{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:47:57Z","timestamp":1782452877858,"version":"3.54.5"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Urology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"ABSTRACT<\/jats:title>\n \n Objectives<\/jats:title>\n Urothelial carcinoma (UC) is a common malignancy; however, UC subtypes\/divergent differentiation (S\/DD) accounts for only 10%\u201320% of overall cases. S\/DD's aggressive biological behavior significantly affects its prognosis and therapeutic decision\u2010making; thus, elucidating its genomic landscape within UC is important. This retrospective observational study aimed to evaluate and compare the molecular characteristics of S\/DD and pure urothelial carcinoma (PUC).<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Comprehensive cancer genomic profiling data were obtained from the Center for Cancer Genomics and Advanced Therapeutics (C\u2010CAT) and the MSK2022 dataset. The association between S\/DD and clinicopathological features was evaluated in an independent Hiroshima University cohort.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Across both C\u2010CAT and MSK2022 datasets,\n TP53<\/jats:italic>\n and\n RB1<\/jats:italic>\n mutations were more prevalent in S\/DD, whereas\n KDM6A<\/jats:italic>\n ,\n ARID1A<\/jats:italic>\n , and\n FGFR3<\/jats:italic>\n mutations were more common in PUC. High\u2010frequency copy number alterations included\n MYC<\/jats:italic>\n and\n RB1<\/jats:italic>\n in S\/DD, and\n CDKN2A<\/jats:italic>\n ,\n CDKN2B<\/jats:italic>\n ,\n CCND1<\/jats:italic>\n ,\n FGF19<\/jats:italic>\n ,\n FGF4<\/jats:italic>\n , and\n FGF3<\/jats:italic>\n in PUC. In the Hiroshima University cohort, S\/DD was associated with adverse clinicopathological features and a poor prognosis. Immunohistochemistry demonstrated a positive correlation of S\/DD with PD\u2010L1, EGFR, and p53 expression in upper tract UC tissues, and an inverse correlation with FGFR3, GATA3, Nectin4, and TROP2 expression.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Using a large\u2010scale Japanese genomic panel dataset, we characterized the molecular alterations associated with S\/DD. S\/DD frequently exhibits low Nectin\u20104 expression and basal\u2010like molecular features, which may have implications for treatment selection and inform future therapeutic strategies.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/iju.70538","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T08:05:48Z","timestamp":1780905948000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive Genomic Characterization Between Urothelial Carcinoma Subtypes\/Divergent Differentiation (S\/\n DD<\/scp>\n ) and Pure Urothelial Carcinoma Using a Large\u2010Scale Japanese Genomic Panel Dataset"],"prefix":"10.1111","volume":"33","author":[{"given":"Go","family":"Kobayashi","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Faculty of Pharmacy Yasuda Women's University Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Sekino","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8397-115X","authenticated-orcid":false,"given":"Shunsuke","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2098-3916","authenticated-orcid":false,"given":"Kohei","family":"Kobatake","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2223-2403","authenticated-orcid":false,"given":"Hiroyuki","family":"Kitano","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Goto","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Goriki","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Hieda","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Testutaro","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Sentani","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7014-6812","authenticated-orcid":false,"given":"Nobuyuki","family":"Hinata","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2020.09.004"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12965"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.05.008"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2025.04.008"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3233\/BLC-150037"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.04.048"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2019.12.002"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000002077"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-59888-8"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-22-0417"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111859"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-021-03239-7"},{"key":"e_1_2_12_14_1","first-page":"94","article-title":"ANXA10 Expression Is Inversely Associated With Tumor Stage, Grade, and TP53 Expression in Upper and Lower Urothelial Carcinoma","volume":"1","author":"Kobayashi G.","year":"2022","journal-title":"Pathobiology"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/pin.13274"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428\u2010025\u201004164\u20109"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-026-06250-2"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2009.09.048"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-014-0721-3"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/17588359231192402"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2024.100424"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0127908"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.13319"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-024-03224-3"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-021-00776-z"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-021-08078-y"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2025.09.003"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2023.06.006"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2024.0024"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.10.016"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm11111147"}],"container-title":["International Journal of Urology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/iju.70538","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/iju.70538","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/iju.70538","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:18:47Z","timestamp":1782451127000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/iju.70538"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":30,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1111\/iju.70538"],"URL":"https:\/\/doi.org\/10.1111\/iju.70538","archive":["Portico"],"relation":{},"ISSN":["0919-8172","1442-2042"],"issn-type":[{"value":"0919-8172","type":"print"},{"value":"1442-2042","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"2026-03-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70538"}}