Chandan Bhambhani, Qing Kang, Daniel H Hovelson, Erin Sandford, Mary Olesnavich, Sarah M Dermody, Jenny Wolfgang, Kirsten L Tuck, Collin Brummel, Apurva D Bhangale, Kuang He, Marc G Gutierrez, Ryan H Lindstrom, Chia-Jen Liu, Melissa Tuck, Malathi Kandarpa, Michelle Mierzwa, Keith Casper, Mark E Prince, John C Krauss, Moshe Talpaz, N Lynn Henry, Maria D Giraldez, Nithya Ramnath, Scott A Tomlins, Paul L Swiecicki, J Chad Brenner, Muneesh Tewari
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...
February 8, 2024: JCI Insight