Circulating DNA Fragments (ctDNA) Are Not Always Tumor Related.

Recent research efforts focus on circulating "tumor" DNA (ctDNA) fragments in the blood to develop diagnostic tests. 

Abundant literature highlights the lack of reproducibility, the poor sensitivity and limited clinical utility of these tests. 

Some ctDNA limitations stem from:

• Cancer is EXTREMELY HETEROGENEOUS. Cancer cells from different patients are substantially different from one another morphologically and genetically.
• Cancer cells from the same biopsy in a single patient are also SUBSTANTIALLY DIFFERENT from one another morphologically and genetically. 
• Within a single patient, cancer cell genetics change constantly day after day as they multiply.
• The ctDNA does not shed from cells in the earlier stages of cancer, but rather from the later stages of the disease when cancer tissue starts necrosis (1-3). 

These limitations of ctDNA raise questions about its clinical value for patients!

Finding circulating tumor DNA fragments in the blood is like sifting for a single grain of sand from among the countless on an ocean beach because of the huge amount of nonspecific cDNA from dead cells.