Quantitation of cell-free DNA and RNA in plasma during tumor progression in rats

Dolores C García-Olmo,Inmaculada Toboso,María G Picazo,Damián García-Olmo,Ana I Asensio

doi:10.1186/1476-4598-12-8

Dolores C García-Olmo, Inmaculada Toboso + Show 3 more

Open Access

https://doi.org/10.1186/1476-4598-12-8

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Abstract

BackgroundTo clarify the implications of cell-free nucleic acids (cfNA) in the plasma in neoplastic disease, it is necessary to determine the kinetics of their release into the circulation.MethodsTo quantify non-tumor and tumor DNA and RNA in the plasma of tumor-bearing rats and to correlate such levels with tumor progression, we injected DHD/K12-PROb colon cancer cells subcutaneously into syngenic BD-IX rats. Rats were sacrificed and their plasma was analyzed from the first to the eleventh week after inoculation.ResultsThe release of large amounts of non-tumor DNA into plasma was related to tumor development from its early stages. Tumor-specific DNA was detected in 33% of tumor-bearing rats, starting from the first week after inoculation and at an increasing frequency thereafter. Animals that were positive for tumor DNA in the plasma had larger tumors than those that were negative (p = 0.0006). However, the appearance of both mutated and non-mutated DNA fluctuated with time and levels of both were scattered among individuals in each group. The release of non-tumor mRNA was unaffected by tumor progression and we did not detect mutated RNA sequences in any animals.ConclusionsThe release of normal and tumor cfDNA into plasma appeared to be related to individual-specific factors. The contribution of tumor DNA to the elevated levels of plasma DNA was intermittent. The release of RNA into plasma during cancer progression appeared to be an even more selective and elusive phenomenon than that of DNA.

Highlights

The presence of large quantities of cell-free nucleic acids in the serum and plasma of cancer patients was first reported several decades ago and was later verified for a variety of tumors
Release of cell-free nucleic acids (cfNA) from tumors might be directly involved in the development of metastases, as proposed in the “Genometastasis Hypothesis” [30,33], and it has been reported that plasma DNA can, transfect and oncogenically transform cultured cells [34]
The results of the present study suggest that the contribution of tumor DNA to the increased concentrations of plasma DNA in cancer patients might be intermittent, and, that DNA derived from normal and tumor cells might behave differently in terms, for example, of susceptibility to degradation

Summary

Introduction

The presence of large quantities of cell-free nucleic acids (cfNA) in the serum and plasma of cancer patients was first reported several decades ago and was later verified for a variety of tumors (for review, see ref. [1]). The presence of large quantities of cell-free nucleic acids (cfNA) in the serum and plasma of cancer patients was first reported several decades ago and was later verified for a variety of tumors The presence of cfNA in plasma has been analyzed for its potential prognostic value in the diagnosis and management of cancer Analyses have been based on both qualitative and quantitative investigations of cfNA and, in particular, of cell-free DNA (cfDNA). In spite of many apparently encouraging reports, the analysis of cfNA in plasma has not yet been translated into clinical practice. To clarify the implications of cell-free nucleic acids (cfNA) in the plasma in neoplastic disease, it is necessary to determine the kinetics of their release into the circulation

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