Dysregulated methylation at imprinted genes in prostate tumor tissue detected by methylation microarray.
BMC Urol
; 13: 37, 2013 Jul 26.
Article
em En
| MEDLINE
| ID: mdl-23890537
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Regulação Neoplásica da Expressão Gênica
/
Impressão Genômica
/
Metilação de DNA
/
Análise de Sequência com Séries de Oligonucleotídeos
/
Proteínas de Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
/
Male
Idioma:
En
Revista:
BMC Urol
Assunto da revista:
UROLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos