Copy number and gene expression differences between African American and Caucasian American prostate cancer
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RESEARCH
Copy number and gene expression differences between African American and Caucasian American prostate cancer Research
Amy E Rose1, Jaya M Satagopan2, Carole Oddoux3, Qin Zhou2, Ruliang Xu5, Adam B Olshen2, Jessie Z Yu1, Atreya Dash4, Jerome Jean-Gilles1, Victor Reuter6, William L Gerald6, Peng Lee*5 and Iman Osman*1
Abstract Background: The goal of our study was to investigate the molecular underpinnings associated with the relatively aggressive clinical behavior of prostate cancer (PCa) in African American (AA) compared to Caucasian American (CA) patients using a genome-wide approach. Methods: AA and CA patients treated with radical prostatectomy (RP) were frequency matched for age at RP, Gleason grade, and tumor stage. Array-CGH (BAC SpectralChip2600) was used to identify genomic regions with significantly different DNA copy number between the groups. Gene expression profiling of the same set of tumors was also evaluated using Affymetrix HG-U133 Plus 2.0 arrays. Concordance between copy number alteration and gene expression was examined. A second aCGH analysis was performed in a larger validation cohort using an oligo-based platform (Agilent 244K). Results: BAC-based array identified 27 chromosomal regions with significantly different copy number changes between the AA and CA tumors in the first cohort (Fisher's exact test, P < 0.05). Copy number alterations in these 27 regions were also significantly associated with gene expression changes. aCGH performed in a larger, independent cohort of AA and CA tumors validated 4 of the 27 (15%) most significantly altered regions from the initial analysis (3q26, 5p15-p14, 14q32, and 16p11). Functional annotation of overlapping genes within the 4 validated regions of AA/CA DNA copy number changes revealed significant enrichment of genes related to immune response. Conclusions: Our data reveal molecular alterations at the level of gene expression and DNA copy number that are specific to African American and Caucasian prostate cancer and may be related to underlying differences in immune response. Background African Americans (AA) have a higher incidence of prostate cancer (PCa) and a higher mortality from the disease compared to age-matched Caucasians (CA)[1-4]. It remains controversial, however, whether these inequalities are solely attributable to socio-economic variables or if genetic and/or molecular differences also play a significant role [5-10]. We previously reported that between * Correspondence: [email protected], [email protected] 1
Department of Urology, New York University School of Medicine, New York, New York 10016, USA 5 Department of Pathology, New York University School of Medicine, New York, New York 10016, USA ^ Deceased Full list of author information is available at the end of the article
1990 and 2000, the disparity between racial groups with regard to both pathologic stage and age at RP diminished significantly among patients treated at the Manhattan Veteran's Hospital, an equal access to care institution[11]. Disparity in
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