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dc.contributor.authorPerry, Antoinette S
dc.contributor.authorO'Hurley, Gillian
dc.contributor.authorRaheem, Omer A
dc.contributor.authorBrennan, Kevin
dc.contributor.authorWong, Simon
dc.contributor.authorO'Grady, Anthony
dc.contributor.authorKennedy, Anne-Marie
dc.contributor.authorMarignol, Laure
dc.contributor.authorMurphy, Therese M
dc.contributor.authorSullivan, Linda
dc.contributor.authorBarrett, Ciara
dc.contributor.authorLoftus, Barbara
dc.contributor.authorThornhill, John
dc.contributor.authorHewitt, Stephen M
dc.contributor.authorLawler, Mark
dc.contributor.authorKay, Elaine
dc.contributor.authorLynch, Thomas
dc.contributor.authorHollywood, Donal
dc.date.accessioned2014-07-31T13:33:02Z
dc.date.available2014-07-31T13:33:02Z
dc.date.issued2013-04-15
dc.identifier.citationPerry AS et al. Gene expression and epigenetic discovery screen reveal methylation of SFRP2 in prostate cancer. Int. J. Cancer 2013, 132 (8):1771-80en_GB
dc.identifier.issn1097-0215
dc.identifier.pmid22915211
dc.identifier.doi10.1002/ijc.27798
dc.identifier.urihttp://hdl.handle.net/10147/324052
dc.description.abstractAberrant 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.
dc.language.isoenen
dc.rightsArchived with thanks to International journal of cancer. Journal international du canceren_GB
dc.subjectDNA Methylationen_GB
dc.subjectEpigenesis, Geneticen_GB
dc.subjectGene Expression Profilingen_GB
dc.subjectMembrane Proteins/geneticsen_GB
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshCell Line, Tumor
dc.subject.meshDNA Methylation
dc.subject.meshEpigenesis, Genetic
dc.subject.meshGene Expression Profiling
dc.subject.meshHumans
dc.subject.meshMale
dc.subject.meshMembrane Proteins
dc.subject.meshMiddle Aged
dc.subject.meshPromoter Regions, Genetic
dc.subject.meshProstatic Neoplasms
dc.subject.meshReal-Time Polymerase Chain Reaction
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction
dc.titleGene expression and epigenetic discovery screen reveal methylation of SFRP2 in prostate cancer.en_GB
dc.typeArticleen
dc.contributor.departmentProstate Molecular Oncology, Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, Ireland. aperry@tcd.ieen_GB
dc.identifier.journalInternational journal of cancer. Journal international du canceren_GB
dc.description.fundingNo fundingen
dc.description.provinceLeinsteren
dc.description.peer-reviewpeer-reviewen
refterms.dateFOA2018-08-24T14:09:36Z
html.description.abstractAberrant 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.


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