{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:08Z","timestamp":1787027768523,"version":"build-2736575974"},"reference-count":58,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T00:00:00Z","timestamp":1774137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Urothelial bladder cancer (UBC) is a molecularly heterogeneous disease, and most sequencing studies have relied on bladder-specific or solid tumor-restricted panels. Whether broader pan-cancer assays provide additional clinically relevant information remains unclear. Methods: We performed targeted next-generation sequencing using an extended gene panel on tumor samples from 100 patients with UBC treated at a tertiary center. Somatic single-nucleotide variants, small insertions\/deletions, copy-number alterations, and gene co-occurrence patterns were analyzed and correlated with clinicopathological features, disease-free survival (DFS), and overall survival (OS). Results: Recurrent alterations were identified in FGFR3 (\u224850%), TP53 (\u224835%), STAG2 (\u224825%), and PIK3CA (\u224820%), consistent with established molecular pathways in UBC. Less frequent but potentially actionable alterations, including mutations in BRCA1 and ALK, were also detected, reflecting the extended coverage of the panel. TP53 mutations were independently associated with worse OS, whereas STAG2 alterations were associated with improved OS, particularly in tumors without concurrent TP53 mutations. FGFR3 mutations showed a favorable but non-independent trend. No gene retained independent prognostic significance for DFS. Co-occurrence analysis revealed an FGFR3\/PIK3CA-associated pathway and relative mutual exclusivity between FGFR3 and TP53. Copy-number alterations were modest overall. Comparison with TCGA data demonstrated a higher frequency of FGFR3 alterations in our cohort, likely reflecting the larger proportion of non\u2013muscle-invasive tumors. Conclusions: Pan-cancer targeted sequencing provided a comprehensive genomic landscape of UBC, capturing canonical drivers and additional alterations that may be overlooked by bladder-restricted assays. The identification of TP53 and STAG2 as prognostic markers highlights the potential value of broader genomic profiling for biologically informed risk stratification in urothelial bladder cancer.<\/jats:p>","DOI":"10.3390\/cancers18061026","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T08:47:42Z","timestamp":1774255662000},"page":"1026","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pan-Cancer Targeted Sequencing Reveals Genomic Heterogeneity and Prognostic Subgroups in Urothelial Bladder Cancer"],"prefix":"10.3390","volume":"18","author":[{"given":"Dimitar","family":"Ugrinovski","sequence":"first","affiliation":[{"name":"Laboratory for Molecular Biology and Genomics, Institute of Biology, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University, 1000 Skopje, North Macedonia"},{"name":"PathoNext GmbH, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Skender","family":"Saidi","sequence":"additional","affiliation":[{"name":"University Clinic for Urology, Clinical Center, Medical Faculty, Ss. Cyril and Methodius University, 1000 Skopje, North Macedonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Stankov","sequence":"additional","affiliation":[{"name":"University Clinic for Urology, Clinical Center, Medical Faculty, Ss. Cyril and Methodius University, 1000 Skopje, North Macedonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7770-220X","authenticated-orcid":false,"given":"Martina","family":"Ambardjieva","sequence":"additional","affiliation":[{"name":"PHI University Clinic for Surgical Diseases St. Naum Ohridski, Skopje, Medical Faculty, Ss. Cyril and Methodius University, 1000 Skopje, North Macedonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2551-0368","authenticated-orcid":false,"given":"Slavica","family":"Josifovska","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Biology and Genomics, Institute of Biology, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University, 1000 Skopje, North Macedonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Katrin","family":"Koehler","sequence":"additional","affiliation":[{"name":"PathoNext GmbH, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg","family":"Gabert","sequence":"additional","affiliation":[{"name":"PathoNext GmbH, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6742-5212","authenticated-orcid":false,"given":"Sasho","family":"Panov","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Biology and Genomics, Institute of Biology, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University, 1000 Skopje, North Macedonia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,22]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.eururo.2021.08.010","article-title":"European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (Ta, T1, and Carcinoma in Situ)","volume":"81","author":"Babjuk","year":"2022","journal-title":"Eur. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Abbas, S., Shafik, R., Soomro, N., Heer, R., and Adhikari, K. (2025). 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