1. Epigenetic deregulation in pediatric acute lymphoblastic leukemia.
- Author
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Chatterton Z, Morenos L, Mechinaud F, Ashley DM, Craig JM, Sexton-Oates A, Halemba MS, Parkinson-Bates M, Ng J, Morrison D, Carroll WL, Saffery R, and Wong NC
- Subjects
- Case-Control Studies, Child, CpG Islands, DNA Methylation, Female, Humans, Male, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma metabolism, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma pathology, Epigenesis, Genetic, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics
- 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.
- Published
- 2014
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