) Using a sensitive fluorescent quantitative-PCR (QPCR) energy-transfer assay, we can determine sequence copy number directly and efficiently. Application of this technology to cancer documents a surprisingly frequent assortment of copy number changes that are not seen in the stable normal genome. In preliminary studies, this technique was compared with standard loss of heterozygosity (LOH) techniques and found to be as accurate and more efficient in determining anomalies of bladder tumors. More recently, we have shown that this technology can be used to diagnose anomalies associated with bladder cancer in the abnormal genomes of tumor cells found in urine sediment and serum. Further, we have found that the absolute amount of DNA found assayed by QPCR in urine sediment is a marker for bladder abnormality. Putting all these techniques together, we propose an effort focused on bladder tumors to determine how QPCR can be used to diagnose and assist the therapy of bladder tumors. Since we have seen these genomic changes in a wide variety of tumors, the technology can ultimately be applied to all cancers. Questions to be addressed are: 1. Can a simplified variant of QPCR be used to screen efficiently for bladder tumors in urine sediment of populations at increased risk? 2. Can QPCR be used to diagnose and stage bladder tumors? 3. Can QPCR be used to monitor the therapy of bladder tumors when the bladder is left by monitoring urine sediment? 4. When the bladder is removed because of extensive disease, can QPCR be used to monitor the therapy of bladder tumors by monitoring serum? 5. Can QPCR be used to monitor the occurrence of metastatic disease by monitoring serum? Answering these questions will determine the roles that are appropriate for QPCR in the diagnosis and treatment of bladder tumors.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA078853-02
Application #
2896656
Study Section
Special Emphasis Panel (ZCA1-RLB-Y (M1))
Program Officer
Couch, Jennifer A
Project Start
1998-09-30
Project End
2002-07-31
Budget Start
1999-08-23
Budget End
2000-07-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Pediatrics
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Chiang, P W; Schneider, A; Borgnat, S et al. (2000) Molecular analysis of urine sediment for follow-up of urinary tract cancers. J Natl Cancer Inst 92:1779-80
Chiang, P W; Beer, D G; Wei, W L et al. (1999) Detection of erbB-2 amplifications in tumors and sera from esophageal carcinoma patients. Clin Cancer Res 5:1381-6