This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, B. G. Articles by Shih, I.-M. Search for Related Content PubMed PubMed Citation Articles by Wang, B. G. Articles by Shih, I.-M.

Increased Plasma DNA Integrity in Cancer Patients¹

Departments of Pathology [B. G. W., Y-C. C., K. K., C-C. C., R. R., L. J. S., D. W. C., I-M. S.], Epidemiology [H-Y. H.], and Gynecology and Obstetrics [R. E. B., I-M. S.], The Johns Hopkins Medical Institutions, Baltimore, Maryland 21231

Tumor-released DNA in blood represents a promising biomarker for cancer detection. It has been postulated that tumor necrosis causes release of DNA of varying sizes, which contrasts apoptosis in normal tissue that releases smaller and more uniform DNA fragments. To test the hypothesis that increased DNA integrity, i.e., a longer DNA strand, is a tumor-associated marker in plasma, we determined the genomic DNA integrity index in plasma DNA using real-time PCR assays. A DNA integrity index and DNA concentration in plasma were determined in 61 patients with gynecological and breast cancers and 65 female patients without neoplastic diseases. We found that the area under the receiver-operating characteristic curve for DNA integrity index was 0.911 for cancer versus nonneoplastic patients. Given 100% specificity, the highest sensitivity achieved in detecting the cancer group was 62% (95% confidence interval = 0.50–0.74) at the index cutoff of 0.59. Fifty percent of stage I cancers had a DNA integrity index above this cutoff. All 11 patients with benign adnexal masses that clinically can be confused with malignant gynecological neoplasms demonstrated DNA integrity index < 0.59. Our findings suggest that increased DNA integrity in plasma DNA is associated with cancer, and measurement of DNA integrity may provide a simple and inexpensive measure for cancer detection.

This article has been cited by other articles:

				K.C. A. Chan, S.-F. Leung, S.-W. Yeung, A. T.C. Chan, and Y.M. D. Lo Persistent Aberrations in Circulating DNA Integrity after Radiotherapy Are Associated with Poor Prognosis in Nasopharyngeal Carcinoma Patients Clin. Cancer Res., July 1, 2008; 14(13): 4141 - 4145. [Abstract] [Full Text] [PDF]

				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]

				F. Wang, L. Wang, C. Briggs, E. Sicinska, S. M. Gaston, H. Mamon, M. H. Kulke, R. Zamponi, M. Loda, E. Maher, et al. DNA Degradation Test Predicts Success in Whole-Genome Amplification from Diverse Clinical Samples J. Mol. Diagn., September 1, 2007; 9(4): 441 - 451. [Abstract] [Full Text] [PDF]

				N. Mehra, M. Penning, J. Maas, N. van Daal, R. H. Giles, and E. E. Voest Circulating Mitochondrial Nucleic Acids Have Prognostic Value for Survival in Patients with Advanced Prostate Cancer Clin. Cancer Res., January 15, 2007; 13(2): 421 - 426. [Abstract] [Full Text] [PDF]

				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]

				R. Hanley, K. M. Rieger-Christ, D. Canes, N. R. Emara, A. P. Shuber, K. A. Boynton, J. A. Libertino, and I. C. Summerhayes DNA Integrity Assay: A Plasma-Based Screening Tool for the Detection of Prostate Cancer Clin. Cancer Res., August 1, 2006; 12(15): 4569 - 4574. [Abstract] [Full Text] [PDF]

				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]

				Y. Li, D. Elashoff, M. Oh, U. Sinha, M. A.R. St John, X. Zhou, E. Abemayor, and D. T. Wong Serum Circulating Human mRNA Profiling and Its Utility for Oral Cancer Detection J. Clin. Oncol., April 10, 2006; 24(11): 1754 - 1760. [Abstract] [Full Text] [PDF]

				J. Li, L. Harris, H. Mamon, M. H. Kulke, W.-H. Liu, P. Zhu, and G. Mike Makrigiorgos Whole Genome Amplification of Plasma-Circulating DNA Enables Expanded Screening for Allelic Imbalance in Plasma J. Mol. Diagn., February 1, 2006; 8(1): 22 - 30. [Abstract] [Full Text] [PDF]

				K.C. A. Chan, S.-W. Yeung, W.-B. Lui, T. H. Rainer, and Y.M. D. Lo Effects of Preanalytical Factors on the Molecular Size of Cell-Free DNA in Blood Clin. Chem., April 1, 2005; 51(4): 781 - 784. [Full Text] [PDF]