Comparative transcriptome atlas as an assistive modality for complex classification of rare kidney cancers

Ryosuke Jikuya, Todd A. Johnson, Erika Muraoka, Go Noguchi, Shigekatsu Maekawa, Wataru Obara, Kazuyuki Numakura, Tomonori Habuchi, Kazuhiro Maejima, Shota Sasagawa, Yuki Kanazashi, Hwajin Lee, Woo Jeung Song, Hajime Sasagawa, Taku Mitome, Shinji Ohtake, Sachi Kawaura, Yasuhiro Iribe, Kota Aomori, Hirotaka Nagasaka, Tomoyuki Tatenuma, Daiki Ueno, Mitsuru Komeya, Hiroki Ito, Yusuke Ito, Kentaro Muraoka, Takashi Kawahara, Mitsuko Furuya, Ikuma Kato, Haruka Hamanoue, Akira Nishiyama, Tomohiko Tamura, Masaya Baba, Toshio Suda, Tatsuhiko Kodama, Takehiko Ogawa, Hiroji Uemura, Masahiro Yao, Toyonori Tsuzuki, Yoji Nagashima, Yuji Miura, Go Kimura, Seiya Imoto, Yukihide Momozawa, Satoshi Fujii, Kazuhide Makiyama, Takanori Hasegawa, Brian M. Shuch, Christopher J. Ricketts, Laura S. Schmidt, W. Marston Linehan, Hidewaki Nakagawa () and Hisashi Hasumi ()
Additional contact information
Ryosuke Jikuya: Yokohama City University Graduate School of Medicine, Department of Urology
Todd A. Johnson: RIKEN Center for Integrative Medical Sciences, Laboratory for Cancer Genomics
Erika Muraoka: Yokohama City University Graduate School of Medicine, Department of Molecular Pathology
Go Noguchi: Yokohama City University Graduate School of Medicine, Department of Urology
Shigekatsu Maekawa: Iwate Medical University, Department of Urology, School of Medicine
Wataru Obara: Iwate Medical University, Department of Urology, School of Medicine
Kazuyuki Numakura: Akita University Graduate School of Medicine, Department of Urology
Tomonori Habuchi: Akita University Graduate School of Medicine, Department of Urology
Kazuhiro Maejima: RIKEN Center for Integrative Medical Sciences, Laboratory for Cancer Genomics
Shota Sasagawa: RIKEN Center for Integrative Medical Sciences, Laboratory for Cancer Genomics
Yuki Kanazashi: RIKEN Center for Integrative Medical Sciences, Laboratory for Cancer Genomics
Hwajin Lee: Kyung Hee University, Department of Biomedical Science
Woo Jeung Song: Kyung Hee University, Department of Biomedical Science
Hajime Sasagawa: RIKEN Center for Integrative Medical Sciences, Laboratory for Genotyping Development
Taku Mitome: Yokohama City University Graduate School of Medicine, Department of Urology
Shinji Ohtake: Yokohama City University Graduate School of Medicine, Department of Urology
Sachi Kawaura: Yokohama City University Graduate School of Medicine, Department of Urology
Yasuhiro Iribe: Yokohama City University Graduate School of Medicine, Department of Urology
Kota Aomori: Yokohama City University Graduate School of Medicine, Department of Urology
Hirotaka Nagasaka: Yokohama City University Graduate School of Medicine, Department of Urology
Tomoyuki Tatenuma: Yokohama City University Graduate School of Medicine, Department of Urology
Daiki Ueno: Yokohama City University Graduate School of Medicine, Department of Urology
Mitsuru Komeya: Yokohama City University Graduate School of Medicine, Department of Urology
Hiroki Ito: Yokohama City University Graduate School of Medicine, Department of Urology
Yusuke Ito: Yokohama City University Graduate School of Medicine, Department of Urology
Kentaro Muraoka: Yokohama City University Graduate School of Medicine, Department of Urology
Takashi Kawahara: Yokohama City University Graduate School of Medicine, Department of Urology
Mitsuko Furuya: Hokkaido University Hospital, Department of Surgical Pathology
Ikuma Kato: Yokohama City University Graduate School of Medicine, Department of Molecular Pathology
Haruka Hamanoue: Yokohama City University Graduate School of Medicine, Clinical Genetics Department
Akira Nishiyama: Yokohama City University Graduate School of Medicine, Department of Immunology
Tomohiko Tamura: Yokohama City University Graduate School of Medicine, Department of Immunology
Masaya Baba: Kumamoto University, Laboratory of Cancer Metabolism, International Research Center for Medical Sciences
Toshio Suda: Kumamoto University, Laboratory of Cancer Metabolism, International Research Center for Medical Sciences
Tatsuhiko Kodama: University of Tokyo, Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology
Takehiko Ogawa: Yokohama City University, Department of Regenerative Medicine
Hiroji Uemura: Yokohama City University Graduate School of Medicine, Department of Urology
Masahiro Yao: Yokohama City University Graduate School of Medicine, Department of Urology
Toyonori Tsuzuki: Aichi Medical University Hospital, Department of Surgical Pathology
Yoji Nagashima: Tokyo Women’s Medical University, Department of Surgical Pathology
Yuji Miura: The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Department of Medical Oncology
Go Kimura: Nippon Medical School, Department of Urology
Seiya Imoto: University of Tokyo, Human Genome Center, Institute of Medical Science
Yukihide Momozawa: RIKEN Center for Integrative Medical Sciences, Laboratory for Genotyping Development
Satoshi Fujii: Yokohama City University Graduate School of Medicine, Department of Molecular Pathology
Kazuhide Makiyama: Yokohama City University Graduate School of Medicine, Department of Urology
Takanori Hasegawa: Institute of Science Tokyo, M&D Data Science Center, Institute of Integrated Research
Brian M. Shuch: UCLA School of Medicine, Institute of Urologic Oncology
Christopher J. Ricketts: National Institutes of Health, Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute
Laura S. Schmidt: National Institutes of Health, Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute
W. Marston Linehan: National Institutes of Health, Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute
Hidewaki Nakagawa: RIKEN Center for Integrative Medical Sciences, Laboratory for Cancer Genomics
Hisashi Hasumi: Yokohama City University Graduate School of Medicine, Department of Urology

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract There is a great unmet medical need for development of molecularly characterizing modalities to assist in the complex classification of rare kidney cancers, some of which are diagnosed as unclassified renal cell carcinoma (unclassified RCC) due to complex histology. Here we show utility of the comparative transcriptome atlas as an assistive modality for complex classification of rare kidney cancers. Whereas whole genome sequencing (WGS) of 52 rare kidney cancers identifies very few clinically significant variants in a subset of cases, unsupervised clustering results of RNA-seq data from 219 renal tumors including 140 rare kidney cancers are largely consistent with the histological classification based on WHO2022 classification. Additionally, the comparative transcriptome atlas may provide an opportunity to define the molecular characteristics of unclassified RCC and might predict patient outcome. These findings support the comparative transcriptome atlas as an assistive modality for complex classification of rare kidney cancers.

Date: 2025
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DOI: 10.1038/s41467-025-65303-z

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