Discovery of novel hypermethylated genes in prostate cancer using genomic CpG island microarrays.

<h4>Background</h4>Promoter and 5' end methylation regulation of tumour suppressor genes is a common feature of many cancers. Such occurrences often lead to the silencing of these key genes and thus they may contribute to the development of cancer, including prostate cancer.<h4&g...

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Autores principales: Ken Kron, Vaijayanti Pethe, Laurent Briollais, Bekim Sadikovic, Hilmi Ozcelik, Alia Sunderji, Vasundara Venkateswaran, Jehonathan Pinthus, Neil Fleshner, Theodorus van der Kwast, Bharati Bapat
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2009
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Acceso en línea:https://doaj.org/article/e9ba6c2751a745b695ff910ae1046bd1
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Sumario:<h4>Background</h4>Promoter and 5' end methylation regulation of tumour suppressor genes is a common feature of many cancers. Such occurrences often lead to the silencing of these key genes and thus they may contribute to the development of cancer, including prostate cancer.<h4>Methodology/principal findings</h4>In order to identify methylation changes in prostate cancer, we performed a genome-wide analysis of DNA methylation using Agilent human CpG island arrays. Using computational and gene-specific validation approaches we have identified a large number of potential epigenetic biomarkers of prostate cancer. Further validation of candidate genes on a separate cohort of low and high grade prostate cancers by quantitative MethyLight analysis has allowed us to confirm DNA hypermethylation of HOXD3 and BMP7, two genes that may play a role in the development of high grade tumours. We also show that promoter hypermethylation is responsible for downregulated expression of these genes in the DU-145 PCa cell line.<h4>Conclusions/significance</h4>This study identifies novel epigenetic biomarkers of prostate cancer and prostate cancer progression, and provides a global assessment of DNA methylation in prostate cancer.