Study of circulating DNA structures and origins


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Zahra Al Amir Dache1,Amaelle Otandault1,Corinne Prevostel1,Alain Thierry1
1Institut de recherche en cancérologie de montpellier

Abstract

Background

Circulating free DNA (cfDNA) is composed of cell-free and particle associated DNA fragments that are found in the physiological circulating fluids of healthy and diseased human. Multiple studies had ignited the quantitative and the qualitative potential of cfDNA as a suitable biomarker for a non-invasive diagnosis, prognosis and therapeutic monitoring especially in oncology. Despite the promising future of cfDNA in clinical applications, the knowledge regarding its origins, compositions and functions is still lacking. Hence, the intent of the present study is to elucidate the various sources from which DNA could be released into circulation, and to better understand the biological properties of cfDNA molecules. In fact, cfDNA is derived not only from genomic DNA but also from extrachromosomal mitochondrial DNA. Moreover, it is evident that at least a portion of DNA enters into the bloodstream after cell death whether by necrosis or apoptosis, or following active secretion by viable cells. Those mechanisms goes hand in hand with the structural characterization of cfDNA.

Method

In order to identify and differentiate the different structure of cfDNA, we performed a study on plasma samples from healthy individuals and cancer patients, using a variety of techniques. In vitro experiments were carried out on extracellular DNA released by different cell lines.

Results

We characterized structures of different features providing optimal cfDNA detection.

Conclusion

This project is essential to expand our knowledge towards clinical implementation of cfDNA analysis and to elucidate its functional aspects especially in immunology.