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Methods

High-resolution copy number analysis of paraffin-embedded archival tissue using SNP BeadArrays

¹ Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; ² Department of Medical Statistics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; ³ Department of Molecular Cell Biology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; ⁴ Complex Genetics Section, DBG-Department of Medical Genetics, University Medical Centre, 3508 AB Utrecht, The Netherlands

High-density SNP microarrays provide insight into the genomic events that occur in diseases like cancer through their capability to measure both LOH and genomic copy numbers. Where currently available methods are restricted to the use of fresh frozen tissue, we now describe the design and validation of copy number measurements using the Illumina BeadArray platform and the application of this technique to formalin-fixed, paraffin-embedded (FFPE) tissue. In fresh frozen tissue from a set of colorectal tumors with numerous chromosomal aberrations, our method measures copy number patterns that are comparable to values from established platforms, like Affymetrix GeneChip and BAC array-CGH. Moreover, paired comparisons of fresh frozen and FFPE tissues showed nearly identical patterns of genomic change. We conclude that this method enables the use of paraffin-embedded material for research into both LOH and numerical chromosomal abnormalities. These findings make the large pathological archives available for genomic analysis, which could be especially relevant for hereditary disease where fresh material from affected relatives is rarely available.

E-mail j.oosting{at}lumc.nl; fax 31-71-5248158.

[Supplemental material is available online at www.genome.org. The R-package BeadArray SNP used to perform the analysis is available from http://www.bioconductor.org. The data sets are available from the Gene Expression Omnibus with accession number GSE5347 [NCBI GEO] (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE5347).]

Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.5686107

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