A DNA methylation fingerprint of 1628 human samples
Open Access
- 25 May 2011
- journal article
- Published by Cold Spring Harbor Laboratory in Genome Research
- Vol. 22 (2), 407-419
- https://doi.org/10.1101/gr.119867.110
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.Keywords
This publication has 83 references indexed in Scilit:
- Prioritizing GWAS Results: A Review of Statistical Methods and Recommendations for Their ApplicationAmerican Journal of Human Genetics, 2010
- Human DNA methylomes at base resolution show widespread epigenomic differencesNature, 2009
- CpG islands – ‘A rough guide’FEBS Letters, 2009
- Highly Integrated Single-Base Resolution Maps of the Epigenome in ArabidopsisCell, 2008
- The Epigenomics of CancerCell, 2007
- A stem cell–like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencingNature Genetics, 2007
- DNA methylation profiling of human chromosomes 6, 20 and 22Nature Genetics, 2006
- Control of Developmental Regulators by Polycomb in Human Embryonic Stem CellsCell, 2006
- Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cellsNature Genetics, 2005
- Aberrant CpG-island methylation has non-random and tumour-type–specific patternsNature Genetics, 2000