Journal
UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
Volume 30, Issue 4, Pages 509-515Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.urolonc.2010.03.004
Keywords
Kidney cancer; Bladder cancer; Prostate cancer; Mitochondrial DNA; Cell-free DNA
Categories
Funding
- Deutsche Forschungsgemeinschaft [CRC832]
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Objective: Cell-free circulating mitochondrial DNA (mtDNA) has been proposed as universal diagnostic and prognostic biomarker in cancer patients. Patients and 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 x 10(6) vs. 0.43 x 10(6) copies/ml) and mtDNA-230 (8.11 x 10(6) vs. 0.27 x 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 x 10(6) vs. RCC 6.69 x 10(6) vs. CaP 4.48 x 10(6) copies/ml; mtDNA-230: BCA 9.78 x 10(6) vs. RCC 6.74 x 10(6) vs. CaP 1.94 x 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. Conclusion: 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. (C) 2012 Elsevier Inc. All rights reserved.
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