title: Methodological, biological and clinical aspects of circulating free DNA in metastatic colorectal cancer.
abstract: BACKGROUND
  Circulating DNA can be used to measure the total cell-free DNA (cfDNA) and for detection and quantification of tumor-specific genetic alterations in the peripheral blood, and the broad clinical potential of circulating DNA has attracted increasing focus over the past decade. Concentrations of circulating DNA are high in metastatic colorectal cancer (CRC), and the total levels of cfDNA have been reported to hold strong prognostic value. Colorectal tumors are characterized by a high frequency of well known, clinically relevant genetic alteration, which is readily detected in the cfDNA and holds potential for tailoring of palliative therapy and for monitoring during treatment. This review aims to present the current literature which has specifically reported data on the potential utility of cfDNA and on tumor-specific mutations in metastatic colorectal cancer (mCRC).
  
  
  METHODS
  Methodological, biological and clinical aspects are discussed based on the most recent development in this specific setting, and eligible studies were identified by systematic literature searched from Pubmed and EMBASE in addition to conference papers and communications.
  
  
  RESULTS
  The literature regarding cfDNA in CRC is broad and heterogeneous concerning aims, nomenclature, methods, cohorts and clinical endpoints and consequently difficult to include in a single systematic search. However, the available data underline a strong clinical value of measuring both total cfDNA levels and tumor-specific mutations in the plasma of patients with mCRC, pre- and during systemic therapy.
  
  
  CONCLUSIONS
  This paper had gathered the most recent literature on several aspects of cfDNA in mCRC, including methodological, biological and clinical aspects, and discussed the large clinical potential in this specific setting, which needs to be validated in carefully designed prospective studies in statistically relevant cohorts.
authors.affiliation: a Department of Oncology , Aarhus University Hospital, Institute of Clinical Medicine, Aarhus University , Aarhus , Denmark.
authors.forename: Karen-Lise G
authors.initials: KG
authors.lastname: Spindler
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics / Q000556:secondary*; D004252:DNA Mutational Analysis / Q000379:methods*; D004273:DNA, Neoplasm / Q000097:blood* / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm