Applications of free circulating nucleic acids in clinical medicine: recent advances.

The objective of this review article was to highlight briefly the recent advances made relevant to applications of free circulating nucleic acids (FcNAs) in clinical medicine. Detection of FcNAs in plasma, serum and other body fluids from healthy subjects as well as in patients has opened up the possibility of diagnosis and monitoring of diseases. With the rapid developments in molecular biology techniques such as real-time quantitative polymerase chain reaction (rt-qPCR), quantitative methylation specific PCR (qMS-PCR), matrix-assisted laser desorption/ionization time of flight (MALDI-ToF) mass spectrometry, quantitative fluorescent PCR (QF-PCR), single allele primer extension reaction (SAPER) method and other techniques the applications in clinical medicine have increased. The recent discovery of epigenetic changes in placental/fetal DNA and the detection of fetal/placental-specific RNAs have made FcNAs to be used for diagnosis of genetic disorders in all pregnancies irrespective of the gender of the fetus in early intrauterine life. It is now possible to detect very small amounts of, and specific mutations in, fetal DNA in the presence of excess non-specific maternal DNA. In oncology, detection and monitoring of tumors are now possible by the detection of tumor-derived FcNAs. In other conditions, such as diabetes mellitus, trauma and stroke FcNAs have been shown to be useful also. In spite of these advances questions regarding the origin and biologic significance of FcNAs remain to be answered. Standardization of methodologies including pre-analytical and analytical aspects will revolutionize the applications of FcNAs in the diagnosis and monitoring of diseases in clinical medicine in the next few years.