A DNA methylation microarray-based study identifies ERG as a gene commonly methylated in prostate cancer

被引：15

作者：

Schwartzman, Jacob ^{[1
]}

Mongoue-Tchokote, Solange ^{[2
,5
]}

Gibbs, Angela ^{[1
]}

Gao, Lina ^{[1
]}

Corless, Christopher L. ^{[2
,3
]}

Jin, Jennifer ^{[1
]}

Zarour, Luai ^{[1
]}

Higano, Celestia ^{[4
]}

True, Lawrence D. ^{[4
]}

Vessella, Robert L. ^{[4
]}

Wilmot, Beth ^{[2
,5
]}

Bottomly, Daniel ^{[2
,5
]}

McWeeney, Shannon K. ^{[2
,5
]}

Bova, G. Steven ^{[6
]}

Partin, Alan W. ^{[7
]}

Mori, Motomi ^{[2
,5
]}

Alumkal, Joshi J. ^{[1
,2
]}

机构：

[1] Div Hematol & Oncol, Portland, OR USA

[2] Oregon Clin & Translat Res Inst, Portland, OR USA

[3] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA

[4] Univ Washington, Med Ctr, Seattle, WA 98195 USA

[5] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Div Bioinformat & Computat Biol, Portland, OR 97201 USA

[6] Johns Hopkins Univ, James Buchanan Brady Urol Inst, Dept Pathol, Baltimore, MD USA

[7] Johns Hopkins Univ, James Buchanan Brady Urol Inst, Dept Urol & Oncol, Baltimore, MD USA

来源：

EPIGENETICS | 2011年 / 6卷 / 10期

基金：

美国国家卫生研究院;

关键词：

DNA methylation; prostate cancer; ERG; biomarker; polycomb; CHROMATIN PATTERN; CPG ISLANDS; HYPERMETHYLATION; TMPRSS2-ERG; POLYCOMB; FUSION; CELLS; ASSOCIATION; PROGRESSION; EXPRESSION;

D O I：

10.4161/epi.6.10.17727

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 1,505 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.

引用

页码：1248 / 1256

页数：9

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