Footprint From Cell-free DNA May Indicate Origin of Cancer in Liquid Biopsies

Footprint From Cell-free DNA May Indicate Origin of Cancer in Liquid Biopsies
Footprint From Cell-free DNA May Indicate Origin of Cancer in Liquid Biopsies

A new study suggests that cell-free DNA, tiny fragments of cells in the bloodstream that occur after cells die, may indicate the tissue-of-origin of a cancer, which can be unknown in some cases of metastatic disease. This research was published in Cell (doi:10.1016/j.cell.2015.11.050).

Liquid biopsies are being developed to use body fluids, typically blood, to detect and monitor cancer, as well as other conditions.

This study shows a new potential for expanding the role of liquid biopsy. The new approach analyzes the fragmentation pattern of cell-free DNA from 1 person and compares it with what might be expected for cell death associated with various medical or physiologic conditions.

"Our findings suggest it is possible to identify tissues contributing to cell-free DNA by looking at these fragmentation patterns, instead of looking for specific mutations in the DNA," said Jay Shendure, MD, PhD, of the department of genome science at the University of Washington in Seattle.

The test works by examining the ends of each DNA fragment and seeking hotspots, parts of the DNA that get cut more frequently than others.

Some parts of DNA get cut more frequently due to their positioning on nucleosomes. A nucleosome is a protein core that DNA is wrapped around like thread around a spool. The entire length of the genome has nucleosomes, like beads on a string, with the DNA looping around 1 nucleosome after another. The nucleosomes are positioned slightly differently in each cell type in the body, so the cell-free DNA has tell-tale marks depending on where it came from.

The research team demonstrated that nucleosome fingerprints in cell-free DNA were different from different types of cancer, based on work with blood samples from cancer patients. The researchers were able to identify the anatomical source of the tumor for some of the cancers.

"This could be particularly relevant in the 5% of metastatic cancers whose original source is unknown," Shendure said, adding that the test could help identify the type of cancer and guide treatment.

The researchers explained that, while most liquid biopsy approaches look for specific DNA mismatches between different cells in the body to detect mutations in tumor cells, this new test offers the advantage of working even when the cells are genetically identical to each other.

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