{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:49:52Z","timestamp":1791352192875,"version":"4.3.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Non-muscle-invasive bladder cancer (NMIBC) is characterized by high recurrence rates, highlighting the need for effective, non-invasive diagnostic and risk stratification tools. Although urinary biomarkers are increasingly used worldwide, molecular data specific to Chinese NMIBC populations remain limited. This study explores the potential utility of TERT promoter and FGFR3 hotspot mutations detected in urinary tumor DNA (utDNA) in a prospective Chinese cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We prospectively enrolled 106 newly diagnosed NMIBC patients between February 2023 and August 2023 at Fudan University Shanghai Cancer Center (ChiCTR2300076543). First-morning urine samples were collected prior to TURBT. A PCR-based UI-Seek assay was employed to detect hotspot mutations in the promoter region (M1: c.-146 C&amp;gt;T, C250T; M2: c.-124 C&amp;gt;T, C228T) and FGFR3 gene (M1: c.742 C&amp;gt;T, p.R248C; M2: c.746 C&amp;gt;G, p.S249C).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The overall mutation rates for TERT promoter and FGFR3 were 49.06% and 15.09%, respectively, with a combined sensitivity of 55.66%. Compared with published study cohorts from Western countries and Japan, Chinese NMIBC patients showed differences in molecular mutation profiles. Notably, the TERT-M2 mutation was associated with tumor aggressiveness, with significant correlations observed for T1 stage (P\u00a0=\u00a00.011), high-grade tumors (P\u00a0=\u00a00.011), and high\/very high EAU risk categories (P &amp;lt; 0.001). In the subgroup of patients with rapid recurrence within 12 months, TERT promoter mutations (particularly M2), high-grade histology, T1 stage, and high\/very high EAU risk categories were significantly enriched. Conversely, FGFR3 mutations showed no significant correlation with clinicopathological parameters. Patients were stratified into early recurrence (\u226412 months, n = 14) and long-term recurrence-free (&amp;gt;24 months, n = 40) groups. T1 stage, high tumor grade, high\/very high-risk stratification, and TERT mutations (especially the TERT-M2 subtype) were significantly associated with early recurrence (P &amp;lt; 0.05), whereas sex, tumor multiplicity, presence of CIS, and FGFR3 mutations showed no significant correlation with recurrence timing (P &amp;gt; 0.05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study characterizes the mutational landscape of urinary tumor DNA (utDNA) in Chinese patients with non-muscle invasive bladder cancer (NMIBC). Our findings suggest that utDNA-based detection of TERT promoter mutations, particularly the M2 subtype, and FGFR3 mutations may provide complementary molecular information for recurrence risk assessment. Larger prospective multicenter studies are warranted to validate these findings and evaluate the clinical potential of utDNA as a non-invasive molecular tool in NMIBC management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1914617","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:50:19Z","timestamp":1791348619000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Population-specific molecular features and clinical significance of urinary tumor DNA mutations in Chinese patients with newly diagnosed non-muscle-invasive bladder cancer"],"prefix":"10.3389","volume":"16","author":[{"given":"Zugang","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Urology, Guangyuan Central Hospital of Sichuan Province","place":["Guangyuan, China"]},{"name":"Department of Urology, Fudan University Shanghai Cancer Center","place":["Shanghai, 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengming","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Urology, Fudan University Shanghai Cancer Center","place":["Shanghai, China"]},{"name":"Shanghai Medical College, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huina","family":"Wang","sequence":"additional","affiliation":[{"name":"Acornmed Biotechnology Co., Ltd","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingwei","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Urology, Fudan University Shanghai Cancer Center","place":["Shanghai, China"]},{"name":"Shanghai Medical College, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Urology, Fudan University 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