Genomic Approach to Identifying Novel Targets for Early Detection and Intervention of Prostate Cancer

摘要

Early detection and intervention are key to a favorable prognosis in prostate cancer. Despite advances in the detection and treatment of prostate cancer, the mortality rate remains high. To improve survival, early detection and treatment strategies tailored to pre-invasive prostate cancer are required. The authors propose to catalog genetic alterations associated with the developmental stages of disease for use as diagnostic tools, and to identify the critical genes that drive the transformation of premalignant lesions to tumors for use as molecular targets for novel treatment design. The combination of laser capture microdissection (efficient isolation of specific cell types from hundreds of specimens) and SMAL DNA fingerprinting technology (high- throughput analysis of genomic targets using minute quantities of DNA yielded from the microdissected cells) will facilitate systematic comparison of samples in various stages of disease development. By the end of this work, the authors will have identified a set of genetic loci (and genes) by virtue of their frequency of alteration in premalignant lesions and subsequently in low-grade tumors. They will have established a publicly accessible 'genetic alterations in prostate cancer' database that catalogs somatic changes present in the various stages of cancer progression. This information will contribute to the fundamental understanding of prostate cancer pathogenesis.