Liquid Biopsy Cancer Markers: “Needle in a haystack” to “Hippo in a haystack”?

The entire picture of how cfDNA can be used as a footprint markers in liquid biopsy. [Shendure Lab/University of Washington]

The entire picture of how cfDNA can be used as a footprint markers in liquid biopsy. [Shendure Lab/University of Washington]

The main reason why cell-free circulating DNA (cfDNA) came in the focus in recent years in the field of molecular diagnosis, is because of its unique efficiency to detect or monitor the tumor progression inside the cancer patient. This concept is now being referred as “Liquid Biopsy” by the researchers worldwide. It is a technique in which cfDNA is isolated from patient’s blood and looked for the presence of “markers”. This new diagnosis technique seems interesting since it does not demand for invasive practices like biopsy sampling nor is it risky to perform.

However, despite all the advantages, the major problem that this technique is facing currently is the recovery of the “fragments of interest” in the downstream processing of cfDNA isolation. Not all the cfDNA isolated from cancer patient can have the mutation on it, and thus loss of such “fragments of interest” can lead to false negative results.

Jay Shendure, M.D., Ph.D., professor of genome sciences at the University of Washington, his newly published research in Cell press may help this field to overcome this big problem. This senior study author and Howard Hughes Medical Institute investigator Jay Shendure stated that “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”.

Entire genome sequence in each cell of a multicellular organism is static but it is folded and packed using histone proteins in a very unique fashion in each cell of the same organism. As tumor grows rapidly, the cell death rate increases in the same way. Entire cell gets degraded by apoptosis or necrosis, and DNA inside the nucleus gets chopped into small pieces except the intact nucleosomes. This leaves unique “cut-marks” on the cfDNA and these fingerprints can be used to trace the tissue of origin from which they are released.

So this could avoid the need of a “fragment of interest” in liquid biopsy technique, instead among those collected cfDNA many fragments all together can act as a markers for tumor detection.


References:

Snyder, Matthew W., et al. “Cell-free DNA Comprises an In Vivo Nucleosome Footprint that Informs Its Tissues-Of-Origin.” Cell 164.1 (2016): 57-68.

About Vikrant Palande

Hello, this is Vikrant. I am a PhD student at Bar Ilan University, Faculty of Medicine in the Galilee. My principal scientific interests are Cancer genomics and its diagnostic applications. I am involved in studying clinical relevance of cell-free circulating DNA (cfDNA) for diagnosis, staging, prognosis and therapeutic monitoring of Gliomas Tumors.