DNA Tags, Blood Tests Advance Cancer Care, Precision Medicine 

Georgetown Lombardi Comprehensive Cancer Center researchers are studying DNA tags in blood-based tests to better assess and treat cancer and other diseases using precision medicine.

During cell death, cell-free DNA (cfDNA) sheds from tissue and can then be isolated from a blood sample. Through this approach, researchers can study cell death across the body in both normal and cancer cells without the need for invasive biopsy samples, creating a better patient experience.

"Taking tumor tissue biopsies is a hit or miss process and is usually not a good representation of the whole tumor or its spread," Anton Wellstein, MD, PhD, said in a press release. "Using blood, or liquid biopsies, on the other hand, provides a homogeneous representation of cfDNA that is being shed from all types of cells."

Methyl groups, short fragments of DNA and chemical modifications to the fragments, show researchers what cell type the respective snippet of DNA came from due to the unique patterns of specific cell types.

Researchers can analyze data showing how the cell issue reacts to treatment by using cfDNA to compare the damage done to cells from various forms of treatment to undamaged cells from the same tissue. This information can assess what treatment is most effective, leading to better precision medicine.

"Fine-tuning these applications of cfDNA analysis is challenging and requires in-depth approaches, both at the genome sequencing level and computationally," the lead author of the article Megan Barefoot said.

"Methylated cfDNA has opened a new and minimally invasive way to detect damage to cells in the body as there are often hundreds of methyl markers per cell that can mark, very specifically, where the cells came from, much like a barcode scanner at a grocery checkout tells the store the identity of a particular product. Combined biological and computational analyses make deciphering these methylation patterns/molecular barcodes possible so that researchers can trace the origins of cfDNA."

This analysis will assist researchers in determining the tissue of origin of a cancer cell. Additionally, researchers could identify where damage originated, especially if it was due to treatment, by comparing damaged cells and healthy cells.

"This approach can be applied to any therapy that will impact tissue equilibrium by causing cells in tissues to become damaged and die, including chemotherapy, radiation, and immunotherapy. This review really helps set the stage for our future research efforts," said Wellstein, who is also a professor of oncology and pharmacology at Georgetown Lombardi and the corresponding author for this article.

"My lab is very actively pursuing methods and technologies that further refine analyses of methylated cfDNA. We believe these efforts are affordable and will soon become standard in labs and they should make a difference in advancing the understanding and treatment of many cancers."