Taku Mitome and Shinji Ohtake and Go Noguchi and Sachi Kawaura and Hisakazu Odaka and Takashi Kawahara and Mitsuru Komeya and Risa Shinoki and Daiki Ueno and Hiroki Ito and Yusuke Ito and Kentaro Muraoka and Narihiko Hayashi and Keiichi Kondo and Noboru Nakaigawa and Koji Hatano and Masaya Baba and Toshio Suda and Tatsuhiko Kodama and Satoshi Fujii and Kazuhide Makiyama and Masahiro Yao and Shuch, {Brian M.} and Schmidt, {Laura S.} and Linehan, {W. Marston} and Hidewaki Nakagawa and Tomohiko Tamura and Hisashi Hasumi",
note = "Funding Information: We thank Ms. Hiromi Soeda and Mr. Takayuki Akagi in the Department of Molecular Pathology, Yokohama City University for their excellent works in immunohistochemistry, and Drs. Shota Sasagawa, Yuki Okawa, and Todd Johnson in Laboratory for Cancer Genomics, RIKEN IMS, for their advice and assistance in bioinformatic analysis. Authors were supported by JSPS KAKENHI Grant Number as follows: H.Hasumi. by 19K09694, A.N. by 19K07372, I.K. by 19K16563, J.N. by 18K07204, Y.I. by 19K18591, H.I. by 20K18121 and 19K23781, M.K. by 21H03068, M.Furuya. by 20K07395, M.Y. by 19K09717, N.N. by 19K09676, K.K. by 20K09582, S.F. by 19K07769, T.T. by 21H02954, H.N. by 18H04049 and M.B. by 18H02938. This research was also supported by the MEXT Joint Usage/Research Center Program at the Advanced Medical Research Center, Yokohama City University, and the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research. This project was funded in part with federal funds from the Frederick National Laboratory for Cancer Research, NIH, under Contract HHSN261200800001E. The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. R.J. L.S.S. W.M.L. and H.Hasumi conceived the idea, designed the experiments, and wrote the paper. R.J. A.N. I.K. and M.Furuya, performed the experiments. R.J. K.Murakami, J.N. J.A.R. K.Maejima, M.Fujita, T.M. S.O. G.N. S.K. H.O. R.S. K.H. M.B. T.S. T.Kodama, S.F. M.Y. B.M.S. L.S.S. W.M.L. H.N. T.T. and H.Hasumi analyzed the data. R.J. H.Hamanoue, T.Kawahara, M.K. K.Muraoka, D.U. H.I. Y.I. N.H. K.K. N.N. K.Makiyama, and H.Hasumi collected specimens analyzed in this study. The authors declare no competing interests. Funding Information: We thank Ms. Hiromi Soeda and Mr. Takayuki Akagi in the Department of Molecular Pathology, Yokohama City University for their excellent works in immunohistochemistry, and Drs. Shota Sasagawa, Yuki Okawa, and Todd Johnson in Laboratory for Cancer Genomics, RIKEN IMS, for their advice and assistance in bioinformatic analysis. Authors were supported by JSPS KAKENHI Grant Number as follows: H.Hasumi. by 19K09694 , A.N. by 19K07372 , I.K. by 19K16563 , J.N. by 18K07204 , Y.I. by 19K18591 , H.I. by 20K18121 and 19K23781 , M.K. by 21H03068 , M.Furuya. by 20K07395 , M.Y. by 19K09717 , N.N. by 19K09676 , K.K. by 20K09582 , S.F. by 19K07769 , T.T. by 21H02954 , H.N. by 18H04049 and M.B. by 18H02938 . This research was also supported by the MEXT Joint Usage/Research Center Program at the Advanced Medical Research Center, Yokohama City University , and the Intramural Research Program of the National Institutes of Health (NIH) , National Cancer Institute (NCI) , Center for Cancer Research . This project was funded in part with federal funds from the Frederick National Laboratory for Cancer Research, NIH , under Contract HHSN261200800001E . The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = jun,
day = "17",
doi = "10.1016/j.isci.2022.104463",
language = "English",
volume = "25",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "6",
}
