Free circulating nucleic acids in plasma and serum (CNAPS) - Useful for the detection of lung cancer patients?

Recent results indicate that not only intact circulating tumor cells but also extracellular, free-circulating nucleic acids containing tumor-associated genetic alterations can be detected in peripheral blood of cancer patients. The development of sensitive and specific methods for the detection of miniscule quantities of DNA or RNA has made it possible to isolate and characterize these tumor-associated alterations in cell-free circulating nucleic acids. So far almost all genetic alterations found in a tumor were also found in free-circulating nucleic acids, i.e. point mutations (like in p53, K-ras, myc, EGFR, etc.), microsatellite alterations, epigenetic alterations like hypermethylation of CpG islands in promotor regions and the overexpression of tumor-associated genes at the mRNA and the microRNA level. In this review we discuss the potential use of the detection and characterization of tumor-associated alterations in free-circulating nucleic acids for the differentiation between patients with benign lung diseases and lung cancer patients. In addition, we highlight some technical points considering the pre-analytical probe handling and assay standardization, as well as the biology behind free-circulating nucleic acids.