title: Cell-free and cell-bound circulating nucleic acid complexes: mechanisms of generation, concentration and content.
abstract: BACKGROUND
  Extracellular nucleic acids are found in human blood and cell culture medium as cell-free or being adsorbed at cell surface. In the last years, the circulating extracellular nucleic acids in blood were shown to be associated with certain diseases. Attempts are made to develop non-invasive methods of early tumor diagnostics based on analysis of circulating DNA and RNA.
  
  
  METHODS
  This article reviews accumulating data regarding cell-free and cell-surface-bound extracellular nucleic acid nature and generation mechanisms. Their existence as a constituent of the naturally occurring complexes with proteins or membrane-bearing particles is discussed with regard to their homeostatic concentration and distribution in healthy donor blood which are significantly altered in cancer patients. Gene-target and whole-genome studies reveal significant differences in gene representation between extracellular DNA and genome DNA. Overrepresentation of regions with high transcription activity has led to proposal that extracellular DNA generation is strongly dependent on the parent genome functionality, which is associated with chromosome packaging and DNA methylation levels.
  
  
  CONCLUSIONS
  Recent studies provide evidence of the circulating nucleome organization complexity indicating that discovery of extracellular DNA generation and circulation patterns in healthy condition and cancer is essential to enable the development of proper approaches for the selection of valid diagnostic markers.
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 8, Acad. Lavrentyev Prosp., Novosibirsk, Russia. rykova@niboch.nsc.ru
authors.forename: Elena Y
authors.initials: EY
authors.lastname: Rykova
authors.forename: Evgeniy S
authors.initials: ES
authors.lastname: Morozkin
authors.forename: Anastasia A
authors.initials: AA
authors.lastname: Ponomaryova
authors.forename: Ekaterina M
authors.initials: EM
authors.lastname: Loseva
authors.forename: Ivan A
authors.initials: IA
authors.lastname: Zaporozhchenko
authors.forename: Nadezhda V
authors.initials: NV
authors.lastname: Cherdyntseva
authors.forename: Valentin V
authors.initials: VV
authors.lastname: Vlassov
authors.forename: Pavel P
authors.initials: PP
authors.lastname: Laktionov
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D002474:Cell-Free System; D044127:Epigenesis, Genetic; D006801:Humans; D009696:Nucleic Acids / Q000097:blood* / Q000378:metabolism
chemical_list: D009696:Nucleic Acids