A collaborative effort has been established at the Eastern Virginia Medical School between the departments of Urology, Pathology, Microbiology and the Genetics Program to examine cytogenetic changes in prostatic carcinomas. Patients who present with symptoms suggestive of cancer of the prostate undergo transurethral resection and a portion of the resected specimen is used to initiate a primary prostatic culture. Cells are grown for a minimal time in-vitro (ideally 7-10 days) until an adequate portion of the culture(s) can be blocked in metaphase and mitotic chromosomes obtained. Slides are prepared and chromosomes are G- and Q-banded and mitotic cells are analyzed and photographed. Data concerning chromosome numbers per cell and any deviations from a normal, diploid karyotype are recorded and compared to histopathological reports on the initial biopsy material. Three mitotic preparations have thus far been obtained, two of which have been confirmed to be carcinoma by pathological examination. One of these prostatic carcinomas, with moderately differentiated cells, had a diploid karyotype (2N=46) with no detectable chromosome changes. The other carcinoma, which was found to be at the advanced, undifferentiated stage, had a modal chromosome number of 84 (range 62-88) with multiple chromosomal rearrangements. The Y chromosome was absent in this sample and several marker chromosomes, including i(1q), appear to consistently be present. The research proposed is designed to expand the study of prostatic tissue to approximately fifty specimens in each of the first and subsequent years, with the goal of correlating chromosome changes to the clinical course of patients with prostatic cancer. Stage and grade of the cancer, previous therapeutic treatment and any metastasis will be considered in the cytogenetic evaluation. (If metastasis to other tissue is involved and obtainable, this will also be analyzed for chromosome changes.) Since cancer of the prostate is very common in the older male population, any correlation between chromosome changes and the progression of the cancer is likely to prove invaluable in the management and eventual understanding of this disease.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
3R01CA046269-03S1
Application #
3189488
Study Section
Special Emphasis Panel (SRC (48))
Project Start
1988-03-01
Project End
1991-12-15
Budget Start
1990-03-01
Budget End
1991-12-15
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Eastern Virginia Medical School
Department
Type
Schools of Medicine
DUNS #
City
Norfolk
State
VA
Country
United States
Zip Code
23501
Brothman, Arthur R; Swanson, Gregory; Maxwell, Teresa M et al. (2005) Global hypomethylation is common in prostate cancer cells: a quantitative predictor for clinical outcome? Cancer Genet Cytogenet 156:31-6
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; Cui, Jiang (2002) Methylation in gene promoters: assessment after laser capture microdissection. Methods Enzymol 356:343-51
Brothman, Arthur R (2002) Cytogenetics and molecular genetics of cancer of the prostate. Am J Med Genet 115:150-6
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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