High-Resolution Mapping of Structural Mutations in Prostate Cancer With Single Nucleotide Polymorphism Arrays
Annual summary rept. 1 Nov 2004-31 Oct 2005
DANA-FARBER CANCER INST BOSTON MA
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The proposal focused on the systematic mapping of large-scale genetic alterations in prostate cancer, and relating these mutations to prostate cancer progression. To that end, the proposal suggested the application of single nucleotide polymorphism SNP array technology to characterize large-scale genetic alterations in the prostate cancer genome. In the 11 months since the beginning of the award, significant progress has been made in all 3 specific aims. Multiple primary and metastatic prostate tumors have been collected and genome-wide maps loss of heterozygosity and copy number changes have been generated from 100K SNP array data. Regions of significant chromosomal aberrations have been identified, and in this preliminary analysis several of these aberrations have been found to correlate with prostate cancer progression. Unanticipated difficulties have arisen with laser capture microdissection of primary prostate cancers, however, and efforts are ongoing to surmount these difficulties. During the conduct of this research, a method for determination of loss of heterozygosity without the use of paired normals, was developed to account for the haplotype structure of the genome, and a manuscript describing this method is in review.
- Medicine and Medical Research