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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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BAC-based aCGH of 20 AA and 21 CA prostate tumors revealed 27 significantly altered genomic regions between the two groups.
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Figure 1: BAC-based aCGH of 20 AA and 21 CA prostate tumors revealed 27 significantly altered genomic regions between the two groups.

Mentions: In the initial cohort of 20AA and 21 CA, BAC-based array CGH revealed 27 noteworthy regions that displayed differences in copy number variations between AA and CA tumors (Figure 1). Of these, 10 regions (3q25-q26, 3q28-q29, 4p14-p12, 9q21, 10q11, 11q14, 12p13, 14q12, 16p11, 20p11-20q11) were more commonly altered in AA patients compared to CA. 15 regions were more commonly altered in CA patients (1p21-p13, 3p26-p25, 3q26, 5q12, 6q21, 8q13, 9q31, 14q32, 15q26, 15q13-q14, 15q24, 17p13, 18p11, 20q13, 22q11), and 2 regions (5p15-p14 and 13q34) were significantly altered in both groups but in different directions. We did not observe any significant changes between the 2 groups on chromosome 2,7,19, or 21.


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)

BAC-based aCGH of 20 AA and 21 CA prostate tumors revealed 27 significantly altered genomic regions between the two groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: BAC-based aCGH of 20 AA and 21 CA prostate tumors revealed 27 significantly altered genomic regions between the two groups.
Mentions: In the initial cohort of 20AA and 21 CA, BAC-based array CGH revealed 27 noteworthy regions that displayed differences in copy number variations between AA and CA tumors (Figure 1). Of these, 10 regions (3q25-q26, 3q28-q29, 4p14-p12, 9q21, 10q11, 11q14, 12p13, 14q12, 16p11, 20p11-20q11) were more commonly altered in AA patients compared to CA. 15 regions were more commonly altered in CA patients (1p21-p13, 3p26-p25, 3q26, 5q12, 6q21, 8q13, 9q31, 14q32, 15q26, 15q13-q14, 15q24, 17p13, 18p11, 20q13, 22q11), and 2 regions (5p15-p14 and 13q34) were significantly altered in both groups but in different directions. We did not observe any significant changes between the 2 groups on chromosome 2,7,19, or 21.

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