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 Polymo.
10.3346/jkms.2014.29.7.926
- Author:
Kyung Nam KOH
1
;
Jin Ok LEE
;
Eul Ju SEO
;
Seong Wook LEE
;
Jin Kyung SUH
;
Ho Joon IM
;
Jong Jin SEO
Author Information
1. Division of Pediatric Hematology/Oncology, Asan Medical Center Children's Hospital, Department of Pediatrics, University of Ulsan College of Medicine, Seoul, Korea. jjseo@amc.seoul.kr
- Publication Type:Original Article ; Comparative Study ; Research Support, Non-U.S. Gov't
- Keywords:
Leukemia, Myeloid, Acute;
DNA Copy Number Variations;
Loss of Heterozygosity;
Comparative Genomic Hybridization;
Single-Nucleotide Polymorphism Microarray
- MeSH:
Adolescent;
Child;
Child, Preschool;
Chromosome Aberrations;
*Comparative Genomic Hybridization;
DNA/*analysis/metabolism;
DNA Copy Number Variations;
Female;
Hematopoietic Stem Cell Transplantation;
Humans;
Infant;
Kaplan-Meier Estimate;
Leukemia, Myeloid, Acute/*diagnosis/*genetics/therapy;
Loss of Heterozygosity;
Male;
Myelodysplastic Syndromes/*diagnosis/*genetics/therapy;
*Oligonucleotide Array Sequence Analysis;
Polymorphism, Single Nucleotide;
Real-Time Polymerase Chain Reaction;
Transplantation, Homologous
- From:Journal of Korean Medical Science
2014;29(7):926-933
- CountryRepublic of Korea
- Language:English
-
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.
