{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:12:44Z","timestamp":1789776764156,"version":"4.0.1"},"reference-count":28,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>Molecular characterization of anatomically distinct urothelial carcinoma in the upper tract (UTUC) and bladder (UCB) has been challenging because of the rarity of UTUC. However, recent advances in real-world data curation have facilitated the generation of larger UTUC cohorts. In this study, we investigated the somatic, germline, and immunologic landscapes of UTUC compared with UCB.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS<\/jats:title>\n            <jats:p>From the Tempus Database, we retrospectively analyzed 505 UTUC and 2,416 UCB cases. Tumors were sequenced using Tempus xT DNA and xR RNA assays. Pathogenic somatic mutations, immune cell infiltration, tumor mutational burden (TMB), PD-L1, microsatellite instability (MSI), and mismatch repair (MMR) were evaluated. Potential germline alterations were assessed in 46 genes for patients with tumor\/normal matched sequencing (UTUC, n = 285; UCB, n = 1,359).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>\n              Alterations in\n              <jats:italic toggle=\"yes\">TERT, TP53, RB1, ERBB2,<\/jats:italic>\n              and\n              <jats:italic toggle=\"yes\">CDKN1A<\/jats:italic>\n              were more frequent in UCB, whereas\n              <jats:italic toggle=\"yes\">KMT2D, FGFR3, CDKN2B, KRAS<\/jats:italic>\n              , and\n              <jats:italic toggle=\"yes\">MYC<\/jats:italic>\n              were more frequent in UTUC. Germline variants were found in 4.8% of UCB and 5.6% of UTUC, with trends toward higher Lynch syndrome\u2013associated gene alterations (\n              <jats:italic toggle=\"yes\">MLH1, MSH2, MSH6, PMS2<\/jats:italic>\n              ) in UTUC (0.6%\n              <jats:italic toggle=\"yes\">v<\/jats:italic>\n              1.8%,\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              = .059). The prevalence of TMB \u226510 mut\/Mb was higher in UCB (17%\n              <jats:italic toggle=\"yes\">v<\/jats:italic>\n              11%,\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt; .001). UCB had higher PD-L1 positivity (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              = .013), whereas UTUC had more MSI-high (UTUC = 3.2%\n              <jats:italic toggle=\"yes\">v<\/jats:italic>\n              UCB = 1%,\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              = .001) and MMR-deficient (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              = .020) cases. CD4\n              <jats:sup>+<\/jats:sup>\n              and regulatory T-cell infiltrates were similar in both.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>By comprehensive molecular characterization of UC, we observed distinct genomic alterations and tumor microenvironment patterns in UTUC and UCB. Further research is warranted to elucidate the clinical implications of these findings. We compared the genetic and immune features of upper tract and bladder cancers. Our study found key differences that could affect treatment decisions, such as specific gene changes and immune markers. These insights may help doctors personalize therapies and improve patient care.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/po-25-00289","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T19:59:09Z","timestamp":1754596749000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":5,"title":["Comprehensive Comparison of Somatic, Germline, and Immune Cell Profiles in Upper Tract and Bladder Urothelial Carcinoma"],"prefix":"10.1200","author":[{"given":"Kit","family":"Yuen","sequence":"first","affiliation":[{"name":"UC San Diego Health, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4512-4106","authenticated-orcid":true,"given":"Margaret","family":"Meagher","sequence":"additional","affiliation":[{"name":"UC San Diego Health, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Mercer","sequence":"additional","affiliation":[{"name":"Tempus AI, Inc, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8845-5390","authenticated-orcid":true,"given":"Binyam","family":"Yilma","sequence":"additional","affiliation":[{"name":"Tempus AI, Inc, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Stoppler","sequence":"additional","affiliation":[{"name":"Tempus AI, Inc, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stamatina","family":"Fragkogianni","sequence":"additional","affiliation":[{"name":"Tempus AI, Inc, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2485-6201","authenticated-orcid":true,"given":"Nataliya","family":"Mar","sequence":"additional","affiliation":[{"name":"University of California Irvine, Irvine, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3701-5084","authenticated-orcid":true,"given":"Arash Rezazadeh","family":"Kalebasty","sequence":"additional","affiliation":[{"name":"University of California Irvine, Irvine, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8775-503X","authenticated-orcid":true,"given":"Shilpa","family":"Gupta","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Taussig Cancer Institute, Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3965-3394","authenticated-orcid":true,"given":"Petros","family":"Grivas","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3358-1193","authenticated-orcid":true,"given":"Aditya","family":"Bagrodia","sequence":"additional","affiliation":[{"name":"UC San Diego Health, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0581-7963","authenticated-orcid":true,"given":"Rana","family":"Mckay","sequence":"additional","affiliation":[{"name":"UC San Diego Health, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8170-264X","authenticated-orcid":true,"given":"Tyler","family":"Stewart","sequence":"additional","affiliation":[{"name":"UC San Diego Health, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3884-6322","authenticated-orcid":true,"given":"Amirali","family":"Salmasi","sequence":"additional","affiliation":[{"name":"UC San Diego Health, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.euf.2020.08.001"},{"key":"e_1_3_5_3_2","first-page":"15","article-title":"Differences between upper tract urothelial carcinoma and bladder cancer","volume":"26","author":"Singla N","year":"2021","unstructured":"Singla N, Margulis V: Differences between upper tract urothelial carcinoma and bladder cancer. 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