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ABSTRACT BACKGROUND: Prostate cancer (PCa) harbors a myriad of genomic and epigenetic defects. Cytosine methylation of CpG-rich promoter DNA is an important mechanism of epigenetic gene
inactivation in PCa. There is considerable amount of data to suggest that DNA methylation-based biomarkers may be useful for the early detection and diagnosis of PCa. In addition, candidate
gene-based studies have shown an association between specific gene methylation and alterations and clinicopathologic indicators of poor prognosis in PCa. METHODS: To more comprehensively
identify DNA methylation alterations in PCa initiation and progression, we examined the methylation status of 485 577 CpG sites from regions with a broad spectrum of CpG densities,
interrogating both gene-associated and non-associated regions using the recently developed Illumina 450K methylation platform. RESULTS: In all, we selected 33 promoter-associated novel CpG
sites that were differentially methylated in high-grade prostatic intraepithelial neoplasia and PCa in comparison with benign prostate tissue samples (false discovery rate-adjusted _P_-value
<0.05; _β_-value ⩾0.2; fold change >1.5). Of the 33 genes, hierarchical clustering analysis demonstrated _BNC_1, _FZD_1, _RPL_39L, _SYN_2, _LMX_1B, _CXXC_5, _ZNF_783 and _CYB_5R2 as
top candidate novel genes that are frequently methylated and whose methylation was associated with inactivation of gene expression in PCa cell lines. Pathway analysis of the genes with
altered methylation patterns identified the involvement of a cancer-related network of genes whose activity may be regulated by _TP_53, _MYC_, _TNF_, _IL_1 and 6, _IFN_-γ and FOS in prostate
pathogenesis. CONCLUSION: Our genome-wide methylation profile shows epigenetic dysregulation of important regulatory signals in prostate carcinogenesis. Access through your institution Buy
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cancer marker. _Clin Cancer Res_ 2004; 10: 4010–4014. Article CAS PubMed Google Scholar Download references ACKNOWLEDGEMENTS This work was supported by grant from Department of Defense
Program Idea Award; PC101996 to Bernard Kwabi-Addo. This work is also supported by the use of facilities at Howard University Department of Biochemistry and Molecular Biology, and Children’s
National Medical Center. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Children’s National Medical Center, Center for Genetic Medicine Research, Washington, DC, USA J M Devaney & S
Funda * Cancer Center, Howard University, Washington, DC, USA S Wang, J Long, D J Taghipour, P Furbert-Harris & B Kwabi-Addo * Department of Biochemistry and Molecular Biology, Howard
University, Washington, DC, USA S Wang, R Tbaishat & B Kwabi-Addo * Department of Microbiology, Howard University, Washington, DC, USA P Furbert-Harris * Department of Pathology and
Immunology, Baylor College of Medicine, Houston, TX, USA M Ittmann Authors * J M Devaney View author publications You can also search for this author inPubMed Google Scholar * S Wang View
author publications You can also search for this author inPubMed Google Scholar * S Funda View author publications You can also search for this author inPubMed Google Scholar * J Long View
author publications You can also search for this author inPubMed Google Scholar * D J Taghipour View author publications You can also search for this author inPubMed Google Scholar * R
Tbaishat View author publications You can also search for this author inPubMed Google Scholar * P Furbert-Harris View author publications You can also search for this author inPubMed Google
Scholar * M Ittmann View author publications You can also search for this author inPubMed Google Scholar * B Kwabi-Addo View author publications You can also search for this author inPubMed
Google Scholar CORRESPONDING AUTHOR Correspondence to B Kwabi-Addo. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no conflict of interest. RIGHTS AND PERMISSIONS Reprints and
permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Devaney, J., Wang, S., Funda, S. _et al._ Identification of novel DNA-methylated genes that correlate with human prostate cancer and
high-grade prostatic intraepithelial neoplasia. _Prostate Cancer Prostatic Dis_ 16, 292–300 (2013). https://doi.org/10.1038/pcan.2013.21 Download citation * Received: 07 March 2013 *
Revised: 24 June 2013 * Accepted: 27 June 2013 * Published: 30 July 2013 * Issue Date: December 2013 * DOI: https://doi.org/10.1038/pcan.2013.21 SHARE THIS ARTICLE Anyone you share the
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Nature SharedIt content-sharing initiative KEYWORDS * genome-wide DNA methylation analysis * pyrosequencing * gene expression