Future Perspective

Extraordinary advances in SNP array technology and copy number analysis tools have been made over the past few years. SNP array technology is fast becoming an indispensable tool for discovering new tumor aberrations in gene copy numbers. More importantly, determining the relationship between gene copy number aberrations and drug responses, tumor progression, and other clinical data will provide a basis for individualized medicine, as has already been demonstrated in a few studies (59,60,61). The integration of large-scale copy number aberrations with gene expression profiles will facilitate the interpretation of gene expression data.

Whether a gene is considered up-regulated or down-regulated in tumor samples frequently depends on the reference chosen (62). The relationship between the copy number gain or loss and gene expression will thus provide a molecular basis for the interpretation of up-regulation or down-regulation of gene expression in tumors. However, large-scale copy number variations must be considered in the interpretation of tumor aberrations in gene copy numbers.

Common deletion polymorphisms (63, 64) and large-scale copy number variations (65, 66, 67, 68, 69) have been identified in normal human genomes. As a result, when normal DNA from a patient is not available, gene copy number aberrations detected in tumor DNA may include gene copy number variations that already exist in the normal population. In the future, the integration of gene expression data and DNA copy number aberrations will facilitate the identification of prognostic, diagnostic, and therapeutic targets for various tumors.

The use of SNP arrays to analyze low-quality DNA from FFPE tissue is still challenging and will continue to be an important area of ongoing research. An alternative high-throughput genotyping method that uses Illumina BeadArrays to detect tumor aberrations in gene copy numbers is currently being developed (70, 71, 72, 73, 74) and seems promising. A recent study demonstrated the utility of BeadArrays to generate identical genotypes as well as LOH/allelic imbalances from both FFPE and frozen tumor tissues (71). Furthermore, the LOH profiles of the BeadArrays were identical to those obtained by Affymetrix GeneChip 10 K arrays.

Currently, three high-density SNP genotyping BeadChips are available: the Sentrix Human-1 Genotyping BeadChip, which contains more than 109 K exon-centric SNPs; the HumanHap300 BeadChip, which contains more than 317 K tagged SNPs; and the HumanHap550 BeadChip, which contains more than 550 K tagged SNPs (73). Until whole-genome sequencing of the 3 billion base pairs of tumor genomes becomes more affordable, high-throughput, and of high quality, SNP arrays or the BeadChip will remain the most cost-effective ways to detect tumor samples with LOH and copy number aberrations in a genome scale.

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