Biomarkers in DNA Samples From Patients With High-Risk Acute Lymphoblastic Leukemia

OBJECTIVES:

• To perform pooled DNA sequencing in 56 genes from the genomic DNA of unaffected children and matched non-tumor and blast DNA from patients with high-risk (HR) acute lymphoblastic leukemia (ALL) enrolled on COG HR ALL protocols.
• To identify loci enriched for genetic variation between DNA of unaffected children and DNA of these patients.
• To individually validate novel, putatively functional single nucleotide polymorphisms (SNPs) identified via pooled sequencing with another genotyping platform.
• To correlate HR ALL with clinical phenotypes, co-morbidities, toxicities, outcomes to the genes or pathways found to harbor a significant increase in genetic variation.

OUTLINE: DNA specimens from unaffected children (pool 1) and from patients with non-tumor (pool 2) and leukemia blasts (pool 3) are analyzed for genetic pathophysiology of pre-B acute lymphoblastic leukemia by microarray and PCR assays. Sequencing is performed on each of the 3 PCR pools of DNA.