Integration of cytogenomic data for furthering the characterization of pediatric B-cell acute lymphoblastic leukemia: a multi-institution, multi-platform microarray study

Linda B Baughn; Jaclyn A Biegel; Sarah T South; Teresa A Smolarek; Suzanne Volkert; Andrew J Carroll; Nyla A Heerema; Karen R Rabin; Patrick A Zweidler-McKay; Mignon Loh; Betsy Hirsch

doi:10.1016/j.cancergen.2014.11.003

Integration of cytogenomic data for furthering the characterization of pediatric B-cell acute lymphoblastic leukemia: a multi-institution, multi-platform microarray study

Cancer Genet. 2015 Jan-Feb;208(1-2):1-18. doi: 10.1016/j.cancergen.2014.11.003. Epub 2014 Nov 21.

Authors

Affiliations

¹ Department of Laboratory Medicine and Pathology and Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
² Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
³ ARUP Laboratories, Department of Pathology, University of Utah, Salt Lake City, UT, USA.
⁴ Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
⁵ Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
⁶ Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
⁷ Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA.
⁸ Department of Pediatrics, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
⁹ Department of Pediatrics, Benioff Children's Hospital and the Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
¹⁰ Department of Laboratory Medicine and Pathology and Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA. Electronic address: hirsc003@umn.edu.

Abstract

It is well documented that among subgroups of B-cell acute lymphoblastic leukemia (B-ALL), the genetic profile of the leukemic blasts has significant impact on prognosis and stratification for therapy. Recent studies have documented the power of microarrays to screen genome-wide for copy number aberrations (CNAs) and regions of copy number-neutral loss of heterozygosity (CNLOH) that are not detectable by G-banding or fluorescence in situ hybridization (FISH). These studies have involved application of a single array platform for the respective cases. The present investigation demonstrates the feasibility and usefulness of integrating array results from multiple laboratories (ARUP, The Children's Hospital of Philadelphia, Cincinnati Children's Hospital Medical Center, and University of Minnesota Medical Center) that utilize different array platforms (Affymetrix, Agilent, or Illumina) in their respective clinical settings. A total of 65 patients enrolled on the Children's Oncology Group (COG) study AALL08B1 were identified for study, as cytogenetic and FISH studies had also been performed on these patients, with a central review of those results available for comparison. Microarray data were first analyzed by the individual laboratories with their respective software systems; raw data files were then centrally validated using NEXUS software. The results demonstrated the added value of integrating multi-platform data with cytogenetic and FISH data and highlight novel findings identified by array including the co-occurrence of low and high risk abnormalities not previously reported to coexist within a clone, novel regions of chromosomal amplification, clones characterized by numerous whole chromosome LOH that do not meet criteria for doubling of a near-haploid, and characterization of array profiles associated with an IKZF1 deletion. Each of these findings raises questions that are clinically relevant to risk stratification.

Keywords: B-ALL; ETV6-RUNX1; IKZF1; hypodiploid; iAMP21; microarray.

Publication types

Multicenter Study
Research Support, N.I.H., Extramural

MeSH terms

B-Lymphocytes / metabolism*
B-Lymphocytes / pathology
Child
Chromosome Aberrations
Chromosome Banding
Comparative Genomic Hybridization / methods*
Cytogenetic Analysis / methods*
DNA Copy Number Variations
Female
Humans
In Situ Hybridization, Fluorescence
Karyotyping
Loss of Heterozygosity
Male
Oligonucleotide Array Sequence Analysis
Polymorphism, Single Nucleotide
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
Prognosis
Reproducibility of Results
Sensitivity and Specificity

Abstract

Publication types

MeSH terms

Grants and funding