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DNA methylome analysis of acute lymphoblastic leukemia cells reveals stochastic de novo DNA methylation in CpG islands
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
McGill Univ, Dept Human Genet, Montreal, PQ, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ, Canada..
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2016 (English)In: Epigenomics, ISSN 1750-1911, Vol. 8, no 10, 1367-1387 p.Article in journal (Refereed) Published
Abstract [en]

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.
Keyword [en]
acute lymphoblastic leukemia, CpG islands, DNA methylation, epigenome, methylome, whole-genome bisulfite sequencing
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:uu:diva-308929DOI: 10.2217/epi-2016-0052ISI: 000385653900006PubMedID: 27552300OAI: oai:DiVA.org:uu-308929DiVA: diva2:1051151
Funder
Swedish 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
Available from: 2016-12-01 Created: 2016-12-01 Last updated: 2016-12-01Bibliographically approved

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Wahlberg, PerLundmark, AndersNordlund, JessicaRaine, AmandaTandre, KarolinaRönnblom, LarsLönnerholm, GudmarSyvänen, Ann-Christine
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Molecular MedicineScience for Life Laboratory, SciLifeLabRheumatologyPediatrics
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