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是独特的设计，以探索致命的儿童肾癌，肾母细胞瘤的发展和进展的种族差异的生物学基础。一些流行病学研究表明，与所有其他种族群体相比，无论国籍如何，非洲黑人血统的儿童患维尔姆斯瘤的风险最高，这表明这种疾病的发展具有种族特异性生物学。尽管在治疗方案中的入组相似，但非洲黑人血统的北美儿童的生存率也较低，这进一步意味着不同的肿瘤生物学或对治疗算法的反应性，而不是获得适当治疗的差异。然而，没有分析研究这些不同的发病率在种族不同的肾母细胞瘤患者的分子或遗传病因的报告。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为开发种族特异性威尔姆斯肿瘤疗法确定新的靶点。这些研究的短期目标首先是为Wilms肿瘤组织分配一个分子特征，这预示着种族之间的不良结果。对种族之间独特生物学的这种理解将为减少未来观察到的Wilms肿瘤结果差异奠定基础。这些研究将涉及一种创新的方法来探索白人美国人，黑人非洲裔美国人和独特的风险和遗传多样性较低的肯尼亚黑人儿童之间Wilms肿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，并获得了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独特的高危和服务不足的维尔姆斯肿瘤患者人群的蛋白质组差异。从肯尼亚威尔姆斯肿瘤患者中产生的结果将与从非洲裔美国人和高加索裔美国儿童中收集的标本进行比较，这些标本可通过范德比尔特和儿童肿瘤学小组储存库获得。将使用质谱法（MALDI-TOF）分析原发性肾母细胞瘤组织和治疗前尿液，以建立种族特异性蛋白表达的分子指纹。.