CHROMOSOMES OF HUMAN BLADDER TUMORS

拟议研究的目的继续包括1) 进一步的初级(特定)染色体改变的建立 与我们和其他人已经描述的膀胱癌相似 (例如，5q-/-5、7、9q-/-9、11p-/illq)，2) 每个病例的细胞遗传学发现和一些参数 (组织学，包括分期和分级，标记状态，病程 疾病)上可能描绘出膀胱癌亚型 初级核型改变的基础，3)发展 利用重复序列的原位杂交技术的应用 测序探针用于识别至少部分 浅表性红斑狼疮间期核核型改变(如7、-9) 膀胱病变(例如，原位癌)，通常不能 细胞遗传学检查和4)膀胱的分子研究 与染色体改变有关的癌症，例如基因 修饰或改变基因表达。 进一步勾画原初生染色体变化的重点 会被放在获得膀胱癌的单一细胞遗传学上 异常或事件。由于似乎存在关联，因此 初级核型事件和预后(例如，相对较好 7分或-9分的肿瘤预后和预后不良 对于5q-、i5p或11p-)，这样的研究将不仅扩展到 已知的原始染色体改变的更大的肿瘤系列， 也适用于新建立的亚型。分子研究将 在描述浅表膀胱的特征方面尤为重要 细胞遗传学分析通常不成功的病变 其中，当前的复发或复发预测参数 侵入性是不可靠的。特别有希望的似乎是 用适当的探针进行原位杂交技术 间期核浅表或小病灶显示 -7、9等细胞遗传学改变(预后较好) 或Y丢失(预后不良)。

The aim of the proposed research continue to include 1) the establishment of further primary (specific) chromosome changes in bladder cancer akin to those already described by us and others (e.g., 5q-/-5, +7, 9q-/-9, 11p-/illq), 2) correlation of the cytogenetic findings with a number of parameters of each case (histology, including stage and grade, marker status, course of disease) to possibly delineate subtypes of bladder cancer on the basis of the primary karyotypic change, 3) to develop the application of in-situ hybridization techniques utilizing repeat sequenced probes for the recognition of at least some of the karyotypic changes (e.g., +7, -9) in interphase nuclei of superficial bladder lesions (e.g., carcinoma-in-situ) which often cannot be examined cytogenetically and 4) molecular studies of bladder cancer, as related to the chromosome changes, e.g., gene modification or altered gene expression. To further delineate primary chromosome changes much emphasis will be put on obtaining bladder cancers with a single cytogenetic anomaly or event. Since correlations appear to exist between the primary karyotypic event and prognosis (e.g., relatively good prognosis for tumors with +7 or -9 and poor prognosis for those with 5q-, i5p, or 11p-), such studies will be extended not only to larger series of tumors with known primary chromosome changes, but also to newly established subtypes. The molecular studies will be especially important in characterizing superficial bladder lesions in which cytogenetic analyses are usually not successful and in which current predictive parameters of recurrence or invasiveness are not reliable. Particularly promising appears to be in situ hybridization techniques with appropriate probes of interphase nuclei of superficial or small lesions to demonstrate such cytogenetic changes as -7 and +9 (relatively good prognosis) or loss of the Y (poor prognosis).