MolecularAnalysis of Ethnic Variations in Wilms' Tumor

肾母细胞瘤种族变异的分子分析

• 批准号: 8335428
• 负责人: Harold Newton Lovvorn
• 金额: $ 17.18万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-20 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8335428
• 关键词: Africa; African; African American; Algorithms; American; Archives; Behavior; Bioinformatics; Biological; Biology; Buffers; Cancer Center; Caring; Caucasians; Caucasoid Race; Child; Childhood; Children' s Oncology Group; Clinical Data; Collaborations; Collection; Commit; Country; Data; Developing Countries; Development; Disease; Enrollment; Epidemiologic Studies; Equipment; Ethnic Origin; Ethnic group; Formalin; Foundations; Future; Genetic; Genetic Drift; Genetic Heterogeneity; Genetic Predisposition to Disease; Hospitals; Image; Incidence; Institutes; International; Kenya; Kidney; Letters; Liquid substance; MALDI-TOF Mass Spectrometry; Malignant Neoplasms; Mass Spectrum Analysis; Metabolism; Mission; Molecular; Molecular Profiling; Nationalities; Nephroblastoma; Nitrogen; Operative Surgical Procedures; Outcome; Paraffin Embedding; Pathologist; Pathway interactions; Patients; Peptides; Pharmacotherapy; Plant Roots; Population; Populations at Risk; Proteins; Proteome; Proteomics; Publishing; Race; Recurrent disease; Registries; Renal carcinoma; Reporting; Research; Resources; Risk; Risk Factors; Sampling; Secure; Shapes; Specimen; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Time; Tissues; Training; Treatment Protocols; Tumor Biology; Tumor Tissue; Underserved Population; Universities; Urine; Variant; adverse outcome; base; career; caucasian American; design; empowered; experience; global health; high risk; improved; innovation; insight; multidisciplinary; neoplasm registry; new therapeutic target; novel; patient registry; protein expression; repository; sample fixation; tool; tumor; tumor registry; urinary

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. .

描述（由申请人提供）：这项为期两年的研究旨在探索威尔姆斯肿瘤致死儿童肾脏癌致死儿童肾癌发育和进展的族裔差异的生物学基础。几项流行病学研究表明，与所有其他种族的公民身份相比，黑人血统的孩子具有最高的风险来发展Wilms的肿瘤，这表明在这种疾病的发展方面具有特定民族的生物学。尽管治疗方案的入学人数相似，但北美黑人血统的北美儿童的存活率也较低，这进一步暗示了肿瘤生物学不同或对治疗算法的反应性，而不是获得适当治疗的差异。但是，尚未据报道，在种族多样的Wilms肿瘤患者中，尚无研究分子或遗传病因的分子或遗传病因。鉴于不同的族裔群体具有独特的遗传背景，并且具有药物治疗代谢不同途径的潜力，因此这些研究的长期目标是确定族裔特异性Wilms肿瘤疗法发展的新颖目标。这些研究的短期目的是首先将分子签名分配给Wilms的肿瘤组织，该肿瘤组织预示了种族之间不良结果。对种族之间独特的生物学的这种理解将为减少威尔姆斯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，以探索Wilms肿瘤在高加索裔美国人，非裔美国人和唯一风险和遗传多样化的黑人肯尼亚儿童之间的分子基础。三个具体的研究目标是交织的，将涉及多学科的多机构合作，并确保了范德比尔特全球健康研究所（VIGH）的专业知识和支持。利用范德比尔特质谱研究中心的Vigh和专业知识的巨大资源，我们最初将探索肯尼亚在肯尼亚独特风险和服务不足的Wilms肿瘤患者中的蛋白质组学差异。将将肯尼亚·威尔姆斯肿瘤患者产生的结果与通过范德比尔特和儿童肿瘤学组储备金获得的非裔美国人和高加索裔美国儿童收集的标本进行比较。将使用质谱法（MALDI-TOF）分析原发性Wilms的肿瘤组织和疗法前尿液，以建立特定于种族的蛋白质表达的分子指纹。 。