DNA methylation is the best characterized of the different layers that make up the epigenetic setting. Most of the studies characterizing DNA methylation patterns have been restricted to particular genomic loci in a limited number of human samples and pathological conditions. The recently arrived single-base-resolution technologies for DNA methylation are extremely helpful tools, but are not yet applicable and affordable for studying large groups of subjects. Herein, we present a compromise between an extremely comprehensive study of a human sample population with an intermediate level of resolution of CpGs at the genomic level. We obtained a DNA methylation fingerprint of 1,628 human samples where we interrogated 1,505 CpG sites. The DNA methylation patterns revealed show this epigenetic mark to be critical in tissue-type definition and stemness, particularly around transcription start sites that are not within a CpG island. For disease, the generated DNA methylation fingerprints show that, during tumorigenesis, human cancer cells underwent a progressive gain of promoter CpG island hypermethylation and a loss of CpG methylation in non-CpG island promoters. Although transformed cells are those where DNA methylation disruption is more obvious, we observed that other common human diseases, such as neurological and autoimmune disorders, had their own distinct DNA methylation profiles. Most importantly, we provide proof of principle that the obtained DNA methylation fingerprints might be useful for translational purposes by showing that are able to identify the tumor type origin of Cancers of Unknown Primary (CUPs). Thus, the DNA methylation patterns identified across the largest spectrum of samples, tissues and diseases reported to date constitute a baseline for developing higher-resolution DNA methylation maps, and provide important clues concerning the contribution of CpG methylation to tissue identity and its changes in the most prevalent human diseases.
Source: A DNA methylation fingerprint of 1,628 human samples. Agustin F. Fernandez, Yassen Assenov, Jose Ignacio Martin-Subero, Balazs Balint, Reiner Siebert, Hiroaki Taniguchi, Hiroyuki Yamamoto, Manuel Hidalgo, Aik-Choon Tan, Oliver Galm, Isidre Ferrer, Montse Sanchez-Cespedes, Alberto Villanueva, Javier Carmona, Jose V. Sanchez-Mut, Maria Berdasco, Victor Moreno, Gabriel Capella, David Monk, Esteban Ballestar, Santiago Ropero, Ramon Martinez, Marta Sanchez-Carbayo, Felipe Prosper, Xabier Agirre, Mario F. Fraga, Osvaldo Graña, Luis Perez-Jurado, Jaume Mora, Susana Puig, Jaime Prat, Lina Badimon, Annibale A. Puca, Stephen J. Meltzer, Thomas Lengauer, John Bridgewater, Christoph Bock & Manel Esteller (mesteller@idibell.cat). Genome Res. 2011 May 25
La plupart des études caractérisant les profils de méthylation d'ADN ont été restreintes à des locus génomiques particuliers, dans un nombre d'échantillons humains et de conditions pathologiques limités. Des chercheurs ont obtenu une empreinte de méthylation d’ADN de 1.628 échantillons humains, où 1.505 sites CpG (cibles de méthylation) ont été examinés. Il apparaît de ceci que les profils de méthylation sont critiques dans la définition des types tissulaires et du caractère « souche », en particulier autour des sites de début de transcription qui ne sont pas dans un îlot CpG. Les profils de méthylation ont aussi montré que, au cours de la tumorigenèse, les cellules cancéreuses humaines subissent une hausse progressive de l'hyperméthylation des îlots « CpG » et une perte de méthylation de CpG dans les îlots « non-CpG » des promoteurs de gènes. Plus important encore, les chercheurs fournissent une « preuve de principe » que les empreintes de méthylation de l'ADN sont capables d'identifier l'origine des cancers de primitif inconnu (CAPI).
Article (en anglais) librement disponible à l’adresse : http://genome.cshlp.org/content/early/2011/05/25/gr.119867.110.long
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