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| Status |
Public on May 01, 2018 |
| Title |
Heterogeneous DNA methylation changes in acute myeloid leukemia associate with cancer-specific gene expression signatures and disruption of the hematopoietic regulatory network |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
DNA methylation is known as a stable epigenetic mark that is linked to gene silencing in cancer. Specific sets of DNA methylation changes have been linked to cancer subgroups. Here we generated genome-wide DNA methylation profiles of acute myeloid leukemia (AML) patient samples. A subset of genomic regions showed extensive hypervariation among AML patients. As such, none of the identified differentially methylated regions (DMRs) as compared to normal heamatopoietic precursor cells were common to all AML cases. Gain of methylation is restricted to regions that in human ES cells are marked with both H3K27me3 and H3K4me3 (bivalent marks). These regions are associated with lowly expressed and silent genes in healthy progenitors. Expression changes associated with aberrant methylation occurred infrequently, but revealed a small and highly specific subset of DMRs associated with myeloid function and cancer-specific pathways. Furthermore, loss of DNA methylation in AML specifically targeted a small number modules in heamatopoietic regulatory networks, in a mutually exclusive manner. Our data emphasize the variation in DNA methylation patterns between different AML cases, but shows that among these changes, a core set of changes drives cancer-essential alterations in gene expression and regulation.
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| Overall design |
To investigate DNA methylation in acute myeloid leukemia (AML) in a genome-wide unbiased fashion, we applied MethylCap-seq. This method involves capture of methylated DNA using the MBD domain of MeCP2, and subsequent next-generation Illumina sequencing of eluted DNA.
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| Contributor(s) |
Brinkman AB, Simmer F, Kaan A, Altucci L, Stunnenberg HG |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Nov 20, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Arjen Brinkman |
| E-mail(s) |
arjen.brinkman@gmail.com
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| Organization name |
Radboud University, Nijmegen Center for Molecular Life Sciences
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| Department |
Molecular Biology
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| Lab |
Stunnenberg
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| Street address |
NCMLS #274, Geert Grooteplein Zuid 30
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| City |
Nijmegen |
| ZIP/Postal code |
6525 GA |
| Country |
Netherlands |
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| Platforms (1) |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
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| Samples (20)
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| Relations |
| BioProject |
PRJNA229431 |
| SRA |
SRP033222 |
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