title: A comprehensive DNA methylation profile of epithelial-to-mesenchymal transition.
abstract: Epithelial-to-mesenchymal transition (EMT) is a plastic process in which fully differentiated epithelial cells are converted into poorly differentiated, migratory and invasive mesenchymal cells, and it has been related to the metastasis potential of tumors. This is a reversible process and cells can also eventually undergo mesenchymal-to-epithelial transition. The existence of a dynamic EMT process suggests the involvement of epigenetic shifts in the phenotype. Herein, we obtained the DNA methylomes at single-base resolution of Madin-Darby canine kidney cells undergoing EMT and translated the identified differentially methylated regions to human breast cancer cells undergoing a gain of migratory and invasive capabilities associated with the EMT phenotype. We noticed dynamic and reversible changes of DNA methylation, both on promoter sequences and gene-bodies in association with transcription regulation of EMT-related genes. Most importantly, the identified DNA methylation markers of EMT were present in primary mammary tumors in association with the epithelial or the mesenchymal phenotype of the studied breast cancer samples.
authors.affiliation: Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat; Barcelona, Spain.
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Carmona
authors.affiliation: Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat; Barcelona, Spain.
authors.forename: Veronica
authors.initials: V
authors.lastname: Davalos
authors.affiliation: Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat; Barcelona, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Vidal
authors.affiliation: Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat; Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gomez
authors.affiliation: Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat; Barcelona, Spain.
authors.forename: Holger
authors.initials: H
authors.lastname: Heyn
authors.affiliation: Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat; Barcelona, Spain.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat; Barcelona, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Vizoso
authors.affiliation: Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat; Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Martinez-Cardus
authors.affiliation: Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat; Barcelona, Spain.
authors.forename: Sergi
authors.initials: S
authors.lastname: Sayols
authors.affiliation: Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat; Barcelona, Spain.
authors.forename: Humberto J
authors.initials: HJ
authors.lastname: Ferreira
authors.affiliation: Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat; Barcelona, Spain.
authors.forename: Jose V
authors.initials: JV
authors.lastname: Sánchez-Mut
authors.affiliation: Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat; Barcelona, Spain.
authors.forename: Sebastián
authors.initials: S
authors.lastname: Morán
authors.affiliation: Catalan Institut of Oncology-Badalona, Badalona, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Margelí
authors.affiliation: Pathology Department, Hospital Germans Trias i Pujol, Badalona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Castella
authors.affiliation: Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat; Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Berdasco
authors.affiliation: Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat; Barcelona, Spain.
authors.forename: Olafur A
authors.initials: OA
authors.lastname: Stefansson
authors.affiliation: Cancer Research Laboratory, Faculty of Medicine, University of Iceland, Reykjavik, Iceland. Department of Medicine, University of Iceland, Reykjavik, Iceland.
authors.forename: Jorunn E
authors.initials: JE
authors.lastname: Eyfjord
authors.affiliation: Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat; Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Gonzalez-Suarez
authors.affiliation: Department of Bioinformatics, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain. CIBER de Enfermedades Raras (CIBERER), Valencia, Spain. Functional Genomics Node (INB) at CIPF, Valencia, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Dopazo
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain. Joint IRB-BSC Research Program on Computational Biology, Barcelona, Spain. Barcelona Supercomputing Center, Barcelona, Spain. Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain.
authors.forename: Modesto
authors.initials: M
authors.lastname: Orozco
authors.affiliation: Centre Nacional d'Anàlisi Genòmica (CNAG), Barcelona, Spain.
authors.forename: Ivo G
authors.initials: IG
authors.lastname: Gut
authors.affiliation: Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat; Barcelona, Spain. Department of Physiological Sciences II, School of Medicine, University of Barcelona, Barcelona, Spain. Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. mesteller@idibell.cat.
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation; D004285:Dogs; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D061985:Madin Darby Canine Kidney Cells