ctDNA transiting into urine is ultrashort and facilitates noninvasive liquid biopsy of HPV+ oropharyngeal cancer.

Autor: Bhambhani C; Department of Internal Medicine, Division of Hematology/Oncology., Kang Q; Department of Internal Medicine, Division of Hematology/Oncology., Hovelson DH; Michigan Center for Translational Pathology.; Department of Computational Medicine & Bioinformatics., Sandford E; Department of Internal Medicine, Division of Hematology/Oncology., Olesnavich M; Department of Internal Medicine, Division of Hematology/Oncology., Dermody SM; Department of Otolaryngology., Wolfgang J; Department of Internal Medicine, Division of Hematology/Oncology., Tuck KL; Department of Internal Medicine, Division of Hematology/Oncology., Brummel C; Department of Otolaryngology., Bhangale AD; Department of Otolaryngology., He K; Department of Internal Medicine, Division of Hematology/Oncology., Gutierrez MG; Department of Internal Medicine., Lindstrom RH; Department of Internal Medicine, Division of Hematology/Oncology., Liu CJ; Michigan Center for Translational Pathology.; Department of Pathology., Tuck M; Department of Internal Medicine, Division of Hematology/Oncology., Kandarpa M; Department of Internal Medicine, Division of Hematology/Oncology., Mierzwa M; Department of Radiation Oncology, and.; Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan, USA., Casper K; Department of Otolaryngology.; Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan, USA., Prince ME; Department of Otolaryngology.; Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan, USA., Krauss JC; Department of Internal Medicine, Division of Hematology/Oncology., Talpaz M; Department of Internal Medicine, Division of Hematology/Oncology., Henry NL; Department of Internal Medicine, Division of Hematology/Oncology.; Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan, USA., Giraldez MD; Department of Internal Medicine, Division of Hematology/Oncology.; Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío, Consejo Superior de Investigaciones Científicas, University of Seville, Seville, Spain., Ramnath N; Department of Internal Medicine, Division of Hematology/Oncology., Tomlins SA; Michigan Center for Translational Pathology.; Department of Pathology.; Department of Urology., Swiecicki PL; Department of Internal Medicine, Division of Hematology/Oncology.; Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan, USA., Brenner JC; Department of Otolaryngology.; Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan, USA.; Department of Pharmacology., Tewari M; Department of Internal Medicine, Division of Hematology/Oncology.; Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan, USA.; Department of Biomedical Engineering, and.; Center for Computational Biology and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA.
Jazyk: angličtina
Zdroj: JCI insight [JCI Insight] 2024 Feb 08; Vol. 9 (6). Date of Electronic Publication: 2024 Feb 08.
DOI: 10.1172/jci.insight.177759
Abstrakt: BACKGROUNDTransrenal 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.MethodsUsing whole-genome sequencing, we discovered that urine TR-ctDNA fragments across multiple cancer types are predominantly ultrashort (<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+ OPSCC) and confirmed that assaying ultrashort DNA is critical for sensitive cancer detection from urine samples.ResultsTR-ctDNA was concordant with plasma ctDNA for cancer detection in patients with HPV+ 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+ OPSCC.ConclusionOur 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.FundingNIH 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.
Databáze: MEDLINE