Almost all of our cells are directly connected to the blood circulation.
Thousands of our cells die every hour and spill their contents into the circulation to be cleared by the liver and kidneys.
All blood samples will contain DNA from normal cells. If you have an infection, injury or inflammation you will have more DNA in your blood.
Based on this I don't understand the value of looking at cell free DNA from cancer patients as a potential diagnostic.
Some like to call it circulating tumor DNA (ctDNA), but can you really link any plasma DNA mutations to primary tumors or metastasis?
Good question. When levels of DNA into blood/serum are above "normal" levels and the DNA contains mutations in certain genes, together, this information can serve as the basis to investigate whether an individual or patient has abnormal cells that have potential to give rise to an aggressive tumor.
Hi Divaker,
According to some publications I have read, the "normal" concentration of serum DNA is ~13 ng/ml. In cancer patients it can be ~180 ng/ml.
http://cancerres.aacrjournals.org/content/61/4/1659.full
Cancer patients can have ~10X serum DNA compared to normal. In both cases we are talking about a LOT of DNA to cull through to find needles in multiple haystacks. Is there any way to tell which DNA fragments are directly from tumors?
Adding to the problem is that many cancer patients are already suffering from other disorders that also increase serum DNA.
Thrombosis/Pulmonary embolism:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3810974/
http://ccforum.biomedcentral.com/articles/10.1186/cc12735
Sepsis:
http://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-10-130
Bacterial infection:
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0087741
Viral infection:
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0031455
If you know, that the patient has a tumor with a certain mutation you can monitor the progression of the tumor and the response to therapy. Mutation testing in blood would be of advantage for inoperable tumorentities, when tissue is not available, but the information would be helpful for therapy. One problem is, that "useful" mutations are rare in special tumors. And if one cannot compare the "blood-result" to a "tissue-result", it is only an assumption, that the mutated DNA is from the found tumor (or metastases).
Hi Gudrun.
Everybody wants to know if cancer patients have certain tumor mutations so as to prescribe and monitor therapy, but the most direct way to evaluate tumor mutations is through biopsies.
If biopsies are not available and you have to rely on ctDNA analysis, just remember that this "analysis" is done by annealing plasma DNA fragments to DNA panel chips containing ~10K known DNA mutations.
Are these mutations specific to the cancer? Do you know the data processing of the results before you get them?
We may find circulating cancer cells by analyzing genetic cancer markers. One of my friends has started a company, Genomictree, with this concept. Please visit following site. http://genomictree.com/en/technology-2/dna-methylation/
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