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  Genome-wide DNA methylation events in TMPRSS2-ERG fusion-negative prostate cancers implicate an EZH2-dependent mechanism with miR-26a hypermethylation

Börno, S., Fischer, A., Kerick, M., Falth, M., Laible, M., Brase, J. C., et al. (2012). Genome-wide DNA methylation events in TMPRSS2-ERG fusion-negative prostate cancers implicate an EZH2-dependent mechanism with miR-26a hypermethylation. Cancer Discovery, 2(11), 1024-1035. doi:10.1158/2159-8290.CD-12-0041.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-F028-4 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-F029-2
Genre: Journal Article

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 Creators:
Börno, S.1, Author              
Fischer, A.1, Author              
Kerick, M.1, Author              
Falth, M., Author
Laible, M., Author
Brase, J. C., Author
Kuner, R., Author
Dahl, A., Author
Grimm, C.2, Author              
Sayanjali, B., Author
Isau, M.1, Author              
Röhr, C.1, Author              
Wunderlich, A.1, Author              
Timmermann, B.3, Author              
Claus, R., Author
Plass, C., Author
Graefen, M., Author
Simon, R., Author
Demichelis, F., Author
Rubin, M. A., Author
Sauter, G., AuthorSchlomm, T., AuthorSültmann, H., AuthorLehrach, H.4, Author              Schweiger, M. R.1, Author               more..
Affiliations:
1Cancer Genomics (Michal-Ruth Schweiger), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, Berlin, Germany, ou_1479649              
2In vitro Ligand Screening (Zoltán Konthur), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, Berlin, Germany, ou_1479653              
3Sequencing, Max Planck Institute for Molecular Genetics, Max Planck Society, Berlin, Germany, ou_1433559              
4Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, Berlin, Germany, ou_1433550              

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 Abstract: Prostate cancer is the second most common cancer among men worldwide. Alterations in the DNA methylation pattern can be one of the leading causes for prostate cancer formation. This study is the first high-throughput sequencing study investigating genome-wide DNA methylation patterns in a large cohort of 51 tumor and 53 benign prostate samples using methylated DNA immunoprecipitation sequencing. Comparative analyses identified more than 147,000 cancer-associated epigenetic alterations. In addition, global methylation patterns show significant differences based on the TMPRSS2-ERG rearrangement status. We propose the hypermethylation of miR-26a as an alternative pathway of ERG rearrangement-independent EZH2 activation. The observed increase in differential methylation events in fusion-negative tumors can explain the tumorigenic process in the absence of genomic rearrangements. SIGNIFICANCE: In contrast to TMPRSS2-ERG -rearranged tumors, the pathomechanism for gene fusion-negative tumors is completely unclear. Using a sequencing-based approach, our work uncovers significant global epigenetic alterations in TMPRSS2-ERG gene fusion-negative tumors and provides a mechanistic explanation for the tumor formation process.

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 Dates: 2012-08-282012-11
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1158/2159-8290.CD-12-0041
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Title: Cancer Discovery
Source Genre: Journal
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Pages: - Volume / Issue: 2 (11) Sequence Number: - Start / End Page: 1024 - 1035 Identifier: -