DNA tags enable blood-based tests to assess cancer treatment outcomes


Date:
July 27, 2021
Source:
Georgetown University Medical Center
Summary:
Cell-free DNA (cfDNA) shed into the blood was discovered in the
late 1940s but with rapid advances in genomics and computational
analytics in just the past few years, researchers now believe that
studying tags, or modifications to this type of DNA, may lead to
a better understanding of how to assess, and possibly modulate,
treatment approaches for cancer and other diseases.



FULL STORY ========================================================================== Cell-free DNA (cfDNA) shed into the blood was discovered in the late
1940s but with rapid advances in genomics and computational analytics in
just the past few years, researchers at Georgetown Lombardi Comprehensive Cancer Center now believe that studying tags, or modifications to this
type of DNA, may lead to a better understanding of how to assess,
and possibly modulate, treatment approaches for cancer and other
diseases. Their perspective, drawn from a review of studies to date,
appears July 27 in Frontiers in Genetics.


========================================================================== During cell death, which is a normal part of tissue regeneration, cfDNA
is shed from tissue. The shed cfDNA can be isolated from a blood sample,
thus providing a reading of cell death across the body in both normal
and cancer cells without the need for taking invasive biopsy samples.

"Taking tumor tissue biopsies is a hit or miss process and is usually
not a good representation of the whole tumor or its spread," says Anton Wellstein, MD, PhD, professor of oncology and pharmacology at Georgetown Lombardi and corresponding author for this article. "Using blood, or
liquid biopsies, on the other hand, provides a homogeneous representation
of cfDNA that is being shed from all types of cells." The scientists
note that short fragments of DNA and chemical modifications to those
fragments, known as methyl groups, help tell researchers what cell type
the respective snippet of DNA came from because these methylation patterns
are unique to specific cell types. By using cfDNA to compare damage to
cells from various forms of treatment with undamaged normal cells from
the same tissue, the researchers can analyze a treasure-trove of data
about how the cells in a tissue are affected by treatments and other
external forces. This knowledge could be key in assessing if a therapy
is effective and what adverse effects it may cause.

"Fine-tuning these applications of cfDNA analysis is challenging
and requires in-depth approaches, both at the genome sequencing
level and computationally," explains Megan Barefoot, a MD/PhD
student in the Wellstein lab at the Cancer Center and lead author
of the article. "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." The end-result of these analyses aids investigators
in determining the tissue of origin of a cancer, for example, and also
allows researchers, when comparing damaged cells to healthy cells, to
see where the damage originated, especially if it was due to a certain
type of treatment.

"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," concludes Wellstein. "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." Georgetown University has a patent application,
with Wellstein and Barefoot as named inventors, on some of the aspects mentioned in the article.

This work was supported in part by funding from the National Institutes
of Health (T32 CA009686, F30 CA250307, R01 CA23129, and P30 CA51008).

========================================================================== Story Source: Materials provided by
Georgetown_University_Medical_Center. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Megan E. Barefoot, Netanel Loyfer, Amber J. Kiliti, A. Patrick
McDeed,
Tommy Kaplan, Anton Wellstein. Detection of Cell Types Contributing
to Cancer From Circulating, Cell-Free Methylated DNA. Frontiers
in Genetics, 2021; 12 DOI: 10.3389/fgene.2021.671057 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/07/210727110212.htm

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