MolecularAnalysis of Ethnic Variations in Wilms' Tumor

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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. . PUBLIC HEALTH RELEVANCE: This two-year study will lay the foundation for exploring ethnic disparities in the development and behavior of the lethal childhood kidney cancer, Wilms' tumor. Through these studies, a molecular fingerprint of Wilms' tumor specific to black African ancestry will be characterized that will one day shape treatment regimens according to ethnicity. These studies further will empower the developing nation of Kenya with the tools necessary to study and improve therapies according to biology specific to its children.