title: Screening for copy-number alterations and loss of heterozygosity in chronic lymphocytic leukemia--a comparative study of four differently designed, high resolution microarray platforms.
abstract: Screening for gene copy-number alterations (CNAs) has improved by applying genome-wide microarrays, where SNP arrays also allow analysis of loss of heterozygozity (LOH). We here analyzed 10 chronic lymphocytic leukemia (CLL) samples using four different high-resolution platforms: BAC arrays (32K), oligonucleotide arrays (185K, Agilent), and two SNP arrays (250K, Affymetrix and 317K, Illumina). Cross-platform comparison revealed 29 concordantly detected CNAs, including known recurrent alterations, which confirmed that all platforms are powerful tools when screening for large aberrations. However, detection of 32 additional regions present in 2-3 platforms illustrated a discrepancy in detection of small CNAs, which often involved reported copy-number variations. LOH analysis using dChip revealed concordance of mainly large regions, but showed numerous, small nonoverlapping regions and LOH escaping detection. Evaluation of baseline variation and copy-number ratio response showed the best performance for the Agilent platform and confirmed the robustness of BAC arrays. Accordingly, these platforms demonstrated a higher degree of platform-specific CNAs. The SNP arrays displayed higher technical variation, although this was compensated by high density of elements. Affymetrix detected a higher degree of CNAs compared to Illumina, while the latter showed a lower noise level and higher detection rate in the LOH analysis. Large-scale studies of genomic aberrations are now feasible, but new tools for LOH analysis are requested.
authors.affiliation: Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Hematology and Transplantation, Lund University, Lund, Sweden.
authors.forename: Rebeqa
authors.initials: R
authors.lastname: Gunnarsson
authors.forename: Johan
authors.initials: J
authors.lastname: Staaf
authors.forename: Mattias
authors.initials: M
authors.lastname: Jansson
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Ottesen
authors.forename: Hanna
authors.initials: H
authors.lastname: Göransson
authors.forename: Ulrika
authors.initials: U
authors.lastname: Liljedahl
authors.forename: Ulrik
authors.initials: U
authors.lastname: Ralfkiaer
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Mansouri
authors.forename: Anne Mette
authors.initials: AM
authors.lastname: Buhl
authors.forename: Karin Ekström
authors.initials: KE
authors.lastname: Smedby
authors.forename: Henrik
authors.initials: H
authors.lastname: Hjalgrim
authors.forename: Ann-Christine
authors.initials: AC
authors.lastname: Syvänen
authors.forename: Ake
authors.initials: A
authors.lastname: Borg
authors.forename: Anders
authors.initials: A
authors.lastname: Isaksson
authors.forename: Jesper
authors.initials: J
authors.lastname: Jurlander
authors.forename: Gunnar
authors.initials: G
authors.lastname: Juliusson
authors.forename: Richard
authors.initials: R
authors.lastname: Rosenquist
mesh_terms: D022202:Chromosomes, Artificial, Bacterial; D018628:Gene Dosage; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D019656:Loss of Heterozygosity; D046208:Microchip Analytical Procedures / Q000379:methods* / Q000592:standards*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide