Author Interviews, Biomarkers, Cancer Research / 22.07.2016
Circulating Tumor DNA Size Enhances Liquid Biopsy Effectiveness
MedicalResearch.com Interview with:
Dr. Hunter R. Underhill MD, PhD
Department of Pediatrics, Division of Medical Genetics, Department of Radiology,
University of Utah, Salt Lake City, Utah
Department of Radiology and Department of Neurological Surgery
University of Washington
Seattle, Washington
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: When cells undergo cell death (i.e., apoptosis) the DNA has the potential to enter the circulation. This DNA is not contained within a cellular membrane and is known as "cell-free DNA." This is a naturally occurring process. The same process also occurs when malignant tumors grow and evolve. The deposition of cell-free DNA derived from tumors is known as "circulating tumor DNA." Analysis of circulating tumor DNA holds the promise of detecting, diagnosing, and monitoring response to therapy of cancers through a simple blood draw - the "liquid biopsy." The challenge has been isolation of circulating tumor DNA from the background of the naturally occurring cell-free DNA. This has been particularly difficult in non-metastatic solid tumors as circulating tumor DNA has been heretofore indistinguishable from normal cell-free DNA except for the occurrence of mutant alleles that commonly occur at a frequency below detection limits - the proverbial needle in a haystack.
Our study found a distinct size difference in DNA fragment length between circulating tumor DNA and cell-free DNA. Specifically, circulating tumor DNA is about 20-50 base pairs shorter than cell-free DNA originating from healthy cells. We were subsequently able to exploit this difference in size to enrich for circulating tumor DNA - essentially removing a large portion of the haystack that does not contain the needle to simplify the search.
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