Researchers from the College of Michigan Well being Rogel Most cancers Heart have created a urine-based check that detects items of DNA fragments launched by head and neck tumors. The check may probably facilitate early detection of this most cancers kind, which at the moment doesn’t have a dependable screening technique.
Human papillomavirus (HPV) is well known for inflicting cervical most cancers, however is more and more discovered to trigger cancers within the mouth, throat and different head and neck areas.
Early detection is essential as a result of detecting a most cancers at an earlier stage can result in higher outcomes for sufferers.
Utilizing entire genome sequencing, the Rogel group confirmed that cell-free DNA fragments launched by tumor cells, that are handed on from the bloodstream into urine by way of the kidneys, are predominantly ultra-short, with fewer than 50 base pairs. Given their small measurement, these fragments are prone to be missed utilizing standard urine or blood-based liquid biopsy checks in detecting circulating tumor DNA (ctDNA).
The analysis was led by Muneesh Tewari, M.D., Ph.D., professor of hematology and oncology, J. Chad Brenner, Ph.D., affiliate professor of otolaryngology-head and neck surgical procedure, and Paul L. Swiecicki, M.D., affiliate medical director for the Oncology Scientific Trials Assist Unit at Rogel. Preliminary outcomes are printed in JCI Perception.
“On this examine we offer proof to assist the speculation that standard assays don’t detect ultrashort fragments present in urine, since they’re designed to focus on longer DNA fragments. Our workforce used an unconventional strategy to develop a urine check for HPV-positive head and neck most cancers ctDNA detection,” stated examine co-first writer and analysis specialist Chandan Bhambhani, Ph.D.
Nonetheless within the discovery part, this mail-in check has already been distributed for analysis functions to sufferers inside a hundred-plus miles from Ann Arbor, permitting scientists to collect important information on the efficacy of the at-home equipment. Individuals gather a urine pattern and have it shipped again to the U-M laboratory, the place the testing may be executed to detect the presence or absence of head and neck most cancers.
“Probably the most exceptional outcomes of this examine is that the check that has been developed has detected most cancers recurrences far sooner than would sometimes occur primarily based on medical imaging. As such, these promising outcomes have given us the arrogance to broaden the scope of the examine, in search of to increasing distribution even additional,” stated Brenner, co-senior writer of the examine.
Whereas preliminary research have centered on head and neck most cancers, the paper additionally describes a brand new technique that might be utilized to broaden the check to detect different cancers as properly. For instance, the authors present that the check can detect ctDNA within the urine of sufferers with breast most cancers and acute myeloid leukemia. This means new alternatives to additionally examine the applying of urine-based testing for these extra cancers.
“Many individuals usually are not conscious that urine carries details about many various most cancers varieties, though it’s made within the kidneys. Our findings in regards to the distinction in ctDNA fragment sizes and the check we developed for HPV-positive head and neck most cancers detection present essential info on how urine-based diagnostic assays may be developed for various cancers,” Bhambhani stated. “Additional, a lot of these checks are prone to have a a lot larger compliance in sufferers requiring follow-up testing publish therapy, because of the comfort of self-collection of samples, when in comparison with blood-based assays.”
Funding: NIH grants R33 CA229023, R21 CA225493; NIH/Nationwide Most cancers Institute grants U01 CA183848, R01 CA184153, and P30CA046592; American Most cancers Society RSG-18-062-01-TBG; American Most cancers Society Mission Increase grant MBGI-22-056-01-MBG; and the A. Alfred Taubman Medical Analysis Institute.
Authors: 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, and Muneesh Tewari
