GENETIC MARKERS OF BLADDER CANCER PROGRESSION

膀胱癌进展的遗传标志物

• 批准号: 6744430
• 负责人: Frederic M. Waldman
• 金额: $ 26.17万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-05 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6744430
• 关键词: bladder neoplasm; clinical research; complementary DNA; diagnosis design /evaluation; fibroblasts; gemcitabine; genetic markers; human subject; lymph node neoplasm; muscle neoplasms; neoplasm /cancer chemotherapy; neoplasm /cancer diagnosis; neoplasm /cancer genetics; neoplastic process; outcomes research

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.

描述：目标是识别和验证肿瘤标志物，这些标志物可以预测 膀胱癌患者的结果。肿瘤材料的分析将是 完成定义每个肿瘤的遗传和表达改变，以关联 这些变化与肿瘤分期以及其他临床特征有关 肿瘤以及患者的临床病程。高通量分析 使用由 1 mb 人类 BAC 基因组探针组成的基于基因组玻片的阵列 密度和由 7,000 多个人类 cDNA 组成的基因表达阵列 克隆，将应用于人类膀胱肿瘤样本。肿瘤将被分组 分阶段以确定每组的相关基因组。这些 然后，基因组将用于测试不同组中的预后效用 患者样本。具体目标是： 目标 1. 期间的基因改变 膀胱癌进展。我们将检验肿瘤通路的假设 进展是由基因决定的。 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 浅表疾病级别（100pT1 肿瘤和 50 pTis）。 C. 肌肉侵入 疾病 (150) 肿瘤将用于识别基因改变的模式 并且表情会根据阶段而变化。 D. 浅表间质变化 和侵袭性癌症：合作者制备的肿瘤成纤维细胞（Hayward 博士） 将用于定义肿瘤基质中改变的基因表达模式 （与远离肿瘤的成纤维细胞相比）。鉴定出的候选基因 然后将测试这些研究与肿瘤分期的关联。目标2。 基因改变作为临床结果的预测因子。候选基因 将测试目标 1 中确定的改变与临床的关联 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，以确定与 囊泡内卡介苗和吉西他滨治疗后的结果。 A、高风险 肌肉浸润性肿瘤。将在淋巴结患者中测试分子标记 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 治疗反应的标志物，以及作为对 MVAC 治疗反应的标志物 紫杉烷类。 C. 使用组织阵列验证候选标记。我们将使用 组织阵列来验证目标 1 中识别的标记并在 目标 2A-B。