Inter- and intra-tumor heterogeneity of genetic and immune profiles in inherited renal cell carcinoma
Mariko Tabata,
Yusuke Sato,
Yasunori Kogure,
Marni B. McClure,
Yuji Oshikawa-Kumade,
Yuki Saito,
Sumito Shingaki,
Yuta Ito,
Mitsuhiro Yuasa,
Junji Koya,
Kazushi Yoshida,
Takashi Kohno,
Yu Miyama,
Teppei Morikawa,
Kenichi Chiba,
Ai Okada,
Seishi Ogawa,
Tetsuo Ushiku,
Yuichi Shiraishi,
Haruki Kume,
Keisuke Kataoka
Affiliations
Mariko Tabata
Division of Molecular Oncology, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
Yusuke Sato
Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; Corresponding author
Yasunori Kogure
Division of Molecular Oncology, National Cancer Center Research Institute, Tokyo 104-0045, Japan
Marni B. McClure
Division of Molecular Oncology, National Cancer Center Research Institute, Tokyo 104-0045, Japan
Yuji Oshikawa-Kumade
Division of Molecular Oncology, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Diagnostic Division, Otsuka Pharmaceutical Co., Ltd., Tokushima 771-0182, Japan
Yuki Saito
Division of Molecular Oncology, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Department of Gastroenterology, Keio University School of Medicine, Tokyo 160-8582, Japan
Sumito Shingaki
Division of Molecular Oncology, National Cancer Center Research Institute, Tokyo 104-0045, Japan
Yuta Ito
Division of Molecular Oncology, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo 105-8471, Japan
Mitsuhiro Yuasa
Division of Molecular Oncology, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
Junji Koya
Division of Molecular Oncology, National Cancer Center Research Institute, Tokyo 104-0045, Japan
Kazushi Yoshida
Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan
Takashi Kohno
Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan
Yu Miyama
Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
Teppei Morikawa
Department of Diagnostic Pathology, NTT Medical Center Tokyo, Tokyo 141-8625, Japan
Kenichi Chiba
Division of Genome Analysis Platform Development, National Cancer Center Research Institute, Tokyo 104-0045, Japan
Ai Okada
Division of Genome Analysis Platform Development, National Cancer Center Research Institute, Tokyo 104-0045, Japan
Seishi Ogawa
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan; Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto 606-8501, Japan; Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institute, Stockholm 17177, Sweden
Tetsuo Ushiku
Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
Yuichi Shiraishi
Division of Genome Analysis Platform Development, National Cancer Center Research Institute, Tokyo 104-0045, Japan
Haruki Kume
Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
Keisuke Kataoka
Division of Molecular Oncology, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan; Corresponding author
Summary: Patients with von Hippel-Lindau disease (vHL) are at risk of developing spatially and temporally multiple clear cell renal cell carcinomas (ccRCCs), which offers a valuable opportunity to analyze inter- and intra-tumor heterogeneity of genetic and immune profiles within the same patient. Here, we perform whole-exome and RNA sequencing, digital gene expression, and immunohistochemical analyses for 81 samples from 51 ccRCCs of 10 patients with vHL. Inherited ccRCCs are clonally independent and have less genomic alterations than sporadic ccRCCs. Hierarchical clustering of transcriptome profiles shows two clusters with distinct immune signatures: immune hot and cold clusters. Interestingly, not only samples from the same tumors but also different tumors from the same patients tend to show a similar immune signature, whereas samples from different patients frequently exhibit different signatures. Our findings reveal the genetic and immune landscape of inherited ccRCCs, demonstrating the relevance of host factors in shaping anti-tumor immunity.
