Gene expression and epigenetic discovery screen reveal methylation of SFRP2 in prostate cancer.
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Perry et al (IJC-2013) pre-pub ...
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Authors
Perry, Antoinette SO'Hurley, Gillian
Raheem, Omer A
Brennan, Kevin
Wong, Simon
O'Grady, Anthony
Kennedy, Anne-Marie
Marignol, Laure
Murphy, Therese M
Sullivan, Linda
Barrett, Ciara
Loftus, Barbara
Thornhill, John
Hewitt, Stephen M
Lawler, Mark
Kay, Elaine
Lynch, Thomas
Hollywood, Donal
Affiliation
Prostate Molecular Oncology, Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, Ireland. aperry@tcd.ieIssue Date
2013-04-15Keywords
DNA MethylationEpigenesis, Genetic
Gene Expression Profiling
Membrane Proteins/genetics
MeSH
AdultAged
Cell Line, Tumor
DNA Methylation
Epigenesis, Genetic
Gene Expression Profiling
Humans
Male
Membrane Proteins
Middle Aged
Promoter Regions, Genetic
Prostatic Neoplasms
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
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Perry AS et al. Gene expression and epigenetic discovery screen reveal methylation of SFRP2 in prostate cancer. Int. J. Cancer 2013, 132 (8):1771-80Journal
International journal of cancer. Journal international du cancerDOI
10.1002/ijc.27798PubMed ID
22915211Abstract
Aberrant activation of Wnts is common in human cancers, including prostate. Hypermethylation associated transcriptional silencing of Wnt antagonist genes SFRPs (Secreted Frizzled-Related Proteins) is a frequent oncogenic event. The significance of this is not known in prostate cancer. The objectives of our study were to (i) profile Wnt signaling related gene expression and (ii) investigate methylation of Wnt antagonist genes in prostate cancer. Using TaqMan Low Density Arrays, we identified 15 Wnt signaling related genes with significantly altered expression in prostate cancer; the majority of which were upregulated in tumors. Notably, histologically benign tissue from men with prostate cancer appeared more similar to tumor (r = 0.76) than to benign prostatic hyperplasia (BPH; r = 0.57, p < 0.001). Overall, the expression profile was highly similar between tumors of high (≥ 7) and low (≤ 6) Gleason scores. Pharmacological demethylation of PC-3 cells with 5-Aza-CdR reactivated 39 genes (≥ 2-fold); 40% of which inhibit Wnt signaling. Methylation frequencies in prostate cancer were 10% (2/20) (SFRP1), 64.86% (48/74) (SFRP2), 0% (0/20) (SFRP4) and 60% (12/20) (SFRP5). SFRP2 methylation was detected at significantly lower frequencies in high-grade prostatic intraepithelial neoplasia (HGPIN; 30%, (6/20), p = 0.0096), tumor adjacent benign areas (8.82%, (7/69), p < 0.0001) and BPH (11.43% (4/35), p < 0.0001). The quantitative level of SFRP2 methylation (normalized index of methylation) was also significantly higher in tumors (116) than in the other samples (HGPIN = 7.45, HB = 0.47, and BPH = 0.12). We show that SFRP2 hypermethylation is a common event in prostate cancer. SFRP2 methylation in combination with other epigenetic markers may be a useful biomarker of prostate cancer.Item Type
ArticleLanguage
enISSN
1097-0215ae974a485f413a2113503eed53cd6c53
10.1002/ijc.27798
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