The presence of the FRA12E/SMRT fragile site in the genome of prostate cancer patients is a predictor of metastatic development

A60

Background: The Silencing Mediator of Retinoic Acid and Thyroid Hormone Receptor (SMRT) gene that maps at chromosome 12q24 is a transcriptional co-repressor. Based on previous experiments in our Laboratory, we determined that prostate cancer cell lines and samples from prostate cancer patients with advanced disease have altered SMRT expression. We mapped a fragile site (FRA12E) within the SMRT gene. We hypothesized that patients with metastatic CaP have a higher incidence of FRA12E in their genome.Material and Methods: Blood samples were collected from 14 healthy men, 14 prostate cancer patients with no evidence of disease >5 years from diagnosis, and 14 men with metastatic CaP. Each sample was set in culture in the presence of aphidicoline (an inducer of fragile sites); chromosomes were harvested and fixed using classical cytogenetic techniques. SMRT-specific BAC clones were used in fluorescence in-situ hybridization (FISH) experiments using the patient's metaphase chromosomes. Images were collected, scored, and analyzed for a disrupted FISH signal indicative of FRA12E presence. Clinical data were also recorded.Results: The results of this pilot study showed that 1/14 healthy individual was carrier of the FRA12E fragile site, none of the patients with no evidence of disease >5 years from their primary diagnostic were carrier of the fragile site whereas all the patients with spread disease studied were carrier.Discussion: This pilot study examines the incidence of FRA12E in the genome of prostate cancer patients and suggests that the presence of FRA12E may be a useful predictor for the development of metastatic disease. Larger studies are underway to validate this potentially powerful metastatic predictor.