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Purpose: New methods to accurately predict an individual tumor behavior are urgently required to improve the treatment of cancer. We previously found that promoter hypermethylation can be an accurate predictor of bladder cancer progression, but it is not cancer specific. Here, we investigate a panel of methylated loci in a prospectively collected cohort of bladder tumors to determine whether hypermethylation has a useful role in the management of patients with bladder cancer.

Experimental Design: Quantitative methylation-specific PCR was done at 17 gene promoters, suspected to be associated with tumor progression, in 96 malignant and 30 normal urothelial samples. Statistical analysis and artificial intelligence techniques were used to interrogate the results.

Results: Using log-rank analysis, five loci were associated with progression to more advanced disease (RASSF1a, E …