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

Rose AE, Satagopan JM, Oddoux C, Zhou Q, Xu R, Olshen AB, Yu JZ, Dash A, Jean-Gilles J, Reuter V, Gerald WL, Lee P, Osman I - J Transl Med (2010)

Bottom Line: 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.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Urology, New York University School of Medicine, New York, New York 10016, USA.

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.

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Related in: MedlinePlus

Oligo-based aCGH of 28AA and 180CA prostate tumors revealed 23 unique chromosomal regions (represented by 36 probes) with significantly different (P ≤ 0.0001) DNA copy number.
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Figure 2: Oligo-based aCGH of 28AA and 180CA prostate tumors revealed 23 unique chromosomal regions (represented by 36 probes) with significantly different (P ≤ 0.0001) DNA copy number.

Mentions: In the larger ongoing study utilizing oligo-based aCGH, a total of 579 genomic regions exhibited copy number gains or losses in at least 10% of the AA and CA samples. We then compared the copy number changes in AA versus CA patients in these 579 regions and ranked the regions by increasing order of the p-values. The 23 most significantly altered regions (represented by 36 probes) with P-value ≤ 0.0001 are shown in Figure 2. Of these regions, 9 were more commonly lost in AA patients compared to CA patients (1q31.3, 1q44, 3q26.1, 4q13.2, 5q33.1, 7q35, 11p15.4, 17q21.31, and 20p13), while 12 showed significant gains in AA compared to CA patients (1p36.13, 5p15.33, 5q35.3, 8p11.23, 14q24.3, 14q32.33, 15q11.2, 16p11.2, 17q12, 17q21.32, 17q25.3, and 21p11.1). Two regions, 6p21.32 and 16q22.3 had both significant gains and losses in AA patients compared to CA. As in the BAC-based analysis, we did not find significant genomic alterations in chromosomes 2 or 19.


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

Rose AE, Satagopan JM, Oddoux C, Zhou Q, Xu R, Olshen AB, Yu JZ, Dash A, Jean-Gilles J, Reuter V, Gerald WL, Lee P, Osman I - J Transl Med (2010)

Oligo-based aCGH of 28AA and 180CA prostate tumors revealed 23 unique chromosomal regions (represented by 36 probes) with significantly different (P ≤ 0.0001) DNA copy number.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2913940&req=5

Figure 2: Oligo-based aCGH of 28AA and 180CA prostate tumors revealed 23 unique chromosomal regions (represented by 36 probes) with significantly different (P ≤ 0.0001) DNA copy number.
Mentions: In the larger ongoing study utilizing oligo-based aCGH, a total of 579 genomic regions exhibited copy number gains or losses in at least 10% of the AA and CA samples. We then compared the copy number changes in AA versus CA patients in these 579 regions and ranked the regions by increasing order of the p-values. The 23 most significantly altered regions (represented by 36 probes) with P-value ≤ 0.0001 are shown in Figure 2. Of these regions, 9 were more commonly lost in AA patients compared to CA patients (1q31.3, 1q44, 3q26.1, 4q13.2, 5q33.1, 7q35, 11p15.4, 17q21.31, and 20p13), while 12 showed significant gains in AA compared to CA patients (1p36.13, 5p15.33, 5q35.3, 8p11.23, 14q24.3, 14q32.33, 15q11.2, 16p11.2, 17q12, 17q21.32, 17q25.3, and 21p11.1). Two regions, 6p21.32 and 16q22.3 had both significant gains and losses in AA patients compared to CA. As in the BAC-based analysis, we did not find significant genomic alterations in chromosomes 2 or 19.

Bottom Line: 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.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Urology, New York University School of Medicine, New York, New York 10016, USA.

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.

Show MeSH
Related in: MedlinePlus