Email updates

Keep up to date with the latest news and content from BMC Urology and BioMed Central.

Open Access Highly Accessed Research article

Dysregulated methylation at imprinted genes in prostate tumor tissue detected by methylation microarray

Daniel I Jacobs1, Yingying Mao12, Alan Fu1, William Kevin Kelly3 and Yong Zhu1*

Author Affiliations

1 Yale School of Public Health, Yale University School of Medicine, New Haven, CT, USA

2 Department of Epidemiology and Health Statistics, Zhejiang University School of Public Health, Hangzhou, Zhejiang Province, China

3 Department of Medical Oncology and Urology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

For all author emails, please log on.

BMC Urology 2013, 13:37  doi:10.1186/1471-2490-13-37

Published: 26 July 2013

Abstract

Background

Imprinting is an important epigenetic regulator of gene expression that is often disrupted in cancer. While loss of imprinting (LOI) has been reported for two genes in prostate cancer (IGF2 and TFPI2), disease-related changes in methylation across all imprinted gene regions has not been investigated.

Methods

Using an Illumina Infinium Methylation Assay, we analyzed methylation of 396 CpG sites in the promoter regions of 56 genes in a pooled sample of 12 pairs of prostate tumor and adjacent normal tissue. Selected LOI identified from the array was validated using the Sequenom EpiTYPER assay for individual samples and further confirmed by expression data from publicly available datasets.

Results

Methylation significantly increased in 52 sites and significantly decreased in 17 sites across 28 unique genes (P < 0.05), and the strongest evidence for loss of imprinting was demonstrated in tumor suppressor genes DLK1, PLAGL1, SLC22A18, TP73, and WT1. Differential expression of these five genes in prostate tumor versus normal tissue using array data from a publicly available database were consistent with the observed LOI patterns, and WT1 hypermethylation was confirmed using quantitative DNA methylation analysis.

Conclusions

Together, these findings suggest a more widespread dysregulation of genetic imprinting in prostate cancer than previously reported and warrant further investigation.

Keywords:
Imprinting; Prostate cancer; Differential methylation; DLK1; PLAGL1; SLC22A18; TP73; WT1