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 |
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| Authors: | Kyung-Nam Koh Jin Ok Lee Eul Ju Seo Seong Wook Lee Jin Kyung Suh Ho Joon Im Jong Jin Seo |
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| Affiliation: | 1.Division of Pediatric Hematology/Oncology, Asan Medical Center Children''s Hospital, Department of Pediatrics, University of Ulsan College of Medicine, Seoul, Korea.;2.Genome Research Center, Asan Medical Center, Seoul, Korea.;3.Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. |
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| 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.Graphical Abstract | |
| Keywords: | Leukemia, Myeloid, Acute DNA Copy Number Variations Loss of Heterozygosity Comparative Genomic Hybridization Single-Nucleotide Polymorphism Microarray |
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