GENETIC LOCI ASSOCIATED WITH PROSTATE CANCER DEVELOPMENT

一些染色体区域和Rb和Rb的杂合性丢失 在人类前列腺癌中已观察到P53抑制基因。 然而，这些变化还没有足够好的定义来 将特定的染色体基因与前列腺癌联系起来。我们的目标是 确定与恶性表型相关的染色体基因座 为理解这种现象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 以前被确定为参与前列腺癌的候选区域 癌症(8P、10Q、10P、16Q、Y)。这将使用DNA来完成 可用于这些染色体区域和无花果凝胶、Southern和 人前列腺肿瘤及正常前列腺或白细胞DNA的聚合酶链式反应分析 DNA这些研究将包括对Rb-1和P53基因的分析 DNA、RNA和蛋白质水平。将努力证明 存在与前列腺癌相关的明确的染色体缺失 肿瘤和Rb-1和P53抑制基因缺陷的特征 以及他们的产品。我们将扩大我们以前对改变的研究 检测Y编码基因在前列腺癌中的表达 两个重要的调控基因ZFY和SRY在肿瘤和肿瘤中的表达 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关于比赛的信息相关联 以及个体的年龄和肿瘤的临床行为。这 努力的方向是识别特定的遗传基因座，这些基因座可能是 用作理解的标记，并为理解提供遗传基础 在这种疾病中观察到的种族和年龄偏见，这可能 区分局限性和转移性疾病。这些研究是第一次 确定与前列腺癌相关的染色体区域的步骤 并致力于识别参与基因突变的特定基因座 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.