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    In silico mining identifies IGFBP3 as a novel target of methylation in prostate cancer.

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    Authors
    Perry, A S
    Loftus, B
    Moroose, R
    Lynch, T H
    Hollywood, D
    Watson, R W G
    Woodson, K
    Lawler, M
    Issue Date
    2007-05-21
    Keywords
    PROSTATE CANCER
    DIAGNOSIS
    MeSH
    Base Sequence
    Computational Biology
    DNA Methylation
    Databases, Genetic
    Gene Expression Regulation, Neoplastic
    Gene Silencing
    Glutathione S-Transferase pi
    Humans
    Insulin-Like Growth Factor Binding Protein 3
    Insulin-Like Growth Factor Binding Proteins
    Male
    Molecular Sequence Data
    Promoter Regions, Genetic
    Prostatic Intraepithelial Neoplasia
    Prostatic Neoplasms
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    Citation
    In silico mining identifies IGFBP3 as a novel target of methylation in prostate cancer. 2007, 96 (10):1587-94 Br. J. Cancer
    Journal
    British journal of cancer
    URI
    http://hdl.handle.net/10147/621425
    DOI
    10.1038/sj.bjc.6603767
    PubMed ID
    17453001
    Additional Links
    www.bjcancer.com
    Abstract
    Promoter 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.
    Item Type
    Article
    Language
    en
    ISSN
    0007-0920
    ae974a485f413a2113503eed53cd6c53
    10.1038/sj.bjc.6603767
    Scopus Count
    Collections
    St. Luke's Radiation Oncology Network, Dublin

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