MOLECULAR CYTOGENETICS OF PROSTATE CANCER

前列腺癌的发病率正在迅速超过所有其他癌症 在50岁及以上的男性中，它现在是癌症的第二大原因。 男人的死亡 前列腺癌可以大致分为三种 形式：潜伏性、侵袭性和转移性。 每种形式都可以是 在病理学上“分期”，相对于它们的解剖位置， 除了前列腺及其分化程度（Gleason's 等级）。 因为肿瘤是由一系列染色体变异引起的 使细胞脱离正常机制， 它的增长，那么它将是一个合乎逻辑的第一步，以确定 与肿瘤发展相关的特定染色体变化。 然而，缺乏关于遗传和分子生物学的信息。 导致前列腺癌的事件的演变。 到目前为止， 大多数鉴定染色体核型重排的尝试， 前列腺癌活检已经证明是令人沮丧的。 这部分是 由于前列腺癌的细胞生长特征， 在分裂前潜伏数月 除了生长缓慢之外， 率，从前列腺癌活检中获得中期细胞也具有 选择快速生长细胞的固有问题， 结果可能不代表肿瘤的细胞。 因此，我们认为， 为了避免与常规细胞遗传学带型相关的问题 技术，我们打算应用荧光原位技术， 杂交联合收割机结合早熟染色体凝聚核型 前列腺癌细胞。 通过这种新方法， 甚至可以避免短时间的细胞生长， 待分析的细胞群仅受细胞大小的限制。 活检 这将允许直接原位分析肿瘤细胞， 这很难通过常规细胞遗传学分析实现，因为 细胞培养获得中期染色体的要求， 带型分析 我们将使用染色体特异性DNA文库， 用于检测每个人类染色体的总体结构畸变的探针; 染色体特异性重复探针如α卫星DNA （着丝粒特异性探针）以检测染色体数目变化;以及 粘粒或YAC（酵母人工染色体）探针， 微染色体区域与前列腺有关 癌症，如7 q24和10 q24，以及那些我们将发现在 在这项研究的过程中。 本研究的最终目的是确定 染色体改变是阶段或分化特异性的， 前列腺癌 前列腺尚未实现这一目标 癌症，主要是由于获得足够的材料， 细胞遗传学分析 此外，已知的细胞遗传学知识 前列腺癌的变化将有助于预后， 微小残留病的检测。

The incidence of prostate cancer is rapidly overcoming all other cancers in men 50 years and older and is now the second leading cause of cancer deaths in men. Prostate cancer can be broadly classified into three forms: latent, aggressive and metastatic. Each of these forms can be pathologically "staged" with respect to their anatomical location in or beyond the prostate and their degree of differentiation (Gleason's grade). Since a tumor results from a series of chromosomal alterations which allow the cell to escape from the normal mechanisms which control its growth, then it would be a logical first step to identify the specific chromosomal changes which are associated with tumor development. However, a paucity of information exists on the genetic and molecular evolution of events which are responsible for prostate cancer. To date, most attempts at identifying karyotypic chromosomal rearrangements in prostate cancer biopsies have proven to be frustrating. In part this is due to the cellular growth characteristics of prostate cancers which can lie dormant for months before division. In addition to their slow growth rate, obtaining metaphases from prostate cancer biopsies also has the inherent problem of selection for rapidly growing cells, biasing the results to cells that may not be representative of the tumor. Therefore, to avoid the problems associated with conventional cytogenetic banding techniques, we intend to apply the techniques of fluorescent in situ hybridization combine with premature chromosome condensation to karyotype prostate cancer cells from biopsies. With this new approach, the need to grow cells for even short periods of time can be avoided, and the population of cells to be analyzed is only limited by the size of the biopsy. this will allow direct analysis of tumor cells in situ, a goal that is difficult to achieve by conventional cytogenetic analysis because of the requirement for cell cultures to obtain metaphase chromosomes for banding analysis. We will use chromosome specific DNA libraries as probes to detect gross structural aberrations for each human chromosome; chromosome specific repetitive probes such as alpha satellite DNA (centromere specific probes) to detect numerical chromosome changes; and cosmid or YAC (Yeast Artificial Chromosomes) probes specific for microchromosomal regions that have putatively been implicated in prostate cancer such as 7q24 and 10q24 as well as those we will find during the course of this study. The ultimate goal of this study is to identify chromosome alterations which are stage or differentiation specific for prostate cancer. This goal has not yet been achieved for prostate cancer, mainly due to the problems of obtaining sufficient material for cytogenetic analysis. In addition, knowledge of known cytogenetic changes in prostate cancers will be useful both for prognosis and detection of minimal residual disease.