title: A DNA methylation fingerprint of 1628 human samples.
abstract: 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. 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 1628 human samples in which we interrogated 1505 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 in which 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 DNA methylation fingerprints obtained might be useful for translational purposes by showing that we are able to identify the tumor type origin of cancers of unknown primary origin (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.
authors: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, 08908 Barcelona, Catalonia, Spain.
authors: Agustin F
authors: AF
authors: Fernandez
authors: Yassen
authors: Y
authors: Assenov
authors: Jose Ignacio
authors: JI
authors: Martin-Subero
authors: Balazs
authors: B
authors: Balint
authors: Reiner
authors: R
authors: Siebert
authors: Hiroaki
authors: H
authors: Taniguchi
authors: Hiroyuki
authors: H
authors: Yamamoto
authors: Manuel
authors: M
authors: Hidalgo
authors: Aik-Choon
authors: AC
authors: Tan
authors: Oliver
authors: O
authors: Galm
authors: Isidre
authors: I
authors: Ferrer
authors: Montse
authors: M
authors: Sanchez-Cespedes
authors: Alberto
authors: A
authors: Villanueva
authors: Javier
authors: J
authors: Carmona
authors: Jose V
authors: JV
authors: Sanchez-Mut
authors: Maria
authors: M
authors: Berdasco
authors: Victor
authors: V
authors: Moreno
authors: Gabriel
authors: G
authors: Capella
authors: David
authors: D
authors: Monk
authors: Esteban
authors: E
authors: Ballestar
authors: Santiago
authors: S
authors: Ropero
authors: Ramon
authors: R
authors: Martinez
authors: Marta
authors: M
authors: Sanchez-Carbayo
authors: Felipe
authors: F
authors: Prosper
authors: Xabier
authors: X
authors: Agirre
authors: Mario F
authors: MF
authors: Fraga
authors: Osvaldo
authors: O
authors: Graña
authors: Luis
authors: L
authors: Perez-Jurado
authors: Jaume
authors: J
authors: Mora
authors: Susana
authors: S
authors: Puig
authors: Jaime
authors: J
authors: Prat
authors: Lina
authors: L
authors: Badimon
authors: Annibale A
authors: AA
authors: Puca
authors: Stephen J
authors: SJ
authors: Meltzer
authors: Thomas
authors: T
authors: Lengauer
authors: John
authors: J
authors: Bridgewater
authors: Christoph
authors: C
authors: Bock
authors: Manel
authors: M
authors: Esteller
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