title: Dysregulated methylation at imprinted genes in prostate tumor tissue detected by methylation microarray.
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.
authors.affiliation: Yale School of Public Health, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Jacobs
authors.forename: Yingying
authors.initials: Y
authors.lastname: Mao
authors.forename: Alan
authors.initials: A
authors.lastname: Fu
authors.forename: William Kevin
authors.initials: WK
authors.lastname: Kelly
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D001483:Base Sequence; D019175:DNA Methylation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins
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