GENETIC MARKERS OF BLADDER CANCER PROGRESSION

描述：目标是识别和验证肿瘤标志物，这些标志物可以预测 膀胱癌患者的预后。将对肿瘤材料进行分析 定义每个肿瘤中的基因和表达变化，以将 这些改变与肿瘤分期、其他临床特征有关 肿瘤，以及患者的临床病程。高吞吐量分析 使用由1mb的人BAC基因组探针组成的基因组载玻片阵列 密度，以及由超过7,000个人cDNA组成的基因表达阵列 克隆，将应用于人膀胱癌样本。肿瘤将被分组 按阶段进行，以便确定每组相关的基因组。这些 然后，基因集合将被用于在不同集合中测试预后效用 病人样本的数量。具体目标是：目标1.基因改变 膀胱癌进展。我们将检验这样一种假设，即肿瘤的通路 进展是由基因定义的。DNA拷贝数与RNA表达 肿瘤的改变将根据膀胱的分期进行分组。 肿瘤进展。A.低级别浅表疾病(150个PTA肿瘤)。B.高 浅表疾病分级(肿瘤100pT1，PTI 50例)。C.肌肉侵袭性 疾病(150)肿瘤将用于识别基因改变的模式 表情随着阶段的不同而变化。D.浅表性间质改变 和浸润性癌症：合作者准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)。候选基因在 然后，这些研究将被测试与肿瘤分期的相关性。目标2. 基因改变可作为临床结果的预测因子。候选基因 AIM 1中确定的变化将进行测试，以与临床相关 结果。A.高危浅表肿瘤。我们将测试候选人的实用性 基因标记将在不同的患者组中进行测试，以确定与 卡介苗和吉西替宾囊内治疗的结果。A.高风险 肌肉侵袭性肿瘤。分子标志物将在结节患者中进行检测 未接受进一步治疗的阳性肿瘤，以及单独的患者 组，作为MVAC治疗反应的标志，以及作为对MVAC治疗反应的标志 紫杉烷。C.利用组织阵列对候选标记进行验证。我们将使用 组织阵列，用于验证在AIM 1中识别并在 目标2 A-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.