Using DNA probes generated by chromosome microdissection, cDNA microarray analysis, and CGH findings, we have identified a series of chromosomal regions involved in human breast, ovarian and prostate cancer as well as other benign and malignant diseases. In order to isolate candidate target genes from these regions, we have developed technologies based on chromosome microdissection, and integrated genome mapping, including DNA microarray analysis. These technologies are being utilized to isolate candidate genes from amplified regions in breast cancer, ovarian cancer, sarcomas and other diseases. The methodology previously described illustrates the importance of developing rapid techniques for the identification of genes amplified in a series of key human tumors. In addition to recognizing known sites of gene amplification, we have identified several previously unidentified genes. We are currently focusing on breast cancer where current technologies are providing new insights into the chromosome aberrations which occur during tumor progression. Candidate chromosome regions and genes contained within them are being identified. The mechanism of action of candidate genes will be studied with model systems based on gene transfer, gene inactivation, and biochemical techniques. In addition, we are developing a comprehensive database of amplified chromosomal regions in soft tissue and bone sarcomas using microarray based CGH. As this technology has matured, we have begun to explore its application to the detection of regions of loss in cancer and to the identification of constitutional chromosome anomalies. This is a powerful approach for the identification of genes playing a causal role in disease genesis or progression and may provide novel prognostic markers as well as therapeutic targets.
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