23 - Utility of Genome-Wide Characterization of B-Cell Acute Lymphoblastic Leukemia Using SNP-Based Microarray

Abstract

Pediatric B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood malignancy, and although event free survival has approached 90%, variability in disease outcomes still persists. At time of diagnosis, cytogenetic analysis of the leukemic clone currently dictates disease risk stratification, optimal therapeutic selection and overall prognosis. Cytogenetic analysis via conventional G-banded chromosome studies and fluorescence in situ hybridization (FISH) for the detection of recurrent rearrangements and characteristic gains and losses is the current gold standard. With the implementation of single nucleotide polymorphism (SNP)-based microarray tools within clinical laboratories (CytoScanHD and OncoScan/Affymetrix), a more precise characterization of B-ALL clones can be achieved. Here we demonstrate the utility of a SNP microarray in 4 illustrative pediatric patient cases seen at the Mayo Clinic Cytogenetics Laboratory to appropriately classify a variety of clinically significant B-ALL clones, including distinguishing hyperdiploidy versus pseudo-hyperdiploidy resulting from a doubled hypodiploid clone, identifying partial homozygous microdeletions of clinically-significant genes (e.g. CDNK2A/B and IKZF1) that fall below the resolution of FISH, and clarifying intrachromosomal amplification of chromosome 21 (iAMP21) unresolved by chromosome and FISH evaluation. These data indicate that the integration of a SNP-based microarray, along with concurrent chromosome and FISH evaluations, offers the most comprehensive cytogenetic analysis of a B-ALL clone.