CATEGORIZATION OF WILMS TUMOR BY GENETIC EXPRESSION

根据基因表达对肾母细胞瘤进行分类

基本信息

批准号：
6514739
负责人：
Elizabeth J Perlman
金额：
$ 25.81万
依托单位：
LURIE CHILDREN'S HOSPITAL OF CHICAGO
依托单位国家：
美国
项目类别：
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/6514739
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

项目摘要

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）肾母细胞瘤是最常见的儿童肾肿瘤。已取得了令人瞩目的成功通过国家肾母细胞瘤研究组 (NWTS) 进行 WT 治疗。尽管大多数 WT 对辅助化疗的反应性，一些肿瘤是反应迟钝并导致肿瘤进展和死亡。大多数肿瘤缺乏独特的组织学或临床特征，以实现更多或更多的靶向不太积极的化疗。识别生物学上独特的子集 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 WT 的分子类别可预测的临床特性，包括转移倾向和对治疗的反应。我们假设基因表达谱将有助于对这些类别的认可。目标一：鉴定差异性的候选标记基因表示：使用市售的 cDNA 宏阵列，我们将全面分析一小群肾母细胞瘤中的基因表达。一个在这些肿瘤中表达不同的基因子集将是确定。目标二：根据以下特征确定肾母细胞瘤的分子类别：目标一中确定的候选标记基因的表达：利用定制 cDNA 微阵列大约 200-300 个病理学、临床和将分析遗传特征的WT。使用计算辅助定义 Wilms 分子类别的方法、基因表达谱肿瘤将被识别。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、病理和遗传背景。每个分子类别都将被分析和验证利用广泛的资源的临床、病理和遗传特征 NWTS。预测分子类别的基因将使用原位验证杂交或免疫组织化学。模型分类将是提出并在另外 200 个肾母细胞瘤上进行了测试。