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BMC Urology
Published in: BMC Urology 1/2013

Open Access 01-12-2013 | Research article

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

Authors: Daniel I Jacobs, Yingying Mao, Alan Fu, William Kevin Kelly, Yong Zhu

Published in: BMC Urology | Issue 1/2013

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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.
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Metadata
Title
Dysregulated methylation at imprinted genes in prostate tumor tissue detected by methylation microarray
Authors
Daniel I Jacobs
Yingying Mao
Alan Fu
William Kevin Kelly
Yong Zhu
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Urology / Issue 1/2013
Electronic ISSN: 1471-2490
DOI
https://doi.org/10.1186/1471-2490-13-37

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