Distinct Epigenetic Subtypes Are Linked to Disease Progression in Low-Risk MDS
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ABSTRACT:
PROVIDER: PRJNA422911 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6387510.fastq.gz | Fastqsanger.gz | |||
| SRR6387520.fastq.gz | Fastqsanger.gz | |||
| SRR6387530.fastq.gz | Fastqsanger.gz | |||
| SRR6387540.fastq.gz | Fastqsanger.gz | |||
| SRR6387511.fastq.gz | Fastqsanger.gz |
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Project description:Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders characterized variably by the presence of peripheral cytopenias, bone marrow hypercellularity and dysplastic changes in the bone marrow. While MDS patients have an increased risk of progression to acute myeloid leukemia (AML), most MDS patients actually succumb to progressive bone marrow failure. Amongst patients classified as low-risk MDS, different clinical evolutions have been observed, with some patients remaining relatively stable for long periods of time (herein, stable MDS), while others show more progressive disease, with worsening cytopenias, and often increased transfusion requirements (herein, progressive