Project Details
Description
Most neoplasms, including bladder cancer, are thought to progress through
a series of clinical histopathological stages. This progression is
accompanied by specific genetic changes which include activation of
protooncogenes and loss of tumor suppressor genes. Recently, we defined
two critical events that occur early in bladder progression: (1) a high
incidence of loss on chromosome 9p21 and less often (2) instability of
microsatellite repeats. A novel tumor suppressor gene, p16, is often
deleted in the 9p21 region. However, other areas of chromosomal deletion
and other critical genes in known regions of high frequency loss remain to
be identified. Studies in this proposal are aimed at the development of a
genetic model of bladder cancer progression and ultimately in developing
new molecular detection strategies. First, a variety of lesions including,
preinvasive and invasive tumor will be tested to identify new regions of
loss (and verify established regions of loss) and microsatellite
alterations to develop a molecular progression model for bladder cancer.
Second, mapping studies will continue to identify the precise location of
putative tumor suppressor gene loci on 14q and other chromosomal arms with
a high frequency of loss. Finally, we will continue development of assays
that can detect microsattelite alterations in urine. Initial feasibility
projects demonstrate that these studies will be greatly accelerated with
the advent of high throughput fluorescent capillary and chip arrays. A
combination of the above studies should provide important insight into the
specific genetic changes associated with bladder tumor progression and
eventually lead to the isolation of novel tumor suppressor genes.
Additionally, establishment of highly susceptible microsatellite repeats
in bladder tumors will allow identification of critical targets for
further development of molecular detection approaches.
Status | Finished |
---|---|
Effective start/end date | 1/1/01 → 7/31/11 |
ASJC
- Genetics
- Molecular Biology
- Oncology
- Cancer Research
- Cell Biology
- Statistics and Probability
- Statistics, Probability and Uncertainty
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