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
- 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
- Assess the global expression of microRNAs in leukemic lymphoblasts using microRNA gene
- 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
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.
Identification of regions of copy number abnormalities (CNA) and uniparental disomy in leukemic lymphoblasts using Affymetrix GeneChip Mapping 500K array sets
Stephen P. Hunger, MD
Children's Hospital Colorado Center for Cancer and Blood Disorders
|Hollings Cancer Center at Medical University of South Carolina||Charleston, South Carolina 29425|