DNA methylome analysis of acute lymphoblastic leukemia cells reveals stochastic de novo DNA methylation in CpG islands
2016 (English)In: Epigenomics, ISSN 1750-1911, Vol. 8, no 10, 1367-1387 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2016. Vol. 8, no 10, 1367-1387 p.
acute lymphoblastic leukemia, CpG islands, DNA methylation, epigenome, methylome, whole-genome bisulfite sequencing
IdentifiersURN: urn:nbn:se:uu:diva-308929DOI: 10.2217/epi-2016-0052ISI: 000385653900006PubMedID: 27552300OAI: oai:DiVA.org:uu-308929DiVA: diva2:1051151
FunderSwedish Foundation for Strategic Research , RBc08-008Swedish Cancer Society, 140581Swedish Childhood Cancer Foundation, PR2014-0100Swedish Research Council, C0524801;259-2012-23Forte, Swedish Research Council for Health, Working Life and WelfareSwedish Research Council FormasVINNOVA