Upper urinary tract urothelial carcinoma (UTUC) is one of the common urothelial cancers. Its molecular pathogenesis, however, is poorly understood, with no useful biomarkers available for accurate diagnosis and molecular classification. Through an integrated genetic study involving 199 UTUC samples, we delineate the landscape of genetic alterations in UTUC enabling genetic/molecular classification. According to the mutational status of TP53, MDM2, RAS, and FGFR3, UTUC is classified into five subtypes having discrete profiles of gene expression, tumor location/histology, and clinical outcome, which is largely recapitulated in an independent UTUC cohort. Sequencing of urine sediment-derived DNA has a high diagnostic value for UTUC with 82.2% sensitivity and 100% specificity. These results provide a solid basis for better diagnosis and management of UTUC.
Cancer cell. 2021 Jun 14 [Epub]
Yoichi Fujii, Yusuke Sato, Hiromichi Suzuki, Nobuyuki Kakiuchi, Tetsuichi Yoshizato, Andrew T Lenis, Shigekatsu Maekawa, Akira Yokoyama, Yasuhide Takeuchi, Yoshikage Inoue, Yotaro Ochi, Yusuke Shiozawa, Kosuke Aoki, Kenichi Yoshida, Keisuke Kataoka, Masahiro M Nakagawa, Yasuhito Nannya, Hideki Makishima, Jimpei Miyakawa, Taketo Kawai, Teppei Morikawa, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Genta Nagae, Masashi Sanada, Eiji Sugihara, Taka-Aki Sato, Tohru Nakagawa, Masashi Fukayama, Tetsuo Ushiku, Hiroyuki Aburatani, Satoru Miyano, Jonathan A Coleman, Yukio Homma, David B Solit, Haruki Kume, Seishi Ogawa
Department of Pathology and Tumor Biology, Kyoto University, Kyoto 606-8501, Japan; Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto 606-8501, Japan; Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan., Department of Pathology and Tumor Biology, Kyoto University, Kyoto 606-8501, Japan; Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan., Department of Pathology and Tumor Biology, Kyoto University, Kyoto 606-8501, Japan., Department of Pathology and Tumor Biology, Kyoto University, Kyoto 606-8501, Japan; Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto 606-8501, Japan., Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan., Department of Pathology and Tumor Biology, Kyoto University, Kyoto 606-8501, Japan; 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 113-8655, Japan., Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan., Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan., Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan., Department of Advanced Diagnosis, Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya 460-0001, Japan., Research and Development Center for Precision Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8550, Japan., Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; Department of Urology, Teikyo University School of Medicine, Tokyo 173-8606, Japan., Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan., Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; Department of Urology, Japanese Red Cross Medical Center, Tokyo 150-8935, Japan., Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Department of Pathology and Tumor Biology, 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. Electronic address: .