HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data A correction has been published All Versions of this Article: clinchem.2008.108498v1 55/3/559    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Sunami, E. Articles by Hoon, D. S.B. Search for Related Content PubMed PubMed Citation Articles by Sunami, E. Articles by Hoon, D. S.B.

Multimarker Circulating DNA Assay for Assessing Blood of Prostate Cancer Patients

¹ Department of Molecular Oncology and ² the Breast and Endocrine Program, John Wayne Cancer Institute, Saint John’s Health Center, Santa Monica, CA; ³ Department of Medicine, Division of Oncology, University of Washington and Seattle Cancer Care Alliance, Seattle, WA; ⁴ Department of Radiation Oncology, Saint John’s Health Center, Santa Monica, CA; ⁵ The Angeles Clinic and Research Institute, Santa Monica, CA; ⁶ Pacific Cancer Center, Paragon, Singapore.

^aAddress correspondence to this author at: Department of Molecular Oncology, John Wayne Cancer Institute, 2200 Santa Monica Blvd., Santa Monica, CA 90404. Fax (310) 449-5282; e-mail hoon{at}jwci.org.

Background: Prostate cancer (PCa) detection using serum-based prostate specific antigen (PSA) is limited by frequent false-positive and -negative results. Genetic aberrations such as allelic imbalance (AI) and epigenetic changes such as promoter hypermethylation have been detected in circulating DNA of cancer patients. We hypothesized that circulating multimarker DNA assays detecting both genetic and epigenetic markers in serum would be useful in assessing PCa patients.

Methods: We assayed blood from healthy male donors (n = 40) and 83 patients with American Joint Cancer Committee (AJCC) stage I–IV PCa. DNA was assayed for AI of 6 genome microsatellites. We assessed methylation of RASSF1, RARB2, and GSTP1 using a methylation-specific PCR assay and analyzed the sensitivity of each assay for the detection of genetic or epigenetic changes in circulating DNA. The relation between circulating tumor-related DNA detection and prognostic factors was investigated.

Results: The proportion of patients demonstrating AI for 1 marker was 47% (38 of 81 patients). Methylation biomarkers were detected in 24 of 83 patients (28%). By combining 2 DNA assays, the number of PCa patients positive for 1 methylated or LOH marker increased (52 of 83; 63%). The combined assays detected PCa in 15 of 24 patients (63%) with normal PSA concentrations. The combination of the DNA assays detected the presence of PCa regardless of AJCC stage or PSA concentration. Combination of the DNA and PSA assays gave 89% sensitivity.

Conclusions: This pilot study demonstrates that the combined circulating DNA multimarker assay identifies patients with PCa and may yield information independent of AJCC stage or PSA concentration.

The following articles in journals at HighWire Press have cited this article:

				I. Lavon, M. Refael, B. Zelikovitch, E. Shalom, and T. Siegal Serum DNA can define tumor-specific genetic and epigenetic markers in gliomas of various grades Neuro Oncology, February 1, 2010; 12(2): 173 - 180. [Abstract] [Full Text] [PDF]