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Genome-wide Loss of Heterozygosity Analysis from Laser Capture Microdissected Prostate Cancer Using Single Nucleotide Polymorphic Allele (SNP) Arrays and a Novel Bioinformatics Platform dChipSNP^{1 ,,2}

Departments of Medical Oncology [D. T., P. G. F., J. S., P. W. K., M. M., W. R. S.], Radiation Oncology [M. E. L.], and Biostatistical Sciences [C. L.], Dana-Farber Cancer Institute; Departments of Medicine [P. W. K., W. R. S.] and Pathology [M. Lec., M. Lod.], Brigham and Women’s Hospital; Departments of Medicine [P. G. F., P. W. K., W. R. S.] and Pathology [M. Lod., M. M.], Harvard Medical School; and Department of Biostatistics [M. Lin, C. L.], Harvard School of Public Health, Boston, Massachusetts 02115

Oligonucleotide arrays that detect single nucleotide polymorphisms were used to generate genome-wide loss of heterozygosity (LOH) maps from laser capture microdissected paraffin-embedded samples using as little as 5 ng of DNA. The allele detection rate from such samples was comparable with that obtained with standard amounts of DNA prepared from frozen tissues. A novel informatics platform, dChipSNP, was used to automate the definition of statistically valid regions of LOH, assign LOH genotypes to prostate cancer samples, and organize by hierarchical clustering prostate cancers based on the pattern of LOH. This organizational strategy revealed apparently distinct genetic subsets of prostate cancer.

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