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dc.contributor.authorPerry, A S
dc.contributor.authorLoftus, B
dc.contributor.authorMoroose, R
dc.contributor.authorLynch, T H
dc.contributor.authorHollywood, D
dc.contributor.authorWatson, R W G
dc.contributor.authorWoodson, K
dc.contributor.authorLawler, M
dc.date.accessioned2017-06-13T13:38:45Z
dc.date.available2017-06-13T13:38:45Z
dc.date.issued2007-05-21
dc.identifier.citationIn silico mining identifies IGFBP3 as a novel target of methylation in prostate cancer. 2007, 96 (10):1587-94 Br. J. Canceren
dc.identifier.issn0007-0920
dc.identifier.pmid17453001
dc.identifier.doi10.1038/sj.bjc.6603767
dc.identifier.urihttp://hdl.handle.net/10147/621425
dc.description.abstractPromoter hypermethylation is central in deregulating gene expression in cancer. Identification of novel methylation targets in specific cancers provides a basis for their use as biomarkers of disease occurrence and progression. We developed an in silico strategy to globally identify potential targets of promoter hypermethylation in prostate cancer by screening for 5' CpG islands in 631 genes that were reported as downregulated in prostate cancer. A virtual archive of 338 potential targets of methylation was produced. One candidate, IGFBP3, was selected for investigation, along with glutathione-S-transferase pi (GSTP1), a well-known methylation target in prostate cancer. Methylation of IGFBP3 was detected by quantitative methylation-specific PCR in 49/79 primary prostate adenocarcinoma and 7/14 adjacent preinvasive high-grade prostatic intraepithelial neoplasia, but in only 5/37 benign prostatic hyperplasia (P < 0.0001) and in 0/39 histologically normal adjacent prostate tissue, which implies that methylation of IGFBP3 may be involved in the early stages of prostate cancer development. Hypermethylation of IGFBP3 was only detected in samples that also demonstrated methylation of GSTP1 and was also correlated with Gleason score > or =7 (P=0.01), indicating that it has potential as a prognostic marker. In addition, pharmacological demethylation induced strong expression of IGFBP3 in LNCaP prostate cancer cells. Our concept of a methylation candidate gene bank was successful in identifying a novel target of frequent hypermethylation in early-stage prostate cancer. Evaluation of further relevant genes could contribute towards a methylation signature of this disease.
dc.language.isoenen
dc.relation.urlwww.bjcancer.comen
dc.rightsArchived with thanks to British journal of canceren
dc.subjectPROSTATE CANCERen
dc.subjectDIAGNOSISen
dc.subject.meshBase Sequence
dc.subject.meshComputational Biology
dc.subject.meshDNA Methylation
dc.subject.meshDatabases, Genetic
dc.subject.meshGene Expression Regulation, Neoplastic
dc.subject.meshGene Silencing
dc.subject.meshGlutathione S-Transferase pi
dc.subject.meshHumans
dc.subject.meshInsulin-Like Growth Factor Binding Protein 3
dc.subject.meshInsulin-Like Growth Factor Binding Proteins
dc.subject.meshMale
dc.subject.meshMolecular Sequence Data
dc.subject.meshPromoter Regions, Genetic
dc.subject.meshProstatic Intraepithelial Neoplasia
dc.subject.meshProstatic Neoplasms
dc.titleIn silico mining identifies IGFBP3 as a novel target of methylation in prostate cancer.en
dc.typeArticleen
dc.identifier.journalBritish journal of canceren
dc.description.fundingNo fundingen
dc.description.provinceLeinsteren
dc.description.peer-reviewpeer-reviewen
refterms.dateFOA2018-08-27T21:55:17Z
html.description.abstractPromoter hypermethylation is central in deregulating gene expression in cancer. Identification of novel methylation targets in specific cancers provides a basis for their use as biomarkers of disease occurrence and progression. We developed an in silico strategy to globally identify potential targets of promoter hypermethylation in prostate cancer by screening for 5' CpG islands in 631 genes that were reported as downregulated in prostate cancer. A virtual archive of 338 potential targets of methylation was produced. One candidate, IGFBP3, was selected for investigation, along with glutathione-S-transferase pi (GSTP1), a well-known methylation target in prostate cancer. Methylation of IGFBP3 was detected by quantitative methylation-specific PCR in 49/79 primary prostate adenocarcinoma and 7/14 adjacent preinvasive high-grade prostatic intraepithelial neoplasia, but in only 5/37 benign prostatic hyperplasia (P < 0.0001) and in 0/39 histologically normal adjacent prostate tissue, which implies that methylation of IGFBP3 may be involved in the early stages of prostate cancer development. Hypermethylation of IGFBP3 was only detected in samples that also demonstrated methylation of GSTP1 and was also correlated with Gleason score > or =7 (P=0.01), indicating that it has potential as a prognostic marker. In addition, pharmacological demethylation induced strong expression of IGFBP3 in LNCaP prostate cancer cells. Our concept of a methylation candidate gene bank was successful in identifying a novel target of frequent hypermethylation in early-stage prostate cancer. Evaluation of further relevant genes could contribute towards a methylation signature of this disease.


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