Multiplex Enhanced Reduced Representation Bisulfite Sequencing (mERRBS) Analysis of dic(1;7)(q10;p10) in Myelodysplastic Syndromes (MDS) compared to control cohort and therapy-related Myeloid Neoplasms (t-MN)
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PROVIDER: PRJNA485750 | ENA |
REPOSITORIES: ENA
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Project description:Gene expression profiling was significantly different between der(1;7)(q10;p10) and -7/7q- patients by cluster analysis. There were total 1628 dysregulated genes in both der(1;7)(q10;p10) and -7/del(7q) cohorts.
2017-09-22 | GSE100340 | GEO
Project description:The unbalanced translocation t(1;7)(q10;p10), generating 1q trisomy and 7q monosomy, is due to centromere-centromere juxtaposition. This dicentric chromosome is a recurrent change in myelodysplastic syndromes (MDS), with half the cases arising after chemo/radio-therapy. To date, given the absence of genes within the centromeric regions, no specific molecular events have been identified in this cytogenetic subgroup. We first identified a comprehensive genetic and epigenetic landscape of MDS with dic(1;7)(q10;p10) and compared it to normal controls and other therapy-related Myeloid Neoplasms (t-MNs). RNA-seq showed a unique downregulated signature in dic(1;7) cases, affecting more than 80% of differentially expressed genes. As revealed by pathway and gene ontology analyses, downregulation of ATP-binding cassette (ABC) transporters and of genes related to lipid metabolism, and upregulation of p53 signaling were the most relevant biological features of dicentric-positive MDS. Despite 1q trisomy, more than 50% of 1q deregulated genes were downregulated. This partial gene dosage effect was clarified by epigenetic analysis, which highlighted the presence of a specific hypermethylated pattern on 1q. Furthermore, in a supervised analysis, hypermethylation in all dicentrics clustered at intronic enhancers and was enriched for Krüppel-like transcription factors binding sites. Low expression levels of enhancer putative target genes accounted for more than 30% of the downregulated signature. Our findings demonstrate that alteration of centromeric DNA in dic(1;7) cases imposes a specific transcriptional program, driven by a unique epigenomic signature.
2019-09-01 | GSE118475 | GEO
Project description:The unbalanced translocation t(1;7)(q10;p10), generating 1q trisomy and 7q monosomy, is due to centromere-centromere juxtaposition. This dicentric chromosome is a recurrent change in myelodysplastic syndromes (MDS), with half the cases arising after chemo/radio-therapy. To date, given the absence of genes within the centromeric regions, no specific molecular events have been identified in this cytogenetic subgroup. We first identified a comprehensive genetic and epigenetic landscape of MDS with dic(1;7)(q10;p10) and compared it to normal controls and other therapy-related Myeloid Neoplasms (t-MNs). RNA-seq showed a unique downregulated signature in dic(1;7) cases, affecting more than 80% of differentially expressed genes. As revealed by pathway and gene ontology analyses, downregulation of ATP-binding cassette (ABC) transporters and of genes related to lipid metabolism, and upregulation of p53 signaling were the most relevant biological features of dicentric-positive MDS. Despite 1q trisomy, more than 50% of 1q deregulated genes were downregulated. This partial gene dosage effect was clarified by epigenetic analysis, which highlighted the presence of a specific hypermethylated pattern on 1q. Furthermore, in a supervised analysis, hypermethylation in all dicentrics clustered at intronic enhancers and was enriched for Krüppel-like transcription factors binding sites. Low expression levels of enhancer putative target genes accounted for more than 30% of the downregulated signature. Our findings demonstrate that alteration of centromeric DNA in dic(1;7) cases imposes a specific transcriptional program, driven by a unique epigenomic signature.
