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  DNA–Methylome Analysis of Mouse Intestinal Adenoma Identifies a Tumour-Specific Signature That Is Partly Conserved in Human Colon Cancer

Grimm, C., Chavez, L., Vilardell, M., Farrall, A., Tierling, S., Böhm, J. W., et al. (2013). DNA–Methylome Analysis of Mouse Intestinal Adenoma Identifies a Tumour-Specific Signature That Is Partly Conserved in Human Colon Cancer. PLoS Genetics, 9(2), e1003250-e1003250. doi:10.1371/journal.pgen.1003250.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-E7A4-8 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-A9EC-3
Genre: Journal Article

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© 2013 Grimm et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Grimm, Christina1, Author              
Chavez, Lukas2, Author              
Vilardell, Mireia2, Author              
Farrall, Alexandra3, Author              
Tierling, Sascha4, Author
Böhm, Julia W.4, Author
Grote, Phillip3, Author              
Lienhard, Matthias5, Author              
Dietrich, Jörn1, Author
Timmermann, Bernd6, Author              
Walter, Jörn4, Author
Schweiger, Michal R.7, Author              
Lehrach, Hans2, Author              
Herwig, Ralf5, Author              
Herrmann, Bernhard G.3, Author              
Morkel, Markus3, Author              
Affiliations:
1In 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              
2Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, Berlin, Germany, ou_1433550              
3Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society, Berlin, Germany, ou_1433548              
4Universität des Saarlandes, FR 8.3 Biowissenschaften, Genetik/Epigenetik Campus, Saarbrücken, Germany, ou_persistent22              
5Bioinformatics (Ralf Herwig), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, Berlin, Germany, ou_1479648              
6Sequencing (Head: Bernd Timmermann), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479670              
7Cancer Genomics (Michal-Ruth Schweiger), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, Berlin, Germany, ou_1479649              

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 Abstract: Aberrant CpG methylation is a universal epigenetic trait of cancer cell genomes. However, human cancer samples or cell lines preclude the investigation of epigenetic changes occurring early during tumour development. Here, we have used MeDIP-seq to analyse the DNA methylome of APCMin adenoma as a model for intestinal cancer initiation, and we present a list of more than 13,000 recurring differentially methylated regions (DMRs) characterizing intestinal adenoma of the mouse. We show that Polycomb Repressive Complex (PRC) targets are strongly enriched among hypermethylated DMRs, and several PRC2 components and DNA methyltransferases were up-regulated in adenoma. We further demonstrate by bisulfite pyrosequencing of purified cell populations that the DMR signature arises de novo in adenoma cells rather than by expansion of a pre-existing pattern in intestinal stem cells or undifferentiated crypt cells. We found that epigenetic silencing of tumour suppressors, which occurs frequently in colon cancer, was rare in adenoma. Quite strikingly, we identified a core set of DMRs, which is conserved between mouse adenoma and human colon cancer, thus possibly revealing a global panel of epigenetically modified genes for intestinal tumours. Our data allow a distinction between early conserved epigenetic alterations occurring in intestinal adenoma and late stochastic events promoting colon cancer progression, and may facilitate the selection of more specific clinical epigenetic biomarkers.

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Language(s): eng - English
 Dates: 2013-02-07
 Publication Status: Published online
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: PMC: 3567140
DOI: 10.1371/journal.pgen.1003250
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Title: PLoS Genetics
Source Genre: Journal
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Publ. Info: San Francisco, USA : Public Library of Science
Pages: - Volume / Issue: 9 (2) Sequence Number: - Start / End Page: e1003250 - e1003250 Identifier: Other: PLoS Genet