This is the second revision of a competing continuation of the molecular and cytogenetic study of prostate cancer. The principal investigator has examined more than 250 primary prostate tumors and has shown that when using a collagen-based culture system and single-copy interphase FISH, prostate tumors frequently demonstrate chromosomal changes. Chromosome 17 loss is frequent and the PI has shown LOH in 17q. In addition, data has been accumulated implicating 8p and 10q in prostate cancer as well.
Four specific aims are proposed. The first will consist of continued collection and culture of prostate tumor specimens for study. It is anticipated that approximately 50 specimens of various grades will be available each year.
The second aim will be to perform single-copy FISH with selected P1 clones on interphase nuclei to screen for deletions. Both primary and archival samples will be utilized and initial probes will focus on 8p, 10q and 17q. Samples with regions of deletion will be further characterized by PCR and shared with a significant group of collaborators for additional analysis. The third specific aim will be to evaluate, by microcell-mediated chromosome transfer into prostate cancer cells, regions identified in the previous specific aims (or through the literature) for tumor suppressor activity. The final specific aim will examine the clinical correlation with the data obtained above with various clinical parameters such as tumor stage, grade, race, etc. It is hoped that these studies will lead to both the ultimate identification of tumor suppressor genes in prostate cancer as well as FISH prognostic tests.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA046269-12
Application #
6172144
Study Section
Mammalian Genetics Study Section (MGN)
Program Officer
Tricoli, James
Project Start
1988-03-01
Project End
2003-05-31
Budget Start
2000-06-01
Budget End
2003-05-31
Support Year
12
Fiscal Year
2000
Total Cost
$319,908
Indirect Cost
Name
University of Utah
Department
Pediatrics
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
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Neuhausen, Susan L; Slattery, Martha L; Garner, Chad P et al. (2005) Prostate cancer risk and IRS1, IRS2, IGF1, and INS polymorphisms: strong association of IRS1 G972R variant and cancer risk. Prostate 64:168-74
Pettus, Joseph A; Cowley, Brett C; Maxwell, Teresa et al. (2004) Multiple abnormalities detected by dye reversal genomic microarrays in prostate cancer: a much greater sensitivity than conventional cytogenetics. Cancer Genet Cytogenet 154:110-8
Zhou, Holly; Randall, R Lor; Brothman, Arthur R et al. (2003) Her-2/neu expression in osteosarcoma increases risk of lung metastasis and can be associated with gene amplification. J Pediatr Hematol Oncol 25:27-32
Brothman, Arthur R (2002) Cytogenetics and molecular genetics of cancer of the prostate. Am J Med Genet 115:150-6
Brothman, Arthur R; Cui, Jiang (2002) Methylation in gene promoters: assessment after laser capture microdissection. Methods Enzymol 356:343-51
Cui, J; Rohr, L R; Swanson, G et al. (2001) Hypermethylation of the caveolin-1 gene promoter in prostate cancer. Prostate 46:249-56
Dai, Q; Deubler, D A; Maxwell, T M et al. (2001) A common deletion at chromosomal region 17q21 in sporadic prostate tumors distal to BRCA1. Genomics 71:324-9
Verhagen, P C; Zhu, X L; Rohr, L R et al. (2000) Microdissection, DOP-PCR, and comparative genomic hybridization of paraffin-embedded familial prostate cancers. Cancer Genet Cytogenet 122:43-8
Brothman, A R; Maxwell, T M; Cui, J et al. (1999) Chromosomal clues to the development of prostate tumors. Prostate 38:303-12

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