Scientists at the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, have found a way of detecting early-stage cancer by analyzing short strands of cell-free DNA in urine.
Until recently, it was thought that DNA fragments in urine were degraded at random and were too short to provide any meaningful information about a disease as complex as cancer. But TGen and City of Hope researchers and their colleagues from Baylor University and Phoenix Children’s Hospital found that these DNA fragments are not random and can be used to differentiate between healthy individuals and those with cancer.
“There are many steps between where we are now and where we want to go — detecting cancer from a urine sample — but without doubt this is an encouraging first step,” said Muhammed Murtaza, Ph.D., an associate professor, co-director of TGen’s Center for Noninvasive Diagnostics, and the study’s senior author of the paper published this week in Science Translational Medicine.
Using a urine sample reduces the physical invasiveness to zero, Murtaza explained, and may eliminate a lab visit, given that the sample could be collected at home and mailed in for analysis.
By studying tissue samples from children with various cancers, whose malignancies often move extraordinarily fast, and adults with pancreatic cancer, whose early detection is critical to their disease outcomes, researchers mapped the DNA fragmentation profiles in their urine.
“We found that certain regions of the genome are protected from fragmentation in urine from healthy individuals, but the same regions are more fragmented in patients with cancer,” Murtaza said.
The fragmentation profiles were remarkably similar across multiple individuals. The length of the DNA fragments where similar, the regions of the genome where the fragmentation occurred were consistent, and informed researchers what type of cells contributed the fragments.
The researchers characterized the fragmentation patterns in urine cfDNA using whole genome sequencing (WGS). They found the size of the cfDNA fragments showed “multiple strong peaks between 40 and 120 base pairs, with a modal size of 81”. The properties they detected where “robust to preanalytical perturbations, such as at-home collection and delay in processing.”
In short, they write that WGS revealed “Protected regions (RPSs) conserved across individuals with partial overlap with nucleosome positioning maps inferred from plasma cfDNA.”
Ajay Goel, PhD, chair of the Department of Molecular Diagnostics and Experimental Therapeutics and Associate Director for Basic Science at City of Hope, an independent research and treatment center for cancer and diabetes, is one of the study’s authors.
“If the study results come to fruition, our urinalysis technology would be a remarkable breakthrough in the detection of many cancers, especially in pancreatic cancer,” Goel said. “If cancer is detected early, it could substantially lower the mortality rate for what is currently the third leading cause of cancer death in the U.S.”
While early results are promising, the researchers suggest test their findings must be tested in much larger populations of cancer patients and identify differences between men and women, young and old, and those with co-morbidities, such as diabetes and other chronic diseases.
“This is a fundamental new finding and provides a potentially dynamic path forward for the early diagnosis of cancer, given that urine is one of the easiest samples to collect,” said Daniel D. Von Hoff, MD, TGen Distinguished Professor and one of the paper’s authors. “If follow-on studies yield positive results, I could one day see this test becoming an integral part of one’s annual physical.”