A continuation of the previous study, """"""""Cytogenetic analysis of cells derived from prostatic carcinomas"""""""" is proposed. Expansion of the earlier work to include a greater number of prostatic tumors and a more comprehensive analysis is described. The study is designed to extend the cytogenetic analysis of prostate cancer to include nonradioactive in-situ hybridization with chromosome-specific probes; this will allow for analysis of interphase cells in addition to metaphase cells for gains or losses of specific chromosomal loci. Aneuploidy will be detected by evaluation of differences in the number of signals in interphase nuclei from prostate cancer specimens compared to normal diploid, controls. The strategy will also employ the use of fresh-fixed primary prostatic tissue, in an attempt to detect aneuploidies directly in tissue where metaphase cells are absent. The inclusion of in-situ hybridization methods has demonstrated increased sensitivity of analysis over classical cytogenetics as shown in the preliminary results of this proposal. In addition, the proposed work is designed to evaluate molecular changes in prostatic cancer. This will be accomplished by allelotyping of DNA isolated from tumors in comparison to adjacent normal tissue or peripheral blood using probes for variable numbers of tandem repeats (VNTRs) as well as screening for a number of oncogene rearrangements, amplifications and mutations. Initial chromosomal loci to be evaluated are based on previous work and a literature survey conducted by this laboratory. Chromosomes 1,2,5,7,10,14,20,22 and Y were determined to be involved in some prostatic tumors from that survey. While 23 of 77 primary prostate tumors (30%) were found in the previous study to contain aberrant clones, it is anticipated that this frequency may increase with the greater sensitivity described in this proposal. We have already detected statistical loss of either chromosomes 7, 10 or 16 in five prostate tumors using interphase in-situ hybridization. Further biological characterization of any primary prostatic cell lines, like the one isolated during the previous study (PPC-1) will be continued. Prostatic carcinoma is the most common cancer affecting U.S. males, with greater than 120,000 new cases expected in 1991. This study is designed to take a thorough, systematic approach to examine the etiology of this disease, and through the collaborative efforts between both basic science and clinical departments, the aim is to correlate chromosomal and/or DNA changes with stage and grade of the cancer.
Showing the most recent 10 out of 31 publications
