CATEGORIZATION OF WILMS TUMOR BY GENETIC EXPRESSION

描述：(申请人的描述)肾母细胞瘤是最常见的肿瘤 儿童时期的肾脏肿瘤。在这方面取得了显著成就 通过国家Wilms肿瘤研究小组(NWTS)进行WT的治疗。尽管 大多数WT对辅助化疗的反应性，一些肿瘤是 无反应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，使靶向更多或 不那么激进的化疗。识别生物上不同的子集 WT可用于预测临床行为和靶向治疗。这个 该项目的目标是确定WT的分子类别 可预测的临床特征，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 对这些类别的认识。 目标一：寻找差异表达的候选标记基因 表达：使用商用的cDNA宏阵列，我们将 综合分析一小群肾母细胞瘤的基因表达。一个 在这些肿瘤中表达变化的基因子集将是 已确认身份。 目的二：根据肾母细胞瘤的分子分类鉴定肾母细胞瘤 目标一中确定的候选标记基因的表达：利用习惯 CDNA微阵列约200-300个病理，临床和 将分析具有遗传特征的WT。使用计算辅助 方法，确定Wilms分子类别的基因表达谱 肿瘤将被识别出来。 目标三：验证、测试和模拟Wilms的新分子类别 并检查这些新的类别在他们的临床、病理和 遗传背景。将对每个分子类别进行分析和验证 临床、病理和遗传特征利用丰富的资源 NWTS。预测分子类别的基因将通过原位验证 杂交或免疫组织化学。模型分类将是 建议在另外200个Wilms肿瘤上进行测试。

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.