The key difference between cell free DNA and circulating tumor DNA is that cell free DNA is various forms of DNA that are freely circulating in the blood while circulating tumor DNA is the fragmented tumour-derived DNA that circulates in the blood.
Cell free DNA and circulating tumor DNA are two types of circulating nucleic acids. Circulating nucleic acids were discovered by Mandel and Metal in 1948. Later, it was discovered that the amount of circulating nucleic acids in diseased patients are significantly high. This discovery was first made in relation to lupus patients. Moreover, circulating nucleic acids have a higher prognostic value and can be used as a biomarker for detecting various diseases.
CONTENTS
1. Overview and Key Difference
2. What is Cell Free DNA
3. What is Circulating Tumor DNA
4. Similarities – Cell Free DNA and Circulating Tumor DNA
4. Cell Free DNA vs Circulating Tumor DNA in Tabular Form
5. Summary – Cell Free DNA vs Circulating Tumor DNA
What is Cell Free DNA?
Cell free DNA (Cf DNA) refers to various forms of DNA such as circulating tumor DNA, cell free mitochondrial DNA, and cell free fetal DNA, etc., that freely circulate in the blood. The elevated levels of cell free DNA are observed in advanced diseases such as cancer, trauma, sepsis, myocardial infarction, diabetes, stroke, sickle cell disease, etc. In addition to cancer and fetal medicine, cell free DNA is a useful biomarker for a multitude of ailments. This DNA can be used to detect transplant graft rejection as well. They are also used in determining ordinary stress, prenatal sex discernment, and in paternity testing.
Figure 01: Cell Free DNA
A cell free DNA is usually a double-stranded extracellular molecule of DNA. It consists of small fragments (50 to 200 bp) and larger fragments (21 kb). Furthermore, it has been already recognized as a reliable biomarker for the diagnosis of prostate and breast cancer. Cell free DNA predominantly circulates in the bloodstream as nucleosomes. Nucleosomes are nuclear complexes of histones and DNA. Cf DNA can be quantified using various techniques such as PCR, massively parallel sequencing, ultraviolet spectrometry, PicoGreen staining, and ELISA. As Cf DNA detection in the bloodstream is a rapid, easy, non-invasive, repetitive method, in future, it will be a potential biomarker for diagnosing numerous diseases like autoimmune rheumatic diseases and tumors.
What is Circulating Tumor DNA?
Circulating tumor DNA (Ct DNA) is the fragmented tumour-derived DNA that circulates in the blood. It has a tumor origin. As a circulating tumor may reflect the entire tumor genome, it has gained wide attraction for its potential utility in clinical setups. Liquid biopsies, which draw blood, may be used to test circulating tumors.
Figure 02: Circulating Tumor DNA
The biological processes that are likely involved in releasing Ct DNA include apoptosis and necrosis from dying cells or active release from tumor cells. In healthy tissues, infiltrating phagocytes can clear Ct DNA. Furthermore, various techniques can be used in analyzing circulating tumor DNA such as droplet digital PCR, BEAMing, CAPP-Seq (deep sequencing), Safe-sequencing, and duplex sequencing.
What are the Similarities Between Cell Free DNA and Circulating Tumor DNA?
- Cell free DNA and circulating tumor DNA are two types of circulating nucleic acids.
- They are made up of nucleotides.
- Both types can be used as potential markers to diagnose various diseases in clinical setups.
- They are found in the bloodstream.
- Both are extracellular forms of DNA molecules.
- They are both cleared up by infiltrating phagocytes.
What is the Difference Between Cell Free DNA and Circulating Tumor DNA?
Cell free DNA are various forms of DNA such as circulating tumor DNA, cell free mitochondrial DNA and cell free fetal DNA, etc., that freely circulate in the blood, while circulating tumor DNA is the fragmented tumour-derived DNA that circulates in the blood. So, this is the key difference between cell free DNA and circulating tumor DNA. Furthermore, cell free DNA circulates in fragments ranging from 50-220 bp while circulating tumor DNA circulates in fragments ranging from 134-144 bp.
The following infographic presents the difference between cell free DNA and circulating tumor DNA in tabular form for side by side comparison.
Summary – Cell Free DNA vs Circulating Tumor DNA
Circulating nucleic acids is thrown into bloodstream through regulated or fortuitous mechanisms. Cell free DNA and circulating tumor DNA are two types of circulating nucleic acids. Cell free DNA are various forms of DNA such as circulating tumor DNA, cell free mitochondrial DNA, cell free fetal DNA that freely circulate in the blood while circulating tumor DNA is the fragmented tumor derived DNA that circulates in the blood. Thus, this summarizes the difference between cell free DNA and circulating tumor DNA.
Reference:
1. Suraj, Shankar, et al. “Circulating Nucleic Acids: An Analysis of Their Occurrence in Malignancies.” Biomedical Reports, D.A. Spandidos, Jan. 2017.
2. “What Is Circulating Tumor DNA and How Is It Used to Diagnose and Manage Cancer?” MedlinePlus, U.S. National Library of Medicine, 28 July 2021.
Image Courtesy:
1. “Cell-free donor-derived DNA” By NIH Image Gallery (CC BY-NC 2.0) via Flickr
2. “CtDNA in circulation” By Racheljunewong – Own work (CC BY-SA 4.0) via Commons Wikimedia