Circulating nucleic acids - a new universe for laboratory diagnostics

Circulating cell-free nucleic acids (cfNA, mostly referred to as cfDNA) are increasingly being recognized as a promising new substrate for clinical laboratory diagnostics. DNA, mRNA and miRNA are less likely to circulate in the peripheral blood in a "free naked" form, but rather as a packaged form and thus are fairly protected from degradation. Together with the fact that both qualities and quantities of cfNA vary in a number of important human disorders, this may create an entirely new universe for laboratory diagnostics. First applications enter the arena of routine diagnostic health care, e.g. the sensitive and highly specific detection of tumor mutations that will allow for a molecular profiling of tumor relapse or therapy failure (the so-called "liquid biopsy"). Still, many open questions require resolution including their cross validation with established and important routine biomarkers in the health care lab. Furthermore, critical preanalytical questions, analytical validity and precision need to be addressed to secure the quality of the material analyzed and meaningful results, respectively. Last but not least, circulating nucleic acids uncover a whole new biology of signals traveling through our bodies under various conditions of health and disease. It will be of great scientific importance to understand their biochemical and pathobiochemical implications. It is significant for both the development and implementation of this new diagnostic field that clinical chemistry can provide the required expertise in all these areas, thus ensuring rapid transition of cfNA into clinical medicine. It will complement the plethora of established diagnostic biomarkers that are provided every day to support clinical decisions for the benefit of the patient.