title: A DNA methylation microarray-based study identifies ERG as a gene commonly methylated in prostate cancer.
abstract: DNA methylation of promoter regions is a common event in prostate cancer, one of the most common cancers in men worldwide. Because prior reports demonstrating that DNA methylation is important in prostate cancer studied a limited number of genes, we systematically quantified the DNA methylation status of 1505 CpG dinucleotides for 807 genes in 78 paraffin-embedded prostate cancer samples and three normal prostate samples. The ERG gene, commonly repressed in prostate cells in the absence of an oncogenic fusion to the TMPRSS2 gene, was one of the most commonly methylated genes, occurring in 74% of prostate cancer specimens. In an independent group of patient samples, we confirmed that ERG DNA methylation was common, occurring in 57% of specimens, and cancer-specific. The ERG promoter is marked by repressive chromatin marks mediated by polycomb proteins in both normal prostate cells and prostate cancer cells, which may explain ERG's predisposition to DNA methylation and the fact that tumors with ERG DNA methylation were more methylated, in general. These results demonstrate that bead arrays offer a high-throughput method to discover novel genes with promoter DNA methylation such as ERG, whose measurement may improve our ability to more accurately detect prostate cancer.
authors.affiliation: Division of Hematology/Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Schwartzman
authors.forename: Solange
authors.initials: S
authors.lastname: Mongoue-Tchokote
authors.forename: Angela
authors.initials: A
authors.lastname: Gibbs
authors.forename: Lina
authors.initials: L
authors.lastname: Gao
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Corless
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jin
authors.forename: Luai
authors.initials: L
authors.lastname: Zarour
authors.forename: Celestia
authors.initials: C
authors.lastname: Higano
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: True
authors.forename: Robert L
authors.initials: RL
authors.lastname: Vessella
authors.forename: Beth
authors.initials: B
authors.lastname: Wilmot
authors.forename: Daniel
authors.initials: D
authors.lastname: Bottomly
authors.forename: Shannon K
authors.initials: SK
authors.lastname: McWeeney
authors.forename: G Steven
authors.initials: GS
authors.lastname: Bova
authors.forename: Alan W
authors.initials: AW
authors.lastname: Partin
authors.forename: Motomi
authors.initials: M
authors.lastname: Mori
authors.forename: Joshi
authors.initials: J
authors.lastname: Alumkal
mesh_terms: D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics*; D012008:Recurrence; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG
chemical_list: C072312:ERG protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG