DNA fragments in sera of patients with prostate cancer (PCA) are biomarkers of disease but primarily do not originate from tumor cells.

Cancer patients have increased levels of serum DNA fragments (SDF) compared to most patients with non-malignant disease and healthy individuals. In PCA, DNA hypermethylation is also frequently observed (>80%) at promoter CpG islands of GSTP1, PTGS2 and TIG1. Therefore we analysed hypermethylation of these genes in SDF from patients with PCA (n=168) and benign prostate hyperplasia (BPH; n=42) and controls (n=11) for information about the cellular origin of DNA. SDF concentrations and the hypermethylated fractions were analysed using a methylation-sensitive restriction enzyme based real-time PCR. SDF levels were significantly increased in PCA vs BPH vs controls (65 vs 20 vs 7 ng/mL; p<0.001). Hypermethylation of GSTP1, TIG1 or PTGS2 was more frequently detected in PCA than in BPH patients and controls (overall 47% vs 8% vs 0%; p<0.001), but did not exceed 10% of total DNA. SDF levels distinguished PCA from BPH patients with a sensitivity of 83% and specificity of 69%. The diagnostic significance of SDF was greater than that of hypermethylation data. In conjunction with SDF, hypermethylation numbers did not contribute any further information. Both SDF levels and the hypermethylation status were not correlated to advanced tumor stage or grade (p>0.05). In summary SDF is a promising diagnostic marker in PCA. It does not primarily originate from tumor cells but from apoptotic and necrotic cells surrounding the tumor. [ABSTRACT FROM AUTHOR]