CNA profiling using high-density DNA methylation arrays (SNP array)

The integration of genomic and epigenomic data is becoming increasingly popular as we try to gain better understanding of the complex mechanisms driving the development and progression of cancer. However, this results in increased cost and sample depletion, the latter being particularly important when considering intra-tumour heterogeneity. We therefore sought to investigate the possible utility of high-density DNA methylation arrays to assess both aberrant methylation as well as changes in gene copy number. Comparing CN (Copy Number) data derived from the Infinium Human Methylation 450K arrays with that generated on SNP arrays, we demonstrate the utility of the Infinium arrays to detect single copy alterations as well as homozygous deletions and high level amplification with the reliability of current gold standard platforms. Furthermore, we show that the gene centric design of the Infinium methylation arrays allows identification of small single gene alterations, which would not be detected using standard SNP array analysis. These results show that Infinium 450K methylation arrays provide a robust and economic platform for detecting copy number and methylation changes in a single experiment. The ability to integrate such data from the same sample is critical for cancer research and will improve our understanding of how complex genomic and epigenomic interactions are driving the development and progression of a malignant phenotype. Extracted DNA from each sample was hybridised to Illumina CytoSNP12 v2.1 BeadChips.