GENETIC LOCI ASSOCIATED WITH PROSTATE CANCER DEVELOPMENT

一些染色体区域的杂合性缺失和RB和 P53抑制基因已在人前列腺肿瘤中观察到。 然而，这些改变还没有得到足够好的定义， 将特定的染色体位点与前列腺恶性肿瘤联系起来。我们的目标是 鉴定与恶性表型相关的染色体位点 这为理解这种疾病的发生提供了遗传学基础， 这种疾病的临床表现。 我们将重点关注染色体 先前被确定为前列腺受累的候选区域 癌（8p，10q，10p，16q，Y）。 这将通过使用DNA 可用于这些染色体区域的探针和FIGE凝胶、Southern和 人前列腺肿瘤和正常前列腺及白细胞DNA的PCR分析 DNA. 这些研究将包括RB-1和P53基因的分析， DNA、RNA和蛋白质水平。 将努力展示 存在与前列腺相关的确定的染色体缺失 癌症和表征RB-1和P53抑制基因的缺陷 及其产品。 我们将扩展我们以前的研究， 通过检测前列腺肿瘤中Y编码基因的表达， 两个重要的调控基因ZFY和SRY在肿瘤中的表达， 正常组织 这将包括将基因表达与 临床参数和基因甲基化模式。 最后，分子 这些研究的数据将与种族信息相关联， 个体的年龄和肿瘤的临床表现。 这 努力方向是鉴定特定的遗传基因座， 作为标志物，并提供遗传基础， 在这种疾病中观察到的种族和年龄偏见， 区分局部和转移性疾病。 这些研究是第一次 定义与前列腺癌相关的染色体区域的步骤 并致力于确定参与遗传过程的特定基因位点， 疾病的发展。

Loss of heterozygosity for a number of chromosomal regions and the RB and P53 suppressor genes has been observed in human prostate tumors. However, these alterations are not yet sufficiently well defined to associate specific chromosomal loci with prostate malignancy. Our goal is to identify chromosomal loci associated with the malignant phenotype which provide a genetic basis for understanding the occurrence and clinical manifestations of this disease. We will focus on chromosomal regions previously identified as candidates for involvement in prostate cancer (8p, 10q, 10p, 16q, Y). This will be accomplished using DNA probes available for these chromosomal regions and FIGE gel, southern and PCR analysis of DNA from human prostate tumors and normal prostate or WBC DNA. These studies will include analysis of the RB-1 and P53 genes at the DNA, RNA and protein level. Efforts will be made to demonstrate the presence of defined chromosomal deletions associated with prostate cancers and to characterize defects in the RB-1 and P53 suppressor genes and their products. We will expand our previous studies on the altered expression of Y-encoded genes in prostate tumors by examining the expression of two important regulatory genes, ZFY and SRY, in tumor and normal tissues. This will include correlating gene expression with clinical parameters and gene methylation patterns. Finally, molecular data from these studies will be correlated with information on the race and age of individuals and the clinical behavior of the tumor. This effort is directed toward identifying specific genetic loci which can be used as markers for, and provide a genetic basis toward, understanding the ethnic and age bias observed in this disease, and that can distinguish localized from metastatic disease. These studies are a first step in defining the chromosomal regions associated with prostate cancer and toward identifying specific genetic loci which participate in the development of the disease.