Genes disrupted be a t(5;6) in a Wilms Tumor Patients

肾母细胞瘤患者的 t(5;6) 基因被破坏

• 批准号: 6678479
• 负责人: MICHAEL Joseph HIGGINS
• 金额: $ 18.52万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6678479
• 关键词: Wilms' tumor; chromosome translocation; clinical research; disease /disorder etiology; fluorescent in situ hybridization; functional /structural genomics; gene expression; gene mutation; genetic library; genetic mapping; genetic regulatory element; high performance liquid chromatography; human tissue; hybrid cells; mathematics; methylation; molecular cloning; neoplasm /cancer genetics; nucleic acid sequence; polymerase chain reaction

DESCRIPTION (provided by applicant): Wilms' tumor of the kidney is one of the most common pediatric cancers and is a leading cause of cancer mortality in children worldwide. Wilms' tumor occurs in both familial and sporadic forms and is believed to arise from persistent metanephric blastema resulting from a failure of differentiation. The WT1 gene was identified more than 10 years ago and, despite the efforts of several laboratories, remains the only tumor suppressor gene known to be involved in Wilms' tumor. However, WT1 is involved in less than 10% of cases suggesting that other genes must be involved. The analysis of chromosome rearrangement breakpoints, particularly translocations, has been extremely successful in the discovery of novel genes involved in cancer. The goals of the studies proposed in this application are to identify the gene or genes affected by an apparently balanced constitutional t(5;6)(q21;q21) identified in a patient with bilateral Wilms' tumor and to test these genes for involvement in our panel of Wilms' tumors. The 6q21 region is involved in three other reported cases of translocations associated with Wilms' tumor and most likely harbors the relevant gene(s). The two derivative chromosomes resulting from this rearrangement have been segregated into somatic cell hybrids which provide powerful reagents to precisely localize the breakpoint regions on chromosome 5 and 6. The specific aims of this proposal are: 1. Precisely locate rearrangement breakpoints of the t(5;6)(q21;q21) in a patient with bilateral Wilms' tumor. 2. Identify the gene(s) disrupted by the Wilms' tumor associated t(5;6)(q21;q21). 3. Analyze our collection of Wilms' tumors for mutations, rearrangements, promoter methylation and altered expression of genes identified in Specific Aim 2. The identification of novel genes that contribute to the etiology of Wilms' tumor will help elucidate the mechanisms by which differentiating kidney cells become transformed during development. Furthermore, the characterization of these genes may provide novel opportunities for diagnosis and treatment of this cancer.

描述（由申请人提供）：Wilms的肾脏肿瘤是最常见的儿科癌症之一，是全球儿童癌症死亡率的主要原因。威尔姆斯的肿瘤以家族性和零星形式出现，被认为是由于分化失败而引起的持续性跨虫胚芽引起的。十多年前发现了WT1基因，尽管有几个实验室的努力，但仍然是唯一已知参与Wilms肿瘤的肿瘤抑制基因。但是，WT1涉及不到10％的病例，表明必须涉及其他基因。在发现涉及癌症的新基因时，染色体重排断点，尤其是易位的分析非常成功。本应用中提出的研究的目标是确定受到双侧Wilms肿瘤患者鉴定出的明显平衡的宪法t（5; 6）（Q21; Q21）影响的基因或基因，并测试了这些基因在我们的Wilms肿瘤小组中参与其中。 6q21区域参与了其他三个与Wilms肿瘤有关的易位病例，很可能是相关基因。该重排产生的两个衍生染色体已被隔离到体细胞杂种中，这些染色体提供了强大的试剂，以精确地将断点区域定位在5和6染色体上。 该提案的具体目的是： 1。精确定位双侧Wilms肿瘤患者的T（5; 6）（Q21; Q21）的重排断点。 2。识别受Wilms肿瘤相关t（5; 6）（q21; q21）破坏的基因。 3.分析我们的Wilms肿瘤收集的突变，重排，启动子甲基化和在特定目标中鉴定的基因表达的改变。鉴定新的基因的鉴定，这些基因有助于Wilms肿瘤的病因，这将有助于阐明在发育过程中区分肾细胞在发育过程中转化的机制。此外，这些基因的特征可能为诊断和治疗该癌症提供新的机会。