Dysfunctional genes and aberrant expression of regulatory genes are speculated to be key events in human tumorigenesis. In prostate cancer, unlike many other types of cancer, few consiSuitent genetic alterations are detected. Frequently, genetic alterations including deletions and amplifications of certain chromosomal regions are found. Other undefined oncogenes and tumor suppressor genes may also play a role in prostate cancer development. We propose to detect somatic genetic alterations in prostate cancer and prostate metastases through the technique of PCR- based DNA fingerprinting. In this procedure, a single primer with an arbitrarily determined sequence is used to produce "fingerprint" of DNAs from normal and prostate tumor and metastases from the same donor. Since DNA sequences are often lost and/or amplified in prostate cancer, the fingerprints of prostate tumors and metastases should have different band(s) when compared to the fingerprints of the corresponding normal tissue of the same individual. Somatic genetic alterations such as losses of heterozygosity and chromosomal gains, two alterations frequently involved in the development of aneuploidy of cancer cells, can be detected by this very powerful technique. This proposal sets groundwork for Phase II identification of gene(s) involved in malignant progression and metastasis of prostate cancer.National Cancer Institute (NCI)
