MolecularAnalysis of Ethnic Variations in Wilms' Tumor

描述（由申请人提供）：这项为期两年的研究旨在探索致命性儿童肾癌Wilms肿瘤发生和发展过程中种族差异的生物学基础。几项流行病学研究表明，与所有其他种族相比，非洲黑人血统的儿童患威尔姆斯瘤的风险最高，而与国籍无关，这表明这种疾病的发展具有种族特异性生物学。尽管采用了类似的治疗方案，但北美非洲黑人血统的儿童的存活率也较低，这进一步暗示了不同的肿瘤生物学或对治疗算法的反应性，而不仅仅是获得适当治疗的差异。然而，在不同种族的Wilms肿瘤患者中，没有分析这些不同发病率的分子或遗传病因的报道。鉴于不同种族群体具有独特的遗传背景和不同药物治疗代谢途径的潜力，这些研究的长期目标是确定开发种族特异性Wilms肿瘤治疗的新靶点。这些研究的短期目标首先是为Wilms肿瘤组织分配一种分子特征，这种分子特征预示着不同种族之间的不良后果。这种对种族间独特生物学的理解将为将来减少Wilms肿瘤的观察结果差异奠定基础。这些研究将涉及一种创新的方法，探索高加索美国人、非洲裔美国黑人和独特的风险和基因多样性较低的肯尼亚黑人儿童之间威尔姆斯瘤不同行为的分子基础。这三个具体的研究目标是相互交织的，将涉及多学科、多机构的合作，并已获得范德比尔特全球卫生研究所（VIGH）的专业知识和支持。利用VIGH的巨大资源和范德比尔特质谱研究中心的专业知识，我们将首先探索肯尼亚Wilms肿瘤患者独特的风险和服务不足人群的蛋白质组学差异。来自肯尼亚威尔姆斯肿瘤患者的结果将与从范德比尔特大学和儿童肿瘤小组知识库中收集的非裔美国人和高加索美国儿童的标本进行比较。原发Wilms肿瘤组织和治疗前尿液将使用质谱法（MALDI-TOF）进行分析，以建立种族特异性蛋白表达的分子指纹图谱。

DESCRIPTION (provided by applicant): This two-year study is uniquely designed to explore the biological basis for ethnic variations in the development and progression of the lethal childhood kidney cancer, Wilms' tumor. Several epidemiological studies have shown that children of black African ancestry carry the highest risk to develop Wilms' tumor when compared with all other ethnic groups regardless of country citizenship, which suggests an ethnic-specific biology in the development of this disease. North American children of black African ancestry have also been shown to have a lower survival despite similar enrollment in treatment protocols, which further implies a different tumor biology or responsiveness to therapy algorithms more than a disparity in access to adequate therapy. However, no analyses examining the molecular or genetic etiology for these different incidence rates among ethnically diverse Wilms' tumor patients have been reported. Given that diverse ethnic groups have unique genetic backgrounds and the potential for different pathways of drug therapy metabolism, the long-term objective of these studies is to identify novel targets for the development of ethnic-specific Wilms' tumor therapies. The short-term aim of these studies is first to assign a molecular signature to Wilms' tumor tissues that portend adverse outcomes between ethnic groups. Such an understanding of the unique biology between ethnic groups will lay the groundwork to reduce observed outcome disparities for Wilms' tumor in the future. These studies will involve an innovative approach to exploring the molecular basis for the disparate behavior of Wilms' tumor between Caucasian-American, black African-American and uniquely at-risk and less genetically diverse black Kenyan children. The three specific study aims are interwoven and will involve a multidisciplinary, multi-institutional collaboration, having secured the expertise and support of the Vanderbilt Institute for Global Health (VIGH). Taking advantage of the tremendous resources at the VIGH and expertise within the Mass Spectrometry Research Center at Vanderbilt, we will initially explore proteomic differences in the uniquely at- risk and underserved population of Wilms' tumor patients in Kenya. Results generated from Kenyan Wilms' tumor patients will be compared with specimens collected from African-American and Caucasian-American children, available through Vanderbilt and the Children's Oncology Group repositories. Primary Wilms' tumor tissue and pre-therapy urine will be analyzed using mass spectrometry (MALDI-TOF) to establish a molecular fingerprint of protein expression specific to ethnicity. .