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.
| Language | English |
|---|---|
| Pages | 407-419 |
| Number of pages | 13 |
| Journal | Genome Research |
| Volume | 22 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 1 Feb 2012 |
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
Cite this
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A DNA methylation fingerprint of 1628 human samples. / Fernandez, Agustin F.; Assenov, Yassen; Martin-Subero, Jose Ignacio; Balint, Balazs; Siebert, Reiner; Taniguchi, Hiroaki; Yamamoto, Hiroyuki; Hidalgo, Manuel; Tan, Aik Choon; Galm, Oliver; Ferrer, Isidre; Sanchez-Cespedes, Montse; Villanueva, Alberto; Carmona, Javier; Sanchez-Mut, Jose V.; Berdasco, Maria; Moreno, Victor; Capella, Gabriel; Monk, David; Ballestar, Esteban; Ropero, Santiago; Martinez, Ramon; Sanchez-Carbayo, Marta; Prosper, Felipe; Agirre, Xabier; Fraga, Mario F.; Graña, Osvaldo; Perez-Jurado, Luis; Mora, Jaume; Puig, Susana; Prat, Jaime; Badimon, Lina; Puca, Annibale A.; Meltzer, Stephen J.; Lengauer, Thomas; Bridgewater, John; Bock, Christoph; Esteller, Manel.
In: Genome Research, Vol. 22, No. 2, 01.02.2012, p. 407-419.Research output: Contribution to journal › Article
TY - JOUR
T1 - A DNA methylation fingerprint of 1628 human samples
AU - Fernandez, Agustin F.
AU - Assenov, Yassen
AU - Martin-Subero, Jose Ignacio
AU - Balint, Balazs
AU - Siebert, Reiner
AU - Taniguchi, Hiroaki
AU - Yamamoto, Hiroyuki
AU - Hidalgo, Manuel
AU - Tan, Aik Choon
AU - Galm, Oliver
AU - Ferrer, Isidre
AU - Sanchez-Cespedes, Montse
AU - Villanueva, Alberto
AU - Carmona, Javier
AU - Sanchez-Mut, Jose V.
AU - Berdasco, Maria
AU - Moreno, Victor
AU - Capella, Gabriel
AU - Monk, David
AU - Ballestar, Esteban
AU - Ropero, Santiago
AU - Martinez, Ramon
AU - Sanchez-Carbayo, Marta
AU - Prosper, Felipe
AU - Agirre, Xabier
AU - Fraga, Mario F.
AU - Graña, Osvaldo
AU - Perez-Jurado, Luis
AU - Mora, Jaume
AU - Puig, Susana
AU - Prat, Jaime
AU - Badimon, Lina
AU - Puca, Annibale A.
AU - Meltzer, Stephen J.
AU - Lengauer, Thomas
AU - Bridgewater, John
AU - Bock, Christoph
AU - Esteller, Manel
PY - 2012/2/1
Y1 - 2012/2/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84856555311&partnerID=8YFLogxK
U2 - 10.1101/gr.119867.110
DO - 10.1101/gr.119867.110
M3 - Article
VL - 22
SP - 407
EP - 419
JO - Genome Research
T2 - Genome Research
JF - Genome Research
SN - 1088-9051
IS - 2
ER -