Simultaneously detection of genomic and expression alterations in prostate cancer using cDNA microarray.
BACKGROUND
Prostate cancer is a common disease among men but the knowledge of the prostate carcinogenesis is still limited.


METHODS
cDNA microarray-based comparative genomic hybridization (CGH) and expression profiling were performed to screen the genomic and the expression changes in prostate cancer respectively. The two data were integrated to study the influence of genomic aberrations on gene expression and seek for the genes with their expression affected by the genomic aberrations. Real-time PCR was performed to evaluate the array data.


RESULTS
Array-based CGH detected gains at 2q, 3p/q, 5q, 6q, 8q, 9p, 10p/q, 11q, 12p, 14q, and 19p/q and losses at 1p, 2p, 4q, 6p/q, 7p, 11p/q, 12q, 17p/q, 19p/q, and Xp/q in more than 20% prostate tumors and narrowed these aberrations. For example, the gain of 8q was mapped to five minimal regions. Novel aberrations were also identified, such as loss at Xq21.33-q22.2. Expression profiling discovered the significant biological processes involved in the prostate carcinogenesis, such as exogenous antigen presentation via MHC class II and protein ubiquitination. Integration analysis revealed a weak positive correlation between genomic copy number and gene expression level. Fifty-three genes showed their expression directly affected by the genomic aberrations possibly, including more than one member of Ras superfamily and major histocompatibility complex (MHC). These genes are involved in multiple biological processes.


CONCLUSIONS
Integration of the CGH and expression data provided more information than separate analysis. Although the direct influence of genomic aberrations on gene expression seems weak, the influence can be extended by indirect regulation through a few directly affected genes. Because the influence can be persistent, the genes directly affected by the genomic aberrations may play key roles in the prostate carcinogenesis and are worth further analysis.
Jiang
Mei
M
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, China.
Li
Ming
M
Fu
Xuping
X
Huang
Yan
Y
Qian
Hui
H
Sun
Ruping
R
Mao
Yumin
Y
Xie
Yi
Y
Li
Yao
Y
D002869:Chromosome Aberrations; D018628:Gene Dosage; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D006801:Humans; D008297:Male; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011471:Prostatic Neoplasms / Q000235:genetics*; D012334:RNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D015203:Reproducibility of Results; D018709:Statistics, Nonparametric
D012334:RNA, Neoplasm