Serum Genetic Markers as Surrogates of Prostate Cancer Progression

As proposed, we have successfully established assays to detect free tumor-related DNA markers in serum of prostate cancer PCa patients and studied the potential use of the biomarker detection as surrogate genetic markers in monitoring PCa patients. Despite slight delay in the beginning, the program has moved expediently over the years from assay development and optimization to subject sample accrual and assessment. DNA markers involving allelic instability Al 6 markers and methylation of genes 3 markers with high specificity and sensitivity were screened and established. Of the 83 AJCC stage I-IV PCa patients studied, the proportion of patients demonstrating Al for greater or equal to 1 marker was 47 3881 patients. Methylation biomarkers were detected in 2483 28 patients. By combining two DNA assays, the number of PCa patients positive for greater or equal to 1 methylated or Al marker increased to 5283 63. The combined assays detected PCa in 15 of 24 63 patients with normal PSA levels. The combination of the DNA biomarker assays detected the presence of PCa regardless of AJCC stage of PSA level. The results obtained through this award demonstrate that tumor-related DNA marker serum assay may be used, independent of AJCC stage or PSA level, in identifying and monitoring patients with PCa.