Journal
EPIGENOMICS
Volume 8, Issue 10, Pages 1367-1387Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/epi-2016-0052
Keywords
acute lymphoblastic leukemia; CpG islands; DNA methylation; epigenome; methylome; whole-genome bisulfite sequencing
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Funding
- Swedish Foundation for Strategic Research [RBc08-008]
- Swedish Cancer Society [140581]
- Swedish Childhood Cancer Foundation [PR2014-0100]
- Swedish Research Council for Science and Technology (VR-NT) [C0524801]
- Swedish Research Council FORTE
- Swedish Research Council FORMAS
- Swedish Research Council VINNOVA
- Swedish Research Council VR [259-2012-23]
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Aim: To identify regions of aberrant DNA methylation in acute lymphoblastic leukemia (ALL) cells of different subtypes on a genome-wide scale. Materials & methods: Whole-genome bisulfite sequencing (WGBS) was used to determine the DNA methylation levels in cells from four pediatric ALL patients of different subtypes. The findings were confirmed by 450k DNA methylation arrays in a large patient set. Results: Compared with mature B or T cells WGBS detected on average 82,000 differentially methylated regions per patient. Differentially methylated regions are enriched to CpG poor regions, active enhancers and transcriptional start sites. We also identified approximately 8000 CpG islands with variable intermediate DNA methylation that seems to occur as a result of stochastic de novo methylation. Conclusion: WGBS provides an unbiased view and novel insights into the DNA methylome of ALL cells.
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