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dc.contributor.authorNordlund, Jessica
dc.contributor.authorBäcklin, Christopher L.
dc.contributor.authorWahlberg, Per
dc.contributor.authorBusche, Stephan
dc.contributor.authorBerglund, Eva C.
dc.contributor.authorEloranta, Maija-Leena
dc.contributor.authorFlægstad, Trond
dc.contributor.authorForestier, Erik
dc.contributor.authorFrost, Britt-Marie
dc.contributor.authorHarila-Saari, Arja
dc.contributor.authorHeyman, Mats
dc.contributor.authorJonsson, Olafur G.
dc.contributor.authorLarsson, Rolf
dc.contributor.authorPalle, Josefine
dc.contributor.authorRönnblom, Lars
dc.contributor.authorSchmiegelow, Kjeld
dc.contributor.authorSinnett, Daniel
dc.contributor.authorSöderhäll, Stefan
dc.contributor.authorPastinen, Tomi
dc.contributor.authorGustafsson, Mats G.
dc.contributor.authorLönnerholm, Gudmar
dc.contributor.authorSyvänen, Ann-Christine
dc.date.accessioned2022-06-29T06:58:32Z
dc.date.available2022-06-29T06:58:32Z
dc.date.issued2013-09-24
dc.description.abstractBackground: Although aberrant DNA methylation has been observed previously in acute lymphoblastic leukemia (ALL), the patterns of differential methylation have not been comprehensively determined in all subtypes of ALL on a genome-wide scale. The relationship between DNA methylation, cytogenetic background, drug resistance and relapse in ALL is poorly understood.<p> <p>Results: We surveyed the DNA methylation levels of 435,941 CpG sites in samples from 764 children at diagnosis of ALL and from 27 children at relapse. This survey uncovered four characteristic methylation signatures. First, compared with control blood cells, the methylomes of ALL cells shared 9,406 predominantly hypermethylated CpG sites, independent of cytogenetic background. Second, each cytogenetic subtype of ALL displayed a unique set of hyper- and hypomethylated CpG sites. The CpG sites that constituted these two signatures differed in their functional genomic enrichment to regions with marks of active or repressed chromatin. Third, we identified subtype-specific differential methylation in promoter and enhancer regions that were strongly correlated with gene expression. Fourth, a set of 6,612 CpG sites was predominantly hypermethylated in ALL cells at relapse, compared with matched samples at diagnosis. Analysis of relapse-free survival identified CpG sites with subtype-specific differential methylation that divided the patients into different risk groups, depending on their methylation status. <p>Conclusions: Our results suggest an important biological role for DNA methylation in the differences between ALL subtypes and in their clinical outcome after treatment.en_US
dc.identifier.citationNordlund, Bäcklin, Wahlberg, Busche, Berglund, Eloranta M, Flægstad T, Forestier E, Frost B, Harila-Saari A, Heyman M, Jonsson OG, Larsson R, Palle J, Rönnblom L, Schmiegelow K, Sinnett, Söderhäll S, Pastinen, Gustafsson, Lönnerholm G, Syvänen A. Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia. Genome Biology. 2013;14(9)en_US
dc.identifier.cristinIDFRIDAID 1115969
dc.identifier.doi10.1186/gb-2013-14-9-r105
dc.identifier.issn1465-6906
dc.identifier.issn1474-760X
dc.identifier.urihttps://hdl.handle.net/10037/25637
dc.language.isoengen_US
dc.publisherBMCen_US
dc.relation.journalGenome Biology
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2013 The Author(s)en_US
dc.titleGenome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemiaen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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