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Received on June 25, 2004
Accepted on October 20, 2004
Cancer Diagnostics |
1 Department of Surgery, University of Pittsburgh, Pittsburgh, PA
2 Biostatistics Facility, University of Pittsburgh Cancer Institute, Pittsburgh, PA, and Pittsburgh Cancer Institute and Hillman Cancer Center, Pittsburgh, PA
3 Department of Surgery, University of Pittsburgh, Pittsburgh, PA, and Pittsburgh Cancer Institute and Hillman Cancer Center, Pittsburgh, PA
* To whom correspondence should be addressed. E-mail: tony.godfrey{at}mssm.edu.
Background: Increased plasma DNA has been found in cancer patients and may have potential as a tumor marker. The objectives of this study were to develop a controlled, quantitative PCR (QPCR) assay to measure plasma DNA and then evaluate plasma DNA concentrations as a tumor marker in patients with thoracic malignancies.
Methods: We developed a QPCR assay for DNA, using the human 
-actin gene. Plasma samples were analyzed from 58 patients with esophageal cancer (EC; 20 banked samples and 38 prospectively collected samples) and 25 patients with lung cancer (LC; all prospectively collected). Control groups consisting of 51 patients with gastroesophageal reflux disease (GERD; 23 banked samples and 28 prospectively collected) and 11 healthy volunteers were also analyzed.
Results: The assay had an experimental variability <4%. In our banked samples, the mean concentration of plasma DNA in EC was 819.0 (range, 46.2-4738.0) µg/L vs 432.0 (6.0-2888.0) µg/L in GERD (P = 0.02). However, the prospectively collected samples had lower DNA concentrations, and there was no difference between cancer patients and controls. The mean DNA concentration was 10.6 µg/L (range, 7.0-14.0 µg/L) in healthy volunteers and 10.5 µg/L (range, 4.0-23.5 µg/L) in GERD controls vs 13.0 µg/L (range, 4.5-46.5 µg/L) in EC and 14.6 µg/L (range, 3.0-30.0 µg/L) in LC.
Conclusions: Our data indicate that plasma DNA concentrations are of limited diagnostic value when samples are prospectively collected and uniformly handled. This is in contrast to previously published results. Qualitative analysis of DNA may be needed if plasma nucleic acids are to be used as a diagnostic tool in cancer screening.
The following articles in journals at HighWire Press have cited this article:
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  K.-A. Yoon, S. Park, S. H. Lee, J. H. Kim, and J. S. Lee Comparison of Circulating Plasma DNA Levels between Lung Cancer Patients and Healthy Controls J. Mol. Diagn., May 1, 2009; 11(3): 182 - 185. [Abstract] [Full Text] [PDF]
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 S. Holdenrieder, J. von Pawel, E. Dankelmann, T. Duell, B. Faderl, A. Markus, M. Siakavara, H. Wagner, K. Feldmann, H. Hoffmann, et al. Nucleosomes, ProGRP, NSE, CYFRA 21-1, and CEA in Monitoring First-Line Chemotherapy of Small Cell Lung Cancer Clin. Cancer Res., December 1, 2008; 14(23): 7813 - 7821. [Abstract] [Full Text] [PDF]
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 C. Lofton-Day, F. Model, T. DeVos, R. Tetzner, J. Distler, M. Schuster, X. Song, R. Lesche, V. Liebenberg, M. Ebert, et al. DNA Methylation Biomarkers for Blood-Based Colorectal Cancer Screening Clin. Chem., February 1, 2008; 54(2): 414 - 423. [Abstract] [Full Text] [PDF]
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R. Salani, B. Davidson, M. Fiegl, C. Marth, E. Muller-Holzner, G. Gastl, H.-Y. Huang, J.-C. Hsiao, H.-S. Lin, T.-L. Wang, et al. Measurement of Cyclin E Genomic Copy Number and Strand Length in Cell-Free DNA Distinguish Malignant versus Benign Effusions Clin. Cancer Res., October 1, 2007; 13(19): 5805 - 5809. [Abstract] [Full Text] [PDF]
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 F. Banki, R. J. Mason, D. Oh, J. A. Hagen, S. R. DeMeester, J. C. Lipham, K. Tanaka, K. D. Danenberg, W. N. Yacoub, P. V. Danenberg, et al. Plasma DNA as a Molecular Marker for Completeness of Resection and Recurrent Disease in Patients With Esophageal Cancer Arch Surg, June 1, 2007; 142(6): 533 - 539. [Abstract] [Full Text] [PDF]
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A. K. Pathak, M. Bhutani, S. Kumar, A. Mohan, and R. Guleria Circulating Cell-Free DNA in Plasma/Serum of Lung Cancer Patients as a Potential Screening and Prognostic Tool Clin. Chem., October 1, 2006; 52(10): 1833 - 1842. [Abstract] [Full Text] [PDF]
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 N. Umetani, A. E. Giuliano, S. H. Hiramatsu, F. Amersi, T. Nakagawa, S. Martino, and D. S.B. Hoon Prediction of Breast Tumor Progression by Integrity of Free Circulating DNA in Serum J. Clin. Oncol., September 10, 2006; 24(26): 4270 - 4276. [Abstract] [Full Text] [PDF]
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N. Umetani, J. Kim, S. Hiramatsu, H. A. Reber, O. J. Hines, A. J. Bilchik, and D. S. B. Hoon Increased Integrity of Free Circulating DNA in Sera of Patients with Colorectal or Periampullary Cancer: Direct Quantitative PCR for ALU Repeats. Clin. Chem., June 1, 2006; 52(6): 1062 - 1069. [Abstract] [Full Text] [PDF]
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B. Schmidt, S. Weickmann, C. Witt, and M. Fleischhacker Improved Method for Isolating Cell-Free DNA Clin. Chem., August 1, 2005; 51(8): 1561 - 1563. [Full Text] [PDF]
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