Genomics

Dataset Information

49

A DNA Methylation Fingerprint of 1,628 Human Samples


ABSTRACT: 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. Overall design: It was studied the genomic DNA from 1,628 human samples corresponding to 424 normal tissues (180 leukocytes, 97 colon mucosa and 227 other normal samples), 1,054 tumorigenic samples (premalignant lesions, primary tumors and metastases) and 150 non-cancerous disorders, such as brain lesions from Alzheimer’s disease, dementia with Lewy bodies, aortic atherosclerotic lesions, myopathies and autoimmune disorders.

INSTRUMENT(S): Illumina GoldenGate Methylation Cancer Panel I

SUBMITTER: Agustin F Fernandez  

PROVIDER: GSE28094 | GEO | 2011-05-24

SECONDARY ACCESSION(S): PRJNA139783

REPOSITORIES: GEO

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Publications

A DNA methylation fingerprint of 1628 human samples.

Fernandez Agustin F AF   Assenov Yassen Y   Martin-Subero Jose Ignacio JI   Balint Balazs B   Siebert Reiner R   Taniguchi Hiroaki H   Yamamoto Hiroyuki H   Hidalgo Manuel M   Tan Aik-Choon AC   Galm Oliver O   Ferrer Isidre I   Sanchez-Cespedes Montse M   Villanueva Alberto A   Carmona Javier J   Sanchez-Mut Jose V JV   Berdasco Maria M   Moreno Victor V   Capella Gabriel G   Monk David D   Ballestar Esteban E   Ropero Santiago S   Martinez Ramon R   Sanchez-Carbayo Marta M   Prosper Felipe F   Agirre Xabier X   Fraga Mario F MF   Graña Osvaldo O   Perez-Jurado Luis L   Mora Jaume J   Puig Susana S   Prat Jaime J   Badimon Lina L   Puca Annibale A AA   Meltzer Stephen J SJ   Lengauer Thomas T   Bridgewater John J   Bock Christoph C   Esteller Manel M  

Genome research 20110525 2


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  ...[more]

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