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Author  |
Chatterton, Z.; Morenos, L.; Mechinaud, F.; Ashley, D.M.; Craig, J.M.; Sexton-Oates, A.; Halemba, M.S.; Parkinson-Bates, M.; Ng, J.; Morrison, D.; Carroll, W.L.; Saffery, R.; Wong, N.C. |
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Title |
Epigenetic deregulation in pediatric acute lymphoblastic leukemia |
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Journal Article |
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Year |
2014 |
Publication |
Epigenetics : Official Journal of the DNA Methylation Society |
Abbreviated Journal |
Epigenetics |
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Volume |
9 |
Issue |
3 |
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Keywords |
All; B-cell; DNA methylation; acute lymphoblastic leukemia; epigenetics; hematology; leukemia |
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Abstract |
Similar to most cancers, genome-wide DNA methylation profiles are commonly altered in pediatric acute lymphoblastic leukemia (ALL); however, recent observations highlight that a large portion of malignancy-associated DNA methylation alterations are not accompanied by related gene expression changes. By analyzing and integrating the methylome and transcriptome profiles of pediatric B-cell ALL cases and primary tissue controls, we report 325 genes hypermethylated and downregulated and 45 genes hypomethylated and upregulated in pediatric B-cell ALL, irrespective of subtype. Repressed cation channel subunits and cAMP signaling activators and transducers are overrepresented, potentially indicating a reduced cellular potential to receive and propagate apoptotic signals. Furthermore, we report specific DNA methylation alterations with concurrent gene expression changes within individual ALL subtypes. The ETV6-RUNX1 translocation was associated with downregulation of ASNS and upregulation of the EPO-receptor, while Hyperdiploid patients (> 50 chr) displayed upregulation of B-cell lymphoma (BCL) members and repression of PTPRG and FHIT. In combination, these data indicate genetically distinct B-cell ALL subtypes contain cooperative epimutations and genome-wide epigenetic deregulation is common across all B-cell ALL subtypes. |
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Address |
Murdoch Childrens Research Institute; The University of Melbourne Department of Paediatrics at the Royal Children's Hospital; Victoria, VIC Australia |
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Language |
English |
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ISSN |
1559-2294 |
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Notes |
PMID:24394348 |
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Call Number |
CBM.UAM @ ccobaleda @ |
Serial |
459 |
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