DNA alterations in body fluids as molecular tumor markers for urological malignancies

Objectives: DNA-based tumor markers are characterized by unique specificity rendering them an attractive target for molecular diagnosis of cancer in body fluids like blood serum/plasma and urine. Both cell-free tumor DNA circulating in plasma/serum and cellular tumor DNA are detectable by minimally invasive measures. Methods: Three main detection methods, microsatellite analysis, mutation analysis in genomic or mitochondrial DNA and gene promoter hypermethylation analysis are applied. Detection of gene promoter hypermethylation by methylation-specific PCR enables the best methodical sensitivity requiring a ratio of tumor DNA within normal DNA of less than 1: 1000. Results/Conclusions: Tumor DNA derived from renal cell carcinoma, bladder cancer or prostate cancer is detectable in considerably more than 50% of plasma/serum samples and more than 70% of urine samples from these patients. Because the targeted DNA alterations are absent or very rare in controls, the specificity of DNA-based tumor detection methods reaches almost 100%. Although the methodology currently is experimental, automatization will make it easier and less expensive. This review is focused on the potential clinical value of DNA-based analysis of body fluids for the initial diagnosis and the follow-up of urologic cancer patients. (C) 2002 Elsevier Science B.V. All rights reserved.