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Office: 803-434-1333
Lab: 803-434-2067
Fax: 803-434-3795
Cell: 803-466-7343
E-mail:
phillipb
@gw.med.sc.edu
Cancer
Genetics Lab
South Carolina Cancer Center
14 Richland Medical Park
Suite
500
Columbia, SC 29203 |
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The goal of our
laboratory is to elucidate the molecular events associated with the
progression of colon cancer, with particular focus on changes in gene
expression that occur during transitions between stages of significantly
different probabilities of good clinical outcome. Two such transitions are
of great interest, and the necessary reagents are now available to us for
study. First, we seek to identify alterations in gene expression that are
diagnostic for the transition from node-negative (T3N0M0) to node-positive
(T3N2M0), two states with very significantly different clinical courses and
treatment regimens. Once identified, these diagnostic genes will then be
assessed for their predictive value in a retrospective analysis of a large
set of tumors for which node status and outcome data is available. The gene
expression signature will allow for a rapid and more sensitive
identification of node-positive tumors, and elucidate the molecular
mechanism of the transition between these two clinically important
biological states. Second, we seek to identify alterations in gene
expression signature that accompany loss of heterozygosity along chromosomal
arms 8p and 18q, and to use this data to identify tumor suppressors located
in these regions. Patients with mismatch repair proficient tumors that have
retained both arms have a 100% 5-year survival rate, while those patients
with LOH at both locations have only a 40% 5-year survival rate. LOH at
these two locations is therefore a more accurate prognostic indicator than
is histopathologic grade. However, LOH is tedious and technically demanding,
and not practical for clinical deployment. Measurements of the expression
levels of a small, highly informative subset of genes is a reasonable
surrogate, and will allow for the identification of high-risk early stage
tumors for which adjuvant therapy should be indicated. SAGE is a method of
gene expression analysis that will allow the identification of unknown
genes. Our analysis of alterations in expression of tumors with and without
LOH may reveal unknown genes mapping to previously identified minimally lost
regions, which are candidate tumor suppressor genes to be evaluated for
mutations. |
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