Tumor-specific genomic alterations can be used to detect circulating tumor DNA circulating (ctDNA). They represent specific biomarkers that distinguish cancer cells and normal cells. They are likely to be useful for the diagnosis, prognosis, treatment, and follow-up of cancer patients, but their use in clinical oncology requires a highly sensitive strategy that discriminates modified sequences in a large excess of DNA coming from normal cells [1, 2].
Picoliter droplet-based digital PCR allows performing millions of single molecule PCR reactions in parallel to detect and quantify a minority of mutant sequences in a complex mixture of DNA . It enables direct counting of the number of copies of a target sequences present in the sample and the multiplex detection of several sequences including rare mutations and hypermethylated regions [4,5]. Newly developed optimized NGS strategies can now also reach relevant sensitivity and allow the screening of a wide range of mutations in circulating DNA .
We will illustrate how, by allowing non invasive highly sensitive and quantitative analysis of ctDNA within blood patient samples, these methods are used for follow-up of cancer progression and tumor response to treatment. We will present results of prospective clinical trials highlighting pertinence of these approaches in pancreatic , lung  and colon cancer.
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