title: Levels of plasma circulating cell free nuclear and mitochondrial DNA as potential biomarkers for breast tumors.
abstract: BACKGROUND
  With the aim to simplify cancer management, cancer research lately dedicated itself more and more to discover and develop non-invasive biomarkers. In this connection, circulating cell-free DNA (ccf DNA) seems to be a promising candidate. Altered levels of ccf nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) have been found in several cancer types and might have a diagnostic value.
  
  
  METHODS
  Using multiplex real-time PCR we investigated the levels of ccf nDNA and mtDNA in plasma samples from patients with malignant and benign breast tumors, and from healthy controls. To evaluate the applicability of plasma ccf nDNA and mtDNA as a biomarker for distinguishing between the three study-groups we performed ROC (Receiver Operating Characteristic) curve analysis. We also compared the levels of both species in the cancer group with clinicopathological parameters.
  
  
  RESULTS
  While the levels of ccf nDNA in the cancer group were significantly higher in comparison with the benign tumor group (P < 0.001) and the healthy control group (P < 0.001), the level of ccf mtDNA was found to be significantly lower in the two tumor-groups (benign: P < 0.001; malignant: P = 0.022). The level of ccf nDNA was also associated with tumor-size (<2 cm vs. >2 cm<5 cm; 2250 vs. 6658; Mann-Whitney-U-Test: P = 0.034). Using ROC curve analysis, we were able to distinguish between the breast cancer cases and the healthy controls using ccf nDNA as marker (cut-off: 1866 GE/ml; sensitivity: 81%; specificity: 69%; P < 0.001) and between the tumor group and the healthy controls using ccf mtDNA as marker (cut-off: 463282 GE/ml; sensitivity: 53%; specificity: 87%; P < 0.001).
  
  
  CONCLUSIONS
  Our data suggests that nuclear and mitochondrial ccf DNA have potential as biomarkers in breast tumor management. However, ccf nDNA shows greater promise regarding sensitivity and specificity.
authors.affiliation: Laboratory for Prenatal Medicine and Gynecologic Oncology, Women's Hospital/Department of Biomedicine, University of Basel, Switzerland.
authors.forename: Corina
authors.initials: C
authors.lastname: Kohler
authors.forename: Ramin
authors.initials: R
authors.lastname: Radpour
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Barekati
authors.forename: Reza
authors.initials: R
authors.lastname: Asadollahi
authors.forename: Johannes
authors.initials: J
authors.lastname: Bitzer
authors.forename: Edward
authors.initials: E
authors.lastname: Wight
authors.forename: Nicole
authors.initials: N
authors.lastname: Bürki
authors.forename: Claude
authors.initials: C
authors.lastname: Diesch
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Holzgreve
authors.forename: Xiao Yan
authors.initials: XY
authors.lastname: Zhong
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D016022:Case-Control Studies; D002467:Cell Nucleus / Q000235:genetics*; D002474:Cell-Free System; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000097:blood*; D003937:Diagnosis, Differential; D005260:Female; D006262:Health; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D009362:Neoplasm Metastasis; D012372:ROC Curve; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D004272:DNA, Mitochondrial; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human