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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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© 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, Autor           
Chavez, Lukas2, Autor           
Vilardell, Mireia2, Autor           
Farrall, Alexandra3, Autor           
Tierling, Sascha4, Autor
Böhm, Julia W.4, Autor
Grote, Phillip3, Autor           
Lienhard, Matthias5, Autor           
Dietrich, Jörn1, Autor
Timmermann, Bernd6, Autor           
Walter, Jörn4, Autor
Schweiger, Michal R.7, Autor           
Lehrach, Hans2, Autor           
Herwig, Ralf5, Autor           
Herrmann, Bernhard G.3, Autor           
Morkel, Markus3, Autor           
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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 Zusammenfassung: 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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Sprache(n): eng - English
 Datum: 2013-02-07
 Publikationsstatus: Online veröffentlicht
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 Ort, Verlag, Ausgabe: -
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 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: PMC: 3567140
DOI: 10.1371/journal.pgen.1003250
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Titel: PLoS Genetics
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: San Francisco, USA : Public Library of Science
Seiten: - Band / Heft: 9 (2) Artikelnummer: - Start- / Endseite: e1003250 - e1003250 Identifikator: Anderer: PLoS Genet