EBioMedicine (Jun 2023)
Comparative analyses define differences between BHD-associated renal tumour and sporadic chromophobe renal cell carcinomaResearch in context
- Ryosuke Jikuya,
- Todd A. Johnson,
- Kazuhiro Maejima,
- Jisong An,
- Young-Seok Ju,
- Hwajin Lee,
- Kyungsik Ha,
- WooJeung Song,
- Youngwook Kim,
- Yuki Okawa,
- Shota Sasagawa,
- Yuki Kanazashi,
- Masashi Fujita,
- Seiya Imoto,
- Taku Mitome,
- Shinji Ohtake,
- Go Noguchi,
- Sachi Kawaura,
- Yasuhiro Iribe,
- Kota Aomori,
- Tomoyuki Tatenuma,
- Mitsuru Komeya,
- Hiroki Ito,
- Yusuke Ito,
- Kentaro Muraoka,
- Mitsuko Furuya,
- Ikuma Kato,
- Satoshi Fujii,
- Haruka Hamanoue,
- Tomohiko Tamura,
- Masaya Baba,
- Toshio Suda,
- Tatsuhiko Kodama,
- Kazuhide Makiyama,
- Masahiro Yao,
- Brian M. Shuch,
- Christopher J. Ricketts,
- Laura S. Schmidt,
- W. Marston Linehan,
- Hidewaki Nakagawa,
- Hisashi Hasumi
Affiliations
- Ryosuke Jikuya
- 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
- Todd A. Johnson
- Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan
- Kazuhiro Maejima
- Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan
- Jisong An
- Graduate School of Medical Science and Engineering (GSMSE), Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea
- Young-Seok Ju
- Graduate School of Medical Science and Engineering (GSMSE), Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea
- Hwajin Lee
- Biomedical Knowledge Engineering Laboratory, Seoul National University, Seoul, 08826, Republic of Korea
- Kyungsik Ha
- UPPThera, Inc. BRC Laboratory 1-204 9, Songdomirae-ro, Yeonsu-gu, Incheon, Republic of Korea
- WooJeung Song
- UPPThera, Inc. BRC Laboratory 1-204 9, Songdomirae-ro, Yeonsu-gu, Incheon, Republic of Korea
- Youngwook Kim
- National Cancer Center Korea, 323 Ilsan-ro, Ilsandong-gu, Goyang-si Gyeonggi-do, Republic of Korea
- Yuki Okawa
- Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan
- Shota Sasagawa
- Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan
- Yuki Kanazashi
- 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
- Seiya Imoto
- Human Genome Center, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan
- Taku Mitome
- Department of Urology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
- Shinji Ohtake
- Department of Urology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
- Go Noguchi
- Department of Urology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
- Sachi Kawaura
- Department of Urology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
- Yasuhiro Iribe
- Department of Urology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
- Kota Aomori
- Department of Urology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
- Tomoyuki Tatenuma
- Department of Urology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
- Mitsuru Komeya
- Department of Urology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
- Hiroki Ito
- Department of Urology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
- Yusuke Ito
- Department of Urology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
- Kentaro Muraoka
- Department of Urology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
- Mitsuko Furuya
- Pathology Center, GeneticLab Co., Ltd., 28-196, N9, W15, Chuo-ku, Sapporo, 060-0009, Japan
- Ikuma Kato
- Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
- Satoshi Fujii
- Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
- Haruka Hamanoue
- Clinical Genetics Department, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, 236-0004, Japan
- Tomohiko Tamura
- 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
- 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
- Kazuhide Makiyama
- Department of Urology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
- Masahiro Yao
- Department of Urology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
- Brian M. Shuch
- Institute of Urologic Oncology, UCLA School of Medicine, Los Angeles, CA90095, USA
- Christopher J. Ricketts
- Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD20892, USA
- Laura S. Schmidt
- 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
- W. Marston Linehan
- Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD20892, USA
- Hidewaki Nakagawa
- Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan; Corresponding author. 1-17-22 Suehiro-cho, East research building 4F, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
- Hisashi Hasumi
- Department of Urology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan; Corresponding author. 3-9 Fuku-ura, Room A623, Kanazawa-ku, Yokohama 236-0004, Japan.
- Journal volume & issue
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Vol. 92
p. 104596
Abstract
Summary: Background: 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. Methods: 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. Findings: 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. Interpretation: These data further our understanding of renal tumourigenesis of these two different types of renal tumours with similar histology. Funding: 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.
