Evaluation of high-resolution microarray platforms for genomic profiling of bone tumours

DNA from two different cytogenetically well-characterized bone sarcoma cell lines, representing a simple and a complex karyotype, respectively, was tested in duplicate on four high-resolution microarray platforms; Affymetrix Genome-Wide Human SNP Array 6.0, Agilent Human Genome CGH 244A, Illumina HumanExon510s-duo and Nimblegen HG18 CGH 385 k WG tiling v1.0. The data was analysed using the platform-specific analysis software, as well as a platform-independent analysis algorithm. DNA copy number was measured at six specific chromosomes or chromosomal regions, and compared with the expected ratio based on available cytogenetic information. All platforms performed well in terms of reproducibility and were able to delimit and score small amplifications and deletions at similar resolution, but Agilent microarrays showed better linearity and dynamic range. The platform-specific analysis software provided with each platform identified in general correct copy numbers, whereas using a platform-independent analysis algorithm, correct copy numbers were determined mainly for Agilent and Affymetrix microarrays.All platforms performed reasonably well, but Agilent microarrays showed better dynamic range, and like Affymetrix microarrays performed well with the platform-independent analysis software, implying more robust data. Bone tumours like osteosarcomas are heterogeneous tumours with complex karyotypes that may be difficult to interpret, and it is of importance to be able to well separate the copy number levels and detect copy number changes in subpopulations. Taking all this into consideration, the Agilent and Affymetrix microarray platforms were found to be a better choice for mapping DNA copy numbers in bone tumours, the latter having the advantage of also providing heterozygosity information.Chromosomal aberrations are frequent in cancer, and change in gene dosage is a common mechanism for activation or attenuation of oncogenes and tumour suppressor genes, respectively. In