title: Circulating mitochondrial DNA in serum: a universal diagnostic biomarker for patients with urological malignancies.
abstract: OBJECTIVE
  Cell-free circulating mitochondrial DNA (mtDNA) has been proposed as universal diagnostic and prognostic biomarker in cancer patients.
  
  
  METHODS
  Cell-free DNA was isolated from 1 ml serum from patients with bladder cancer (BCA, n = 84), renal cell carcinoma (RCC, n = 33), and prostate cancer (CaP, n = 23), and compared with healthy individuals (n = 79). Quantitative real-time PCR was used to analyze the levels of a 79 bp (mtDNA-79), and 220 bp (mtDNA-220) fragment of the mitochondrial specific 16S-RNA. The mitochondrial DNA integrity (mtDNA-integrity) was defined as ratio of mtDNA-220 to mtDNA-79 fragments.
  
  
  RESULTS
  In healthy controls, mtDNA-79 levels were increased in male volunteers; mtDNA-230 levels and mtDNA-integrity were correlated with age. Neither mtDNA levels nor mtDNA-integrity were correlated with age or gender in cancer patients. Circulating mtDNA-79 (median 8.75 × 10(6) vs. 0.43 × 10(6) copies/ml) and mtDNA-230 (8.11 × 10(6) vs. 0.27 × 10(6) copies/ml) levels were significantly increased in cancer patients and allowed sensitive (84%) and specific (97%) discrimination from healthy controls. mtDNA levels were unequally distributed among the different cancer entities (mtDNA-79: BCA 9.54 × 10(6) vs. RCC 6.69 × 10(6) vs. CaP 4.48 × 10(6) copies/ml; mtDNA-230: BCA 9.78 × 10(6) vs. RCC 6.74 × 10(6) vs. CaP 1.94 × 10(6) copies/ml). The mtDNA-integrity was increased in RCC and BCA patients compared to control subjects and CaP patients. Serum mtDNA-integrity was correlated with pathological stage in RCC and with tumor grade in BCA patients.
  
  
  CONCLUSIONS
  Circulating mtDNA levels are associated with gender and age in healthy individuals, but not in cancer patients. Quantification of circulating mtDNA may help identify patients with urologic malignancies.
authors.affiliation: Klinik und Poliklinik für Urologie, Universitätsklinikum Bonn, Bonn, Germany. joerg.ellinger@ukb.uni-bonn.de
authors.forename: Jörg
authors.initials: J
authors.lastname: Ellinger
authors.forename: David C
authors.initials: DC
authors.lastname: Müller
authors.forename: Stefan C
authors.initials: SC
authors.lastname: Müller
authors.forename: Stefan
authors.initials: S
authors.lastname: Hauser
authors.forename: Lukas C
authors.initials: LC
authors.lastname: Heukamp
authors.forename: Alexander
authors.initials: A
authors.lastname: von Ruecker
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Bastian
authors.forename: Gisela
authors.initials: G
authors.lastname: Walgenbach-Brunagel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D004272:DNA, Mitochondrial / Q000097:blood*; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007680:Kidney Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D012737:Sex Factors; D001749:Urinary Bladder Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004272:DNA, Mitochondrial; D012336:RNA, Ribosomal, 16S