{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:47:11Z","timestamp":1791499631399,"version":"4.3.4"},"reference-count":25,"publisher":"American Society for Clinical Investigation","issue":"6","license":[{"start":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["CA229023"],"award-info":[{"award-number":["CA229023"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["CA225493"],"award-info":[{"award-number":["CA225493"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Cancer Institute","award":["CA183848"],"award-info":[{"award-number":["CA183848"]}]},{"name":"National Cancer Institute","award":["CA184153"],"award-info":[{"award-number":["CA184153"]}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"crossref","award":["RSG-18-062-01-TBG"],"award-info":[{"award-number":["RSG-18-062-01-TBG"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"crossref","award":["MBGI-22-056-01-MBG"],"award-info":[{"award-number":["MBGI-22-056-01-MBG"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Cancer Institute","award":["CA046592"],"award-info":[{"award-number":["CA046592"]}]},{"DOI":"10.13039\/100008456","name":"A. Alfred Taubman Medical Research Institute","doi-asserted-by":"crossref","award":["Taubman Scholar"],"award-info":[{"award-number":["Taubman Scholar"]}],"id":[{"id":"10.13039\/100008456","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,22]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Transrenal cell-free tumor DNA (TR-ctDNA), which transits from the bloodstream into urine, has the potential to enable noninvasive cancer detection for a wide variety of nonurologic cancer types.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using whole-genome sequencing, we discovered that urine TR-ctDNA fragments across multiple cancer types are predominantly ultrashort (&lt;50 bp) and, therefore, likely to be missed by conventional ctDNA assays. We developed an ultrashort droplet digital PCR assay to detect TR-ctDNA originating from HPV-associated oropharyngeal squamous cell carcinoma (HPV\n                      <jats:sup>+<\/jats:sup>\n                      OPSCC) and confirmed that assaying ultrashort DNA is critical for sensitive cancer detection from urine samples.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TR-ctDNA was concordant with plasma ctDNA for cancer detection in patients with HPV\n                      <jats:sup>+<\/jats:sup>\n                      OPSCC. As proof of concept for using urine TR-ctDNA for posttreatment surveillance, in a small longitudinal case series, TR-ctDNA showed promise for noninvasive detection of recurrence of HPV\n                      <jats:sup>+<\/jats:sup>\n                      OPSCC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our data indicate that focusing on ultrashort fragments of TR-ctDNA will be important for realizing the full potential of urine-based cancer diagnostics. This has implications for urine-based detection of a wide variety of cancer types and for facilitating access to care through at-home specimen collections.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Funding<\/jats:title>\n                    <jats:p>NIH grants R33 CA229023, R21 CA225493; NIH\/National Cancer Institute grants U01 CA183848, R01 CA184153, and P30CA046592; American Cancer Society RSG-18-062-01-TBG; American Cancer Society Mission Boost grant MBGI-22-056-01-MBG; and the A. Alfred Taubman Medical Research Institute.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci.insight.177759","type":"journal-article","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T08:26:26Z","timestamp":1712305586000},"source":"Crossref","is-referenced-by-count":26,"title":["ctDNA transiting into urine is ultrashort and facilitates noninvasive liquid biopsy of HPV+ oropharyngeal cancer"],"prefix":"10.1172","volume":"9","author":[{"given":"Chandan","family":"Bhambhani","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology\/Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology\/Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel H.","family":"Hovelson","sequence":"additional","affiliation":[{"name":"Michigan Center for Translational Pathology,"},{"name":"Department of Computational Medicine & Bioinformatics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Sandford","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology\/Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Olesnavich","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology\/Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M.","family":"Dermody","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Wolfgang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology\/Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten L.","family":"Tuck","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology\/Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Collin","family":"Brummel","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apurva D.","family":"Bhangale","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuang","family":"He","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology\/Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc G.","family":"Gutierrez","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan H.","family":"Lindstrom","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology\/Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Jen","family":"Liu","sequence":"additional","affiliation":[{"name":"Michigan Center for Translational Pathology,"},{"name":"Department of Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Tuck","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology\/Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malathi","family":"Kandarpa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology\/Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Mierzwa","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, and"},{"name":"Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Casper","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology,"},{"name":"Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Prince","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology,"},{"name":"Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Krauss","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology\/Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moshe","family":"Talpaz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology\/Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. 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