Bladder cancer is common in the United States and is bnmkjrelatively understudied relative to its public health implications. This project seeks to understand how the epigenetic silencing of apoptotic genes by abnormal methylation of cytosine residues occurs as a function of age and carcinogenesis. We have discovered that we can use the quantitative MethyLight high throughput platform to detect DNA methylation changes in urine sediments, which gives us unique opportunities to study cancer evolution and progression in a longitudinal fashion using a noninvasive sampling technique. We wish to take advantage of the availability of urine sediments to translate our basic science discoveries into strategies which can assist in the identification of recurrent tumors. Since recurrence is a common feature of superficial bladder cancer, the achievements of these goals would have profound impact on the patient's quality of life. To achieve these goals we will accomplish the following specific aims. First, we will complete the development of a marker panel of CpG islands located upstream and just downstream of the transcription start sites of apoptotic genes and verify that methylation observed in urine sediments corresponds with methylation in the primary tumors. Secondly, we will take advantage of the urine sediment system to ascertain how DNA methylation patterns evolve in the urinary bladder as a function of aging. Thirdly, we will conduct consecutive studies on patients who have been surgically treated for either superficial or invasive bladder cancer to determine whether the methylation patterns present at the time of initial surgical excision reappear in the urine sediments before the recurrent tumors can be detected by conventional means. Thus, the achievement of these three specific aims will allow us not only to understand the epigenetics of bladder cancer but also use these fundamental discoveries to better the lives of patients with this disease. ? ?
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