Epigenetic deregulation in pediatric acute lymphoblastic leukemia
Data(s) |
01/03/2014
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Resumo |
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. |
Identificador | |
Idioma(s) |
eng |
Publicador |
Taylor & Francis |
Relação |
http://dro.deakin.edu.au/eserv/DU:30070089/chatterton-epigenticderegulation-2014.pdf http://www.dx.doi.org/10.4161/epi.27585 http://www.ncbi.nlm.nih.gov/pubmed/24394348 |
Direitos |
2014, Taylor & Francis |
Palavras-Chave | #ALL #B-cell #DNA methylation #acute lymphoblastic leukemia #epigenetics #hematology #leukemia #Science & Technology #Life Sciences & Biomedicine #Biochemistry & Molecular Biology #Genetics & Heredity #ISLAND METHYLATOR PHENOTYPE #CHRONIC MYELOID-LEUKEMIA #CPG ISLAND #COLORECTAL-CANCER #L-ASPARAGINASE #PROMOTER HYPERMETHYLATION #TUMOR-SUPPRESSOR #DOWN-REGULATION #CELL-DEATH #Case-Control Studies #Child #Epigenesis, Genetic #Female #Humans #Male #Precursor B-Cell Lymphoblastic Leukemia-Lymphoma |
Tipo |
Journal Article |