RT Journal
A1 Fernandez, Agustin F
A1 Assenov, Yassen
A1 Martin-Subero, Jose
A1 Balint, Balazs
A1 Siebert, Reiner
A1 Taniguchi, Hiroaki
A1 Yamamoto, Hiroyuki
A1 Hidalgo, Manuel
A1 Tan, Aik-Choon
A1 Galm, Oliver
A1 Ferrer, Isidre
A1 Sanchez-Cespedes, Montse
A1 Villanueva, Alberto
A1 Carmona, Javier
A1 Sanchez-Mut, Jose V
A1 Berdasco, Maria
A1 Moreno, Victor
A1 Capella, Gabriel
A1 Monk, David
A1 Ballestar, Esteban
A1 Ropero, Santiago
A1 Martinez, Ramon
A1 Sanchez-Carbayo, Marta
A1 Prosper, Felipe
A1 Agirre, Xabier
A1 Fraga, Mario F
A1 Graña, Osvaldo
A1 Perez-Jurado, Luis
A1 Mora, Jaume
A1 Puig, Susana
A1 Prat, Jaime
A1 Badimon, Lina
A1 Puca, Annibale A
A1 Meltzer, Stephen J
A1 Lengauer, Thomas
A1 Bridgewater, John
A1 Bock, Christoph
A1 Esteller, Manel
T1 A DNA methylation fingerprint of 1,628 human samples
JF Genome Research 
JO Genome Research 
YR 2011 
FD May 25 
DO 10.1101/gr.119867.110 
SP gr.119867.110 
UL http://genome.cshlp.org/content/early/2011/05/25/gr.119867.110.abstract 
AB 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.