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Screening for copy-number alterations and loss of heterozygosity in chronic lymphocytic leukemia--a comparative study of four differently designed, high resolution microarray platforms

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  • Rebeqa Gunnarsson
  • Johan Staaf
  • Mattias Jansson
  • Anne Marie Ottesen
  • Hanna Göransson
  • Ulrika Liljedahl
  • Ulrik Ralfkiaer
  • Mahmoud Mansouri
  • Anne Mette Buhl
  • Karin Ekström Smedby
  • Henrik Hjalgrim
  • Ann-Christine Syvänen
  • Ake Borg
  • Anders Isaksson
  • Jesper Jurlander
  • Gunnar Juliusson
  • Richard Rosenquist
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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.

Original languageEnglish
JournalGenes, Chromosomes & Cancer
Volume47
Issue number8
Pages (from-to)697-711
Number of pages15
ISSN1045-2257
DOIs
Publication statusPublished - Aug 2008

    Research areas

  • Chromosomes, Artificial, Bacterial, Gene Dosage, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Loss of Heterozygosity, Microchip Analytical Procedures, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide

ID: 45731798