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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
21
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pubmed:dateCreated |
2009-10-7
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pubmed:abstractText |
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, with high hyperdiploidy [51-67 chromosomes] and the t(12;21)(p13;q22) [ETV6/RUNX1 fusion] representing the most frequent abnormalities. Although these arise in utero, there is long latency before overt ALL, showing that additional changes are needed. Gene dysregulation through hypermethylation may be such an event; however, this has not previously been investigated in a detailed fashion. We performed genome-wide methylation profiling using bacterial artificial chromosome arrays and promoter-specific analyses of high hyperdiploid and ETV6/RUNX1-positive ALLs. In addition, global gene expression analyses were performed to identify associated expression patterns. Unsupervised cluster and principal component analyses of the chromosome-wide methylome profiles could successfully subgroup the two genetic ALL types. Analysis of all currently known promoter-specific CpG islands demonstrated that several B-cell- and neoplasia-associated genes were hypermethylated and underexpressed, indicating that aberrant methylation plays a significant leukemogenic role. Interestingly, methylation hotspots were associated with chromosome bands predicted to harbor imprinted genes and the tri-/tetrasomic chromosomes in the high hyperdiploid ALLs were less methylated than their disomic counterparts. Decreased methylation of gained chromosomes is a previously unknown phenomenon that may have ramifications not only for the pathogenesis of high hyperdiploid ALL but also for other disorders with acquired or constitutional numerical chromosome anomalies.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/BAD protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/BBC3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CAV1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CDK2AP1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caveolin 1,
http://linkedlifedata.com/resource/pubmed/chemical/Core Binding Factor Alpha 2 Subunit,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins, Fusion,
http://linkedlifedata.com/resource/pubmed/chemical/PRKCDBP protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TEL-AML1 fusion protein,
http://linkedlifedata.com/resource/pubmed/chemical/THEM4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-Associated Death Protein,
http://linkedlifedata.com/resource/pubmed/chemical/nucleophosmin
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1460-2083
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4054-65
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pubmed:meshHeading |
pubmed-meshheading:19679565-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:19679565-Apoptosis Regulatory Proteins,
pubmed-meshheading:19679565-Caveolin 1,
pubmed-meshheading:19679565-Child,
pubmed-meshheading:19679565-Chromosome Mapping,
pubmed-meshheading:19679565-Core Binding Factor Alpha 2 Subunit,
pubmed-meshheading:19679565-CpG Islands,
pubmed-meshheading:19679565-DNA Methylation,
pubmed-meshheading:19679565-Gene Expression Profiling,
pubmed-meshheading:19679565-Genome, Human,
pubmed-meshheading:19679565-Genome-Wide Association Study,
pubmed-meshheading:19679565-Humans,
pubmed-meshheading:19679565-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:19679565-Membrane Proteins,
pubmed-meshheading:19679565-Nuclear Proteins,
pubmed-meshheading:19679565-Oncogene Proteins, Fusion,
pubmed-meshheading:19679565-Precursor Cell Lymphoblastic Leukemia-Lymphoma,
pubmed-meshheading:19679565-Proto-Oncogene Proteins,
pubmed-meshheading:19679565-Sequence Analysis, DNA,
pubmed-meshheading:19679565-Tumor Suppressor Proteins,
pubmed-meshheading:19679565-bcl-Associated Death Protein
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pubmed:year |
2009
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pubmed:articleTitle |
The DNA methylome of pediatric acute lymphoblastic leukemia.
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pubmed:affiliation |
Department of Clinical Genetics, Lund University Hospital, Lund University, SE-221 85 Lund, Sweden. josef.davidsson@med.lu.se
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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