Analysis of Preneoplasia Associated with Progression to Prostatic Cancer

摘要

PURPOSE: To examine the topographical variation in expression levels of genes associated with prostate cancer, telomere dysfunction and/or chromosomal instability. SCOPE: To show that telomere erosion observed in prostatic epithelium may involve DNA damage response/repair pathways at the onset of preneoplasia (HPIN) and cancer in me n. MAJ0R FINDINGS: Our working hypothesis is that cells that undergo telomere loss as part of the normal aging process in the prostate are more susceptible to undergo chromosome end-fusion thus triggering genomic instability. Our initial progress showed that loss of telomere length occurred in preneoplastic HPIN lesions that were located close to small, localized microfoci of newly diagnosed prostate cancer. We have optimized whole genome and RNA amplification techniques and shown that there is high fidelity and reproducibility of dissected amplified PCR product. RESULTS: The first phase of gene expression profiling in HPIN, and cancer foci using repair/damage response array has been successfully performed. We are developing topographical maps of telomere bass, genomic instability and concomitant changes in gene expression. SIGNIFICANCE: These results will form the first direct link between telomere-dependent alteration, DNA repair and damage response signaling in prostate cancer.