title: DNA-methylome analysis of mouse intestinal adenoma identifies a tumour-specific signature that is partly conserved in human colon cancer.
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 APC(Min) 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.
authors: Max Planck Institute for Molecular Genetics, Department of Vertebrate Genomics, Berlin, Germany.
authors: Christina
authors: C
authors: Grimm
authors: Lukas
authors: L
authors: Chavez
authors: Mireia
authors: M
authors: Vilardell
authors: Alexandra L
authors: AL
authors: Farrall
authors: Sascha
authors: S
authors: Tierling
authors: Julia W
authors: JW
authors: Böhm
authors: Phillip
authors: P
authors: Grote
authors: Matthias
authors: M
authors: Lienhard
authors: Jörn
authors: J
authors: Dietrich
authors: Bernd
authors: B
authors: Timmermann
authors: Jörn
authors: J
authors: Walter
authors: Michal R
authors: MR
authors: Schweiger
authors: Hans
authors: H
authors: Lehrach
authors: Ralf
authors: R
authors: Herwig
authors: Bernhard G
authors: BG
authors: Herrmann
authors: Markus
authors: M
authors: Morkel
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D001483:Base Sequence; D003110:Colonic Neoplasms / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D057890:Epigenomics; D016678:Genome; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D063146:Polycomb-Group Proteins / Q000235:genetics*; D026801:Synteny
chemical_list: D063146:Polycomb-Group Proteins