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，现在是第二大致癌原因 男性死亡人数。前列腺癌大致可分为三类 形式：潜伏性、侵袭性和转移性。这些表格中的每一个都可以是 病理上“分期”，与它们在或 超越前列腺及其分化程度(格里森的 等级)。因为肿瘤是由一系列染色体变化引起的 它允许细胞逃离控制细胞的正常机制 它的增长，那么这将是合乎逻辑的第一步 与肿瘤发展相关的特定染色体变化。 然而，关于遗传和分子的信息仍然很少。 导致前列腺癌的事件的演变。到目前为止， 大多数鉴定核型染色体重排的尝试是在 前列腺癌活检被证明是令人沮丧的。在某种程度上，这是 由于前列腺癌的细胞生长特性，它可以 在组织分裂前休眠几个月。除了它们缓慢的增长之外 从前列腺癌活检中获得中期分裂相的比率也有 选择快速生长的细胞的固有问题，偏向于 结果是可能不能代表肿瘤的细胞。因此， 以避免与传统细胞遗传学显带相关的问题 技术，我们打算应用荧光原位技术 杂交结合早熟的染色体凝集成核型 活检中的前列腺癌细胞。使用这种新方法，需要 甚至可以避免让细胞生长很短的时间，而且 要分析的细胞群仅受 活组织检查。这将允许直接对肿瘤细胞进行原位分析，这是一个目标 这是传统的细胞遗传学分析很难实现的，因为 对细胞培养获得中期染色体的要求 显带分析。我们将使用染色体特定的DNA文库作为 探测每个人类染色体的粗大结构异常的探针； 染色体特异性重复探针，如阿尔法卫星DNA (着丝粒特异探针)检测染色体数目的变化；以及 COSMID或YAC(酵母人工染色体)探针 被认为与前列腺癌有关的微染色体区域 癌症，如7q24和10q24，以及我们在 这项研究的进程。这项研究的最终目标是确定 具有阶段或分化特异性的染色体改变 前列腺癌。对于前列腺癌来说，这个目标还没有实现 癌症，主要是由于获取足够的材料来 细胞遗传学分析。此外，已知的细胞遗传学知识 前列腺癌的变化将对预后和 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.