CATEGORIZATION OF WILMS TUMOR BY GENETIC EXPRESSION

根据基因表达对肾母细胞瘤进行分类

• 批准号: 6693352
• 负责人: Elizabeth J Perlman
• 金额: $ 30.96万
• 依托单位: LURIE CHILDREN'S HOSPITAL OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-18 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6693352
• 关键词: Wilms' tumor; clinical research; complementary DNA; cooperative study; gene expression; genetic markers; human subject; immunocytochemistry; in situ hybridization; metastasis; microarray technology; neoplasm /cancer classification /staging; neoplasm /cancer genetics; neoplasm /cancer pharmacology; pediatric neoplasm /cancer

DESCRIPTION: (Applicant's Description) Wilms tumor represents the most common renal neoplasm of childhood. Remarkable success has been achieved in the therapy of WT through the National Wilms Tumor Study Group (NWTS). Despite the responsiveness of most WT to adjuvant chemotherapy, some tumors are unresponsive and result in tumor progression and death. Most tumors lack distinctive histologic or clinical features to enable targeting with more or less aggressive chemotherapy. Recognizing biologically distinctive subsets of WT may be useful for predicting clinical behavior and targeting therapy. The goal of this project is to identify molecular categories of WT that have predictable clinical properties, including propensity to metastasize and response to therapy. We hypothesize that gene expression profiles will aid in the recognition of these categories. AIM ONE: To identify candidate marker genes that are differentially expressed: Using commercially available cDNA macro-arrays, we will comprehensively analyze gene expression in a small group of Wilms tumors. A subset of genes whose expression varies throughout these tumors will be identified. AIM TWO: To identify molecular categories of Wilms tumor based upon the expression of candidate marker genes identified in Aim One: Utilizing custom cDNA microarrays approximately 200-300 pathologically, clinically and genetically characterized WT will be analyzed. Using computationally assisted methods, profiles of gene expression that define molecular categories of Wilms tumors will be identified. AIM THREE: To verify, test, and model the new molecular categories of Wilms tumor and to examine these new categories in their clinical, pathologic, and genetic context. Each molecular category will be analyzed and validated for clinical, pathologic and genetic features using the extensive resources of the NWTS. Genes predictive of molecular categories will be verified using in situ hybridization or immunohistochemistry. A model categorization will be proposed and tested on 200 additional Wilms tumors.

描述：（申请人的描述）Wilms肿瘤代表最常见的 儿童期肾脏肿瘤。 在 通过国家威尔姆斯肿瘤研究小组（NWTS）对WT进行治疗。 尽管 大多数WT对辅助化疗的反应能力，某些肿瘤是 无反应，导致肿瘤的进展和死亡。 大多数肿瘤缺乏 独特的组织学或临床特征，以更多或更多 侵略性较低的化学疗法。 识别生物学独特的子集 WT可能有助于预测临床行为和靶向治疗。 这 该项目的目标是确定具有的分子类别 可预测的临床特性，包括转移和 对治疗的反应。 我们假设基因表达谱将有助于 这些类别的认可。 目标一：识别差异性的候选标记基因 表达：使用市售的cDNA宏观阵列，我们将 全面分析了一小组Wilms肿瘤中的基因表达。 一个 在这些肿瘤中的表达变化的基因子集将是 确定。 目标二：基于 AIM ONE中鉴定出的候选标记基因的表达：利用自定义 cDNA微阵列在病理，临床和 将分析具有遗传特征的WT。 使用计算辅助 方法，定义Wilms分子类别的基因表达的曲线 肿瘤将被鉴定。 目标三：验证，测试和建模Wilms的新分子类别 肿瘤并检查这些新类别的临床，病理学和 遗传环境。 每个分子类别将进行分析和验证 使用大量资源的临床，病理和遗传特征 NWTS。 将使用原位验证分子类别的基因 杂交或免疫组织化学。 模型分类将是 提议并对其他200个Wilms肿瘤进行了测试。