Trial Information

Identifying Rare Genetic Variants Involved in High Risk Acute Lymphoblastic Leukemia (ALL) Via Pooled DNA Sequencing

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.