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Comparative analyses define differences between BHD-associated renal tumour and sporadic chromophobe renal cell carcinoma

  1. Author:
    Jikuya, Ryosuke
    Johnson, Todd A
    Maejima, Kazuhiro
    An, Jisong
    Ju, Young-Seok
    Lee, Hwajin
    Ha, Kyungsik
    Song, WooJeung
    Kim, Youngwook
    Okawa, Yuki
    Sasagawa, Shota
    Kanazashi, Yuki
    Fujita, Masashi
    Imoto, Seiya
    Mitome, Taku
    Ohtake, Shinji
    Noguchi, Go
    Kawaura, Sachi
    Iribe, Yasuhiro
    Aomori, Kota
    Tatenuma, Tomoyuki
    Komeya, Mitsuru
    Ito, Hiroki
    Ito, Yusuke
    Muraoka, Kentaro
    Furuya, Mitsuko
    Kato, Ikuma
    Fujii, Satoshi
    Hamanoue, Haruka
    Tamura, Tomohiko
    Baba, Masaya
    Suda, Toshio
    Kodama, Tatsuhiko
    Makiyama, Kazuhide
    Yao, Masahiro
    Shuch, Brian M
    Ricketts, Christopher J
    Schmidt,Laura
    Linehan, W Marston
    Nakagawa, Hidewaki
    Hasumi, Hisashi

  2. Author Address

    Department of Urology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan; Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan., Graduate School of Medical Science and Engineering (GSMSE), Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea., Biomedical Knowledge Engineering Laboratory, Seoul National University, Seoul, 08826, Republic of Korea., UPPThera, Inc. BRC Laboratory 1-204 9, Songdomirae-ro, Yeonsu-gu, Incheon, Republic of Korea., National Cancer Center Korea, 323 Ilsan-ro, Ilsandong-gu, Goyang-si Gyeonggi-do, Republic of Korea., Human Genome Center, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan., Department of Urology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan., Pathology Center, GeneticLab Co., Ltd., 28-196, N9, W15, Chuo-ku, Sapporo, 060-0009, Japan., Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, 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, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan; Advanced Medical Research Center, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, 236-0004, 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, CA90095, USA., Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD20892, USA., Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD20892, USA; 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. Electronic address: hidewaki@riken.jp., Department of Urology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan. Electronic address: hasumi@yokohama-cu.ac.jp.,
    1. Year: 2023
    2. Date: May 12
    3. Epub Date: 2023 05 12
  2. Journal: EBioMedicine
    1. 92
    2. Pages: 104596
  4. Type of Article: Article
  5. Article Number: 104596
  1. Abstract:

    Birt-Hogg-Dubé (BHD) syndrome, caused by germline alteration of folliculin (FLCN) gene, develops hybrid oncocytic/chromophobe tumour (HOCT) and chromophobe renal cell carcinoma (ChRCC), whereas sporadic ChRCC does not harbor FLCN alteration. To date, molecular characteristics of these similar histological types of tumours have been incompletely elucidated. To elucidate renal tumourigenesis of BHD-associated renal tumours and sporadic renal tumours, we conducted whole genome sequencing (WGS) and RNA-sequencing (RNA-seq) of sixteen BHD-associated renal tumours from nine unrelated BHD patients, twenty-one sporadic ChRCCs and seven sporadic oncocytomas. We then compared somatic mutation profiles with FLCN variants and RNA expression profiles between BHD-associated renal tumours and sporadic renal tumours. RNA-seq analysis revealed that BHD-associated renal tumours and sporadic renal tumours have totally different expression profiles. Sporadic ChRCCs were clustered into two distinct clusters characterized by L1CAM and FOXI1 expressions, molecular markers for renal tubule subclasses. Increased mitochondrial DNA (mtDNA) copy number with fewer variants was observed in BHD-associated renal tumours compared to sporadic ChRCCs. Cell-of-origin analysis using WGS data demonstrated that BHD-associated renal tumours and sporadic ChRCCs may arise from different cells of origin and second hit FLCN alterations may occur in early third decade of life in BHD patients. These data further our understanding of renal tumourigenesis of these two different types of renal tumours with similar histology. This study was supported by JSPS KAKENHI Grants, RIKEN internal grant, and the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research. Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.

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  2. DOI: 10.1016/j.ebiom.2023.104596
  3. PMID: 37182269
  4. PII : S2352-3964(23)00161-5

Library Notes

  1. Fiscal Year: FY2022-2023
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