Objective: Single nucleotide polymorphism analysis (SNP) has recently been proposed as an alternative technique to comparative genomic hybridization (CGH) for defining loss of heterozygosity and gene copy number changes in a single experimental setup. In order to assess the potential of SNP analysis to complement or, ultimately, substitute CGH results, we applied both techniques to five primary tumor samples and two tumor cell lines. This was complemented by dilution experiments based on normal lymphocyte DNA to decipher the lower detection limit for genetic alterations.
Methods/results: Using an in-house software tool, we demonstrated that SNP analysis permits the generation of chromosomal alteration patterns that largely resemble conventional CGH ratio profiles of a given tumor/cell line. Moreover, compared to CGH, our SNP software tool allows a much more detailed definition of amplicon sizes and involved candidate genes. This advantage even persisted when the technique was applied to DNA with more than 60% of nontumor content. However, the detection of chromosomal losses is severely hampered by the presence of nontumor DNA so that the use of the SNP technique should be limited to tumor samples with more than 80% tumor DNA.
Conclusion: SNP analysis is a very valuable tool for the detection and characterization of high-level chromosomal amplifications in the vast majority of primary tumor samples. Our software tool improves the analysis of SNP data and the presentation of the results, bridging the gap to existing CGH knowledge (http://bioinformatics.uni-muenster.de, 'Publications and Supplements').