Childhood Cancer Therapeutically Applicable Research to Generate Effective Treatments (TARGET) Initiative High-Risk ALL Pilot Project: Application of Array-Based Methods and Gene Re-Sequencing to Identify Candidate Molecular Targets for High-Risk Pediatric Acute Lymphoblastic Leukemia

Brief Summary

Detailed Description

OBJECTIVES: * Identify regions of copy number abnormalities (CNA) and uniparental disomy in leukemic lymphoblasts from pediatric patients with high-risk acute lymphoblastic leukemia (ALL) using Affymetrix GeneChip Mapping 500K array sets. (Pilot project) * Identify regions of CNA and loss-of-heterozygosity using Affymetrix SNP 6.0 microarrays. (Expansion project) * Define gene expression profiles for leukemic lymphoblasts using Affymetrix U133 Plus 2.0 arrays. * Assess the global expression of microRNAs in leukemic lymphoblasts using microRNA gene chips. * Utilize array-generated gene expression data and data for CNAs and uniparental disomy to prioritize candidate genes and genomic regions for resequencing. * Characterize epigenomic profiles using the HpaII tiny fragment Enrichment by Ligation-mediated PCR (HELP) assay. (Expansion project) * Discover candidate therapeutic targets for these patients by identifying genes that are consistently mutated in leukemic lymphoblasts using high-throughput focused gene resequencing. (Pilot project) * Discover candidate therapeutic targets for these patients by next generation sequencing technologies, including whole genome, whole transcriptome, and whole exome. (Expansion project) OUTLINE: This is a multicenter study. Banked biological samples (bone marrow and peripheral blood) are analyzed using gene expression profiling, single-nucleotide polymorphism and genotyping assays, DNA copy number and loss of heterozygosity estimates, epigenetic profiling, and gene resequencing. PROJECTED ACCRUAL: A total of 150 patient samples will be accrued for this study.

Primary Outcomes