Diagnostic developments involving cell-free (circulating) nucleic acids

Background: The detection of circulating nucleic acids has long been explored for the non-invasive diagnosis of a variety of clinical conditions. In earlier studies, detection of circulating DNA has been investigated for the detection of various forms of cancer. Metastasis and recurrence in certain cancer types have been associated with the presence of high levels of tumor-derived DNA in the circulation. In the case of pregnancies, detection of fetal DNA in maternal plasma is a useful tool for detecting and monitoring certain fetal diseases and pregnancy-associated complications. Similarly, levels of circulating DNA have been reported to be elevated in acute medical emergencies, including trauma and stroke, and have been explored as indicators of clinical severity. Apart from circulating DNA, much attention and effort have been put into the study of circulating RNA over the last few years. This area started from the detection of tumor-derived RNA in the plasma of cancer patients. Soon after that, detection of circulating fetal RNA in maternal plasma was described. Plasma RNA detection appears to be a promising approach for the development of gender- and polymorphism-independent fetal markers for prenatal diagnosis and monitoring. This development also opens up the possibility of non-invasive prenatal gene expression profiling by maternal blood analysis. Besides circulating DNA and RNA in plasma and serum, cell-free DNA in other body fluids, such as urine, has been detected in patients with different clinical conditions. Regardless of the sources of cell-free DNA for clinical use, the amount is frequently scarce. Methods: Technical advancements in detecting free DNA have been made over the years. Conclusions: It is likely that further developments in the field of circulating nucleic acids will provide us with new diagnostic and monitoring possibilities over the next few years. (c) 2005 Elsevier B.V. All rights reserved.