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67th Annual Meeting Abstracts
Genomic Study On Prostate Cancer Disparities Associated With The African American Population
*Bi-Dar Wang, Ramez Andrawis, *Fernando J Bianco, Harold Fraizer, *James Tall, *Steven R Patierno, *Norman H Lee The George Washington University, Washington, DC
Introduction: African Americans (AA) have the highest risk of developing prostate cancer with aggressive disease compared to Caucasian Americans (CA). To identify the genetic predisposition and oncogenetic signatures, we applied genomic approaches to compare RNA expression profiles and DNA copy number variations (CNVs). Materials & Methods: Prostate cancer biopsy cores and adjacent benign cores from 6 AA and 4 CA were collected. The purified RNA and DNA samples were processed and hybridized onto Affymetrix Exon and SNP 6.0 arrays to examine the RNA expression profiles and DNA CNVs, respectively. Results: 95 genes were differentially expressed in the benign cores from normal AAs and CAs. These genes were selected for further clustering analysis and functional classification. These genes could be functionally classified into four major networks involving in ERK, NF-κB, insulin/INS1 signaling and androgen metabolism. Comparisons of the expression profiles from cancer with the adjacent benign tissues revealed that 289 differentially expressed genes were involved in the regulation of several oncogenic and inflammatory pathways in AA patients. STAT1 and RHOA genes were highly expressed in AA, suggesting the more aggressive tumor. Exon array results further revealed the alternative splicing variants in three genes associated with prostate cancer progression; including TMG4 and ESRRG in normal AA, and STAT1 in cancer AA. Conclusions: The exon and SNP profiling reveals differential expression patterns and CNVs in normal and cancer biopsies in two ethnic groups, suggesting that differences in inflammatory responses, oncogenic pathways, and insulin and androgen metabolisms may account for the observed disparities.
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