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Epigenetic deregulation in pediatric acute lymphoblastic leukemia.
- Source :
-
Epigenetics [Epigenetics] 2014 Mar; Vol. 9 (3), pp. 459-67. Date of Electronic Publication: 2014 Jan 06. - Publication Year :
- 2014
-
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.
Details
- Language :
- English
- ISSN :
- 1559-2308
- Volume :
- 9
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Epigenetics
- Publication Type :
- Academic Journal
- Accession number :
- 24394348
- Full Text :
- https://doi.org/10.4161/epi.27585