Hypermethylation and down-regulation of DLEU2 in paediatric acute myeloid leukaemia independent of embedded tumour suppressor miR-15a/16-1
| Autor: | Ngaire Elwood, Nicholas C. Wong, Minhee S. Halemba, Richard Saffery, Francoise Mechinaud, Mandy Parkinson-Bates, Jane L Ng, Leah Morenos, Zac Chatterton |
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| Jazyk: | angličtina |
| Předmět: |
Male
DLEU2 Cancer Research Myeloid Trisomy 8 Epigenesis Genetic 0302 clinical medicine AML Leukaemia Child Regulation of gene expression 0303 health sciences Gene Expression Regulation Leukemic Remission Induction MicroRNA Methylation 3. Good health Leukemia Leukemia Myeloid Acute medicine.anatomical_structure Oncology Paediatric 030220 oncology & carcinogenesis Child Preschool DNA methylation Molecular Medicine Female RNA Long Noncoding Chromosomes Human Pair 8 Signal Transduction Adolescent Antineoplastic Agents Biology 03 medical and health sciences Cytogenetics miR-15a/16-1 Transferases Cell Line Tumor microRNA medicine Humans Epigenetics 030304 developmental biology Chromosome Aberrations DNA ethylation Research Chromosomes Human Pair 11 Tumor Suppressor Proteins Infant DNA Methylation medicine.disease MicroRNAs Genetic Loci Immunology Cancer research Protein Processing Post-Translational |
| Zdroj: | Molecular Cancer |
| ISSN: | 1476-4598 |
| DOI: | 10.1186/1476-4598-13-123 |
| Popis: | Background Acute Myeloid Leukaemia (AML) is a highly heterogeneous disease. Studies in adult AML have identified epigenetic changes, specifically DNA methylation, associated with leukaemia subtype, age of onset and patient survival which highlights this heterogeneity. However, only limited DNA methylation studies have elucidated any associations in paediatric AML. Methods We interrogated DNA methylation on a cohort of paediatric AML FAB subtype M5 patients using the Illumina HumanMethylation450 (HM450) BeadChip, identifying a number of target genes with p 0.4 between leukaemic and matched remission (n = 20 primary leukaemic, n = 13 matched remission). Amongst those genes identified, we interrogate DLEU2 methylation using locus-specific SEQUENOM MassARRAY® EpiTYPER® and an increased validation cohort (n = 28 primary leukaemic, n = 14 matched remission, n = 17 additional non-leukaemic and cell lines). Following methylation analysis, expression studies were undertaken utilising the same patient samples for singleplex TaqMan gene and miRNA assays and relative expression comparisons. Results We identified differential DNA methylation at the DLEU2 locus, encompassing the tumour suppressor microRNA miR-15a/16-1 cluster. A number of HM450 probes spanning the DLEU2/Alt1 Transcriptional Start Site showed increased levels of methylation in leukaemia (average over all probes >60%) compared to disease-free haematopoietic cells and patient remission samples ( |
| Databáze: | OpenAIRE |
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