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Unstable chromosomes linked to less favorable response to RT and surgery in prostate cancer patients
Date:9/25/2013

Atlanta, September 25, 2013 -- Detailed evaluation of a prostate cancer tumor biopsy may predict treatment outcomes for image-guided radiation therapy (IGRT) or surgery for prostate cancer, according to research presented today at the American Society for Radiation Oncology's (ASTRO's) 55th Annual Meeting. The study results indicate that patients who have abnormal levels of breaks at common fragile sites (CFSs), sites within the chromosomes that are sensitive to DNA damage, are more likely to have their cancer to return -- treatment failure. These CFS break abnormalities are usually associated with instability of the cell's DNA, a phenomenon that is particularly associated with cancer.

In this study, researchers assessed the outcomes of 280 prostate cancer (Cap) patients, and reviewed the DNA "fingerprints" of each patient's tumor (using the patient's initial diagnostic core biopsy) to determine if gene copy number alterations (CNAs), or breaks in CFSs, were related to a less positive response to treatment. Two groups were analyzed: 126 localized intermediate risk CaP patients who had received image-guided radiation therapy (IGRT) treatments, with a mean dose of 74.6 Gy; and 154 localized intermediate and high risk CaP patients who had undergone radical prostatectomy (RP), which is the surgical removal of the entire prostate gland.

Utilizing an array comparative genomic hybridization (aCGH), DNA from frozen needle biopsies of the RT patients was analyzed for 13 previously characterized CFSs: FRA2G, FRA3B, FRA4F, FRA6E, FRA6F, FRA7E, FRA7G, FRA7H, FRA7I, FRA7K, FRA8C, FRA9E, FRA16D. The effect of having at least one CNA in any CFS was assessed using the Kaplan-Meier method and Cox proportional hazard models.

The data revealed a pattern in which the patients who failed treatment had abnormal levels of CNAs at CFSs. In the IGRT group, CNAs in CFSs occurred frequently, with 80 of the patients (64 percent) having a CNA in one or more CF
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Contact: Michelle Kirkwood
michellek@astro.org
703-286-1600
American Society for Radiation Oncology
Source:Eurekalert

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