title: Implementation of high resolution single nucleotide polymorphism array analysis as a clinical test for patients with hematologic malignancies.
abstract: Single nucleotide polymorphism-based oligonucleotide arrays have been used as a research tool to detect genomic copy number changes and allelic imbalance in a variety of hematologic malignancies and solid tumors. The high resolution, genome-wide coverage, minimal DNA requirements, and relatively short turnaround time are advantageous for use in a clinical setting. We validated the Illumina HumanHap550 BeadChip array for clinical use by analyzing 127 pediatric leukemia and lymphoma samples that had previously been characterized by means of standard cytogenetic analysis and fluorescence in situ hybridization. A higher resolution Illumina HumanHap610 BeadChip array was ultimately used for clinical testing. To date, 180 samples from children with a suspected or confirmed hematologic malignancy have been analyzed. Of the 180 clinical samples, 130 (72%) bone marrow or lymphoma specimens had aberrations revealed by the array that were not seen in the karyotypes. These typically included deletions in genes associated with B- or T-cell malignancies, such as CDKN2A/B, PAX5, and IKZF1. There were also 75 regions of copy number neutral loss of heterozygosity (>5 Mb threshold) detected in 49 samples in this cohort, which could be categorized as constitutional or acquired abnormalities. On the basis of our experience in the last 2 years, we suggest that single nucleotide polymorphism arrays are a valuable addition to, but not a replacement for, standard cytogenetic approaches for hematologic malignancies.
authors.affiliation: Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Dougherty
authors.forename: Donna M
authors.initials: DM
authors.lastname: Wilmoth
authors.forename: Laura S
authors.initials: LS
authors.lastname: Tooke
authors.forename: Tamim H
authors.initials: TH
authors.lastname: Shaikh
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Gai
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.forename: Jaclyn A
authors.initials: JA
authors.lastname: Biegel
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D017353:Gene Deletion; D018628:Gene Dosage; D055106:Genome-Wide Association Study; D019337:Hematologic Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D007621:Karyotyping; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014178:Translocation, Genetic
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; C084103:BCL6 protein, human; C493966:CDKN2B protein, human; C067143:TAL1 protein, human