Trial Information

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

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.