GENETIC MARKERS OF BLADDER CANCER PROGRESSION

描述：目标是识别和验证肿瘤标志物， 膀胱癌患者的预后。肿瘤材料的分析将 确定每个肿瘤的遗传和表达改变， 这些变化与肿瘤分期，与其他临床特征， 肿瘤和患者的临床病程。高通量分析 使用由1 mb的人类BAC基因组探针组成的基因组载玻片阵列 基因表达阵列由超过7，000个人类cDNA组成 克隆，将应用于人膀胱肿瘤样品。肿瘤将被分组 以确定每组的相关基因组。这些 然后，基因组将用于在单独的组中测试预后效用 患者样本。具体目标是：目标1。基因突变在 膀胱癌进展。我们将检验肿瘤的通路 发展是由基因决定的。DNA拷贝数和RNA表达 将根据膀胱分期在肿瘤组中识别变化 肿瘤进展。A.低度浅表疾病（150 pTa肿瘤）。B。高 浅表疾病等级（100 pT 1肿瘤和50 pTis）。C.肌肉浸润性 疾病（150）肿瘤将用于识别遗传改变的模式 并且表达根据阶段而变化。D.浅表性间质改变 和浸润性癌症：合作者制备的肿瘤成纤维细胞（海沃德博士） 将用于确定肿瘤间质中改变的基因表达模式， （与远离肿瘤的成纤维细胞相比）。候选基因鉴定 然后将检验这些研究与肿瘤分期的关系。目标二。 遗传变异作为临床结果的预测因子。候选基因 将检测目标1中确定的改变与临床 结果。A.高危浅表肿瘤。我们将测试候选人的效用 基因标记将在不同的患者组中进行测试， 膀胱内注射卡介苗和吉西替宾治疗后的结果。A.高风险 肌肉浸润性肿瘤将在患有淋巴结转移的患者中检测分子标记物。 未接受进一步治疗的阳性肿瘤，以及单独的患者 组，作为对MVAC治疗的反应的标志物，以及作为对MVAC治疗的反应的标志物。 紫杉烷类C.候选标记物与组织阵列的确认。我们将使用 组织阵列，以验证目标1中确定并在 目标2A-B。

DESCRIPTION: The goal is to identify and validate tumor markers, which predict the outcome of patients with bladder cancer. Analyses of tumor material will be done to define genetic and expression alterations in each tumor, to associate these alterations with the tumor stage, with other clinical characteristics of the tumor, and with the patient's clinical course. High throughput analyses using genomic slide-based arrays comprised of human BAC genomic probes at 1 mb density, and gene expression arrays comprised of more than 7,000 human cDNA clones, will be applied to human bladder tumor samples. Tumor will be grouped by stage in order to identify correlated sets of genes for each group. These gene sets will then be used for testing of prognostic utility in separate sets of patient samples. The Specific Aims are: Aim 1. Genetic Alterations During Bladder Cancer Progression. We will test the hypothesis that pathways of tumor progression are genetically defined. DNA copy number and RNA expression alterations will be identified in groups of tumor according to stage of bladder tumor progression. A. Low Grade Superficial Disease (150 pTa tumors). B. High Grade Superficial Disease (100pT1 tumors and 50 pTis). C. Muscle Invasive Disease (150) tumors will be used to identify patterns of genetic alterations and expression changes according to stage. D. Stromal changes in superficial and invasive cancer: Tumor fibroblasts prepared by collaborators (Drs. Hayward) will be used to define altered gene expression patterns in the tumor stroma (compared to fibroblasts away from the tumor). Candidates genes identified in these studies will then be tested for association with tumor stage. Aim 2. Genetic Alterations as Predictors of Clinical Outcome. Candidate gene alterations identified in Aim 1 will be tested for association with clinical outcome. A. High risk superficial tumor. We will test the utility of candidate gene markers will be tested in separate patient groups for association with outcome after treatment with intravesicle BCG and Gemcitibine. A. High risk muscle invasive tumors. Molecular markers will be tested in patients with node positive tumors who receive no further treatment, and in separate patient groups, as markers of response to MVAC therapy, and as markers of response to taxanes. C. Validation of Candidate Markers with Tissue Arrays. We will use tissue arrays to validate markers which are identified in Aim 1 and tested in Aims 2A-B.