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

Publication/Presentation Date

7-26-2013

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.

Volume

13

First Page

37

Last Page

37

ISSN

1471-2490

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

23890537

Department(s)

Administration and Leadership

Document Type

Article

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