2019-09-01 | GSE118477 | GEO
Project description:The unbalanced translocation t(1;7)(q10;p10), generating 1q trisomy and 7q monosomy, is due to centromere-centromere juxtaposition. This dicentric chromosome is a recurrent change in myelodysplastic syndromes (MDS), with half the cases arising after chemo/radio-therapy. To date, given the absence of genes within the centromeric regions, no specific molecular events have been identified in this cytogenetic subgroup. We first identified a comprehensive genetic and epigenetic landscape of MDS with dic(1;7)(q10;p10) and compared it to normal controls and other therapy-related Myeloid Neoplasms (t-MNs). RNA-seq showed a unique downregulated signature in dic(1;7) cases, affecting more than 80% of differentially expressed genes. As revealed by pathway and gene ontology analyses, downregulation of ATP-binding cassette (ABC) transporters and of genes related to lipid metabolism, and upregulation of p53 signaling were the most relevant biological features of dicentric-positive MDS. Despite 1q trisomy, more than 50% of 1q deregulated genes were downregulated. This partial gene dosage effect was clarified by epigenetic analysis, which highlighted the presence of a specific hypermethylated pattern on 1q. Furthermore, in a supervised analysis, hypermethylation in all dicentrics clustered at intronic enhancers and was enriched for Krüppel-like transcription factors binding sites. Low expression levels of enhancer putative target genes accounted for more than 30% of the downregulated signature. Our findings demonstrate that alteration of centromeric DNA in dic(1;7) cases imposes a specific transcriptional program, driven by a unique epigenomic signature.
2019-09-01 | GSE118476 | GEO
Project description:Affymetrix SNP array data for dic(1;7)(q10;p10) in Myelodysplastic Syndromes (MDS)
| PRJNA485752 | ENA
Project description:Expression Analysis of dic(1;7)(q10;p10) in Myelodysplastic Syndromes (MDS) compared to control cohort and therapy-related Myeloid Neoplasms (t-MN)
| PRJNA485753 | ENA
Project description:Expression data from MDS patients with der(1;7)(q10;p10)
| PRJNA391405 | ENA
Project description:Our present study reveals significant decelerating effects on senescence processes in middle-aged SAMP1 mice supplemented for 6 or 14 months with the reduced form (QH2, 500 mg/ kg BW/ day) of coenzyme Q10 (CoQ10). To unravel molecular mechanisms of these CoQ10 effects, a genome-wide transcript profiling in liver, heart, brain and kidney of SAMP1 mice supplemented with the reduced (QH2) or oxidized form of CoQ10 (Q10) was performed. Liver seems to be the main target tissue of CoQ10 intervention, followed by kidney, heart and brain. Stringent evaluation of the resulting data revealed that QH2 has a stronger impact on gene expression than Q10, which was primarily due to differences in the bioavailability. Indeed, we found that QH2 supplementation was more effective than Q10 to increase levels of CoQ10 in the liver of SAMP1 mice (54.92-fold and 30.36-fold, respectively). To identify functional and regulatory connections of the âtop 50â (p < 0.05) up- and down-regulated QH2-sensitive transcripts in liver (fold changes ranging from 21.24 to -6.12), text mining analysis (Genomatix BiblioSphere, GFG level B3) was used. Hereby, we identified 11 QH2-sensitive genes which are regulated by PPAR-α and are primarily involved in cholesterol synthesis (e.g. HMGCS1, HMGCL, HMGCR), fat assimilation (FABP5), lipoprotein metabolism (PLTP) and inflammation (STAT-1). Thus, we provide evidence that QH2 is involved in the reduction of fat and cholesterol synthesis via modulation of the PPAR-α signalling pathway. These data may explain, at least in part, the observed effects on decelerated age-dependent degeneration processes in QH2-supplemented SAMP1 mice. Whole genome expression profiles were analysed from liver, heart, brain and kidney (each analyzed separately) of SAMP1 mice supplemented with QH2, Q10 or a control diet. From every experimental group, three mice each were sacrificed 6 or 14 months after supplementation, resulting in a total of 72 microarrays.
2010-03-15 | E-GEOD-15129 | biostudies-arrayexpress
Project description:In this study, to obtain a complete registry of genetic lesions in MDS and to identify novel therapeutic targets, we performed SNP array analysis and whole exome analysis for novel mutations using high-throughput sequencing technologies. In whole exome analysis, paired CD3-positive T cells were used as a normal control. By comparing sequences in tumors and paired T cells, 268 non-synonymous somatic mutations were confirmed with an overall true positive rate of 53.9 %, including 206 missense, 25 nonsense, and 10 splice site mutations, and 27 frameshift-causing insertions/deletions (indels). The mutations of the known gene targets, however, accounted for only 12.3 % of all detected mutations (N = 33), and the remaining 235 mutations involved previously unreported genes. Combined with the genomic copy number profile obtained by SNP array karyotyping, this array of somatic mutations provided a landscape of myelodysplasia genomes. Copy number analysis of Affymetrix 250K SNP arrays was performed for 29 MDS or related neoplasms and paired 29 germline samples.
2011-09-11 | E-GEOD-31174 | biostudies-arrayexpress