title: Clinical significance of previously cryptic copy number alterations and loss of heterozygosity in pediatric acute myeloid leukemia and myelodysplastic syndrome determined using combined array comparative genomic hybridization plus single-nucleotide polymorphism microarray analyses.
abstract: The combined array comparative genomic hybridization plus single-nucleotide polymorphism microarray (CGH+SNP microarray) platform can simultaneously detect copy number alterations (CNA) and copy-neutral loss of heterozygosity (LOH). Eighteen children with acute myeloid leukemia (AML) (n=15) or myelodysplastic syndrome (MDS) (n=3) were studied using CGH+SNP microarray to evaluate the clinical significance of submicroscopic chromosomal aberrations. CGH+SNP microarray revealed CNAs at 14 regions in 9 patients, while metaphase cytogenetic (MC) analysis detected CNAs in 11 regions in 8 patients. Using CGH+SNP microarray, LOHs>10 Mb involving terminal regions or the whole chromosome were detected in 3 of 18 patients (17%). CGH+SNP microarray revealed cryptic LOHs with or without CNAs in 3 of 5 patients with normal karyotypes. CGH+SNP microarray detected additional cryptic CNAs (n=2) and LOHs (n=5) in 6 of 13 patients with abnormal MC. In total, 9 patients demonstrated additional aberrations, including CNAs (n=3) and/or LOHs (n=8). Three of 15 patients with AML and terminal LOH>10 Mb demonstrated a significantly inferior relapse-free survival rate (P=0.041). This study demonstrates that CGH+SNP microarray can simultaneously detect previously cryptic CNAs and LOH, which may demonstrate prognostic implications.
authors.affiliation: Division of Pediatric Hematology/Oncology, Asan Medical Center Children's Hospital, Department of Pediatrics, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Kyung-Nam
authors.identifier: 0000-0002-6376-672X
authors.initials: KN
authors.lastname: Koh
authors.affiliation: Genome Research Center, Asan Medical Center, Seoul, Korea.
authors.forename: Jin Ok
authors.identifier: 0000-0002-0917-5312
authors.initials: JO
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Eul Ju
authors.identifier: 0000-0002-8247-3746
authors.initials: EJ
authors.lastname: Seo
authors.affiliation: Division of Pediatric Hematology/Oncology, Asan Medical Center Children's Hospital, Department of Pediatrics, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Seong Wook
authors.identifier: 0000-0001-7471-2287
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Division of Pediatric Hematology/Oncology, Asan Medical Center Children's Hospital, Department of Pediatrics, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jin Kyung
authors.identifier: 0000-0002-4572-514X
authors.initials: JK
authors.lastname: Suh
authors.affiliation: Division of Pediatric Hematology/Oncology, Asan Medical Center Children's Hospital, Department of Pediatrics, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Ho Joon
authors.identifier: 0000-0001-8799-4068
authors.initials: HJ
authors.lastname: Im
authors.affiliation: Division of Pediatric Hematology/Oncology, Asan Medical Center Children's Hospital, Department of Pediatrics, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jong Jin
authors.identifier: 0000-0002-0191-7836
authors.initials: JJ
authors.lastname: Seo
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D004247:DNA / Q000032:analysis* / Q000378:metabolism; D056915:DNA Copy Number Variations; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D019656:Loss of Heterozygosity; D008297:Male; D009190:Myelodysplastic Syndromes / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D014184:Transplantation, Homologous
chemical_list: D004247:DNA
keywords: Comparative Genomic Hybridization; DNA Copy Number Variations; Leukemia, Myeloid, Acute; Loss of Heterozygosity; Single-Nucleotide Polymorphism Microarray