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.

Large but not small copy-number alterations correlate to high-risk genomic aberrations and survival in chronic lymphocytic leukemia: a high-resolution genomic screening of newly diagnosed patients

“…4,9 This discrepancy between different array studies is probably highly influenced by the differential design of microarrays applied. 8 Overall survival was investigated in relation to the hierarchal model of known recurrent alterations, which verified the clinical impact of these prognostic markers (Figure 2a). However, one exception to earlier studies was the similar disease course for del(11q) and trisomy 12 (Figure 2a).…”

“…8 All raw and normalized data from the SNP arrays can be accessed through Gene Expression Omnibus (http://www.ncbi.nlm.nih. gov/geo, accession number: GSE16406).…”

Molecular analysis reveals a genetic basis for the phenotypic diversity of metaplastic breast carcinomas

“…This type of BAC array platform has been shown to be as robust as, and to have comparable resolution with, high-density oligonucleotide arrays [25][26][27]. DNA labelling, array hybridizations and image acquisition were performed as previously described [28,29].…”

Genomic and immunohistochemical analysis of adenosquamous carcinoma of the breast

“…This type of BAC array platform has been shown to be as robust as and to have comparable resolution with high-density oligonucleotide arrays. [12][13][14] Labelling, hybridization, washes, image acquisition and data normalization were carried out as previously described. 11 The final data set comprised 31 367 clones with unambiguous mapping information according to the hg19 of the human genome (http://www.…”