Copy number and gene expression differences between African American and Caucasian American prostate cancer

Amy E Rose,Peng Lee,Atreya Dash,Victor Reuter,Jaya M Satagopan,Jessie Z Yu,Jerome Jean-Gilles,Adam B Olshen,Iman Osman,William L Gerald,Ruliang Xu,Qin Zhou,Carole Oddoux

doi:10.1186/1479-5876-8-70

Abstract

BackgroundThe 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.MethodsAA 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).ResultsBAC-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.ConclusionsOur 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.

Highlights

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
Both of our investigations as well as those by other groups showing differences in gene expression and single nucleotide polymorphisms in genes related to the androgen receptor[13,14,15,16], growth factors[17,18,19], and apoptosis[20] support the possibility that disparities in outcome between AA and CA PCa patients may have an underlying molecular or genetic component
An improved understanding of these alterations is a prerequisite for the development of effective, patient-specific, molecularly targeted therapy for both patient groups. We examined both DNA copy number changes and gene expression profiles in a cohort of AA and CA PCa patients using bacterial artificial chromosome (BAC)-based array comparative genomic hybridization, oligo-based aCGH, and gene expression array

Summary

Introduction

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. Our data suggest that socioeconomic factors play a limited role in PSA recurrence among AA men treated with RP[12] Both of our investigations as well as those by other groups showing differences in gene expression and single nucleotide polymorphisms in genes related to the androgen receptor[13,14,15,16], growth factors[17,18,19], and apoptosis[20] support the possibility that disparities in outcome between AA and CA PCa patients may have an underlying molecular or genetic component

Objectives

Methods

Results

Conclusion