Molecular Profiling and Candidate Gene Analysis in Pediatric Gliomas

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DESCRIPTION (provided by applicant): Pediatric low-grade gliomas constitute the most common group of solid tumors in children. Despite the utilization of a variety of cytogenetic and molecular approaches, the primary genetic events associated with the development of pediatric low-grade gliomas are largely unknown. Although the majority of children may be cured with surgery alone, tumors can recur. Often the recurrences are of a higher malignancy grade, and may be resistant to treatment. There are currently no histologic or biologic markers that can be used to identify which patients are at an increased risk for recurrence. With recent developments in array technology, we now have the opportunity to characterize the genomic alterations in pediatric gliomas at an extremely high level of resolution. We hypothesize that specific non-random chromosomal imbalances will be detected using these approaches. In this application, we propose three specific aims. In aim 1, we will analyze a series of pediatric astrocytomas and gangliogliomas using 550K single polymorphism nucleotide arrays from Ilumina. Chromosomal gains and losses, as well as regions of copy number neutral loss of heterozygosity will be identified. In aim 2, we will validate the array results and identify candidate genes using a combination of fluorescence in situ hybridization, DNA and RNA analysis and immunohistochemistry. In aim 3, specific markers and potential candidate genes will be analyzed in a series of low and high-grade gliomas from both children and adults to determine the specificity of the markers or genomic alterations for different groups of patients. The ultimate goal of this Research is to identify specific markers that can be used as an aid in the diagnosis, prognosis, and ultimate treatment of gliomas in children. PUBLIC HEALTH RELEVANCE: Pediatric gliomas are the most common types of solid tumors in children. We will use high-density single nucleotide polymorphism arrays to detect novel chromosomal changes in these tumors. Our studies will form the basis for ultimate identification of the genes that are responsible for the development or progression of gliomas, thus allowing for development of biologically based treatment strategies.