The objective of this study is to identify specific genetic changes which have prognostic significance in human bladder cancer. Several nonrandom chromosome changes have been described in transitional cell carcinoma of the bladder (TCCB). Specifically, several subgroups of TCCB have been proposed, each with a specific chromosome rearrangement. At the molecular level, specific genetic deletions have been documented. The clinical significance (diagnosis and prognosis) of genetic alterations has been well established for hematologic malignancies and some solid tumors. We hypothesize that nonrandom genetic alterations, chromosomal rearrangements and genetic deletions, have prognostic value in TCBB. In order to test this hypothesis, we will address the following specific hypotheses #1: There exists a critical segment or smallest region of overlap in all the nonrandom chromosomal changes in TCCB. #2: Most of the nonrandom genetic alterations in TCCB are unbalanced (deletions or duplications). #3: TCCBs show loss of heterozygosity for specific alleles at one or more of the same chromosomal regions such as 13q14, 17p12 etc., which are involved in the tumorigenesis of pediatric and common adult tumors. #4: Nonrandom genetic alterations such as deletion of 11p15, trisomy 7, duplication of 3p which are detected either by """"""""allelotyping"""""""" or cytogenetic methods can predict recurrence, tumor progression, and survival.
For aim #1, we will karyotype 300 tumors from newly diagnosed bladder cancer patients.
In aim #2 -3, we will, by the use of molecular methods, either confirm the cytogenetic changes or establish changes undetected by cytogenetic methods. For a subset of 45 cases, the extent of loss of heterozygosity will be evaluated by """"""""allelotyping"""""""".
In aim #4, we will do multivariate analysis to determine which genetic markers have prognostic value.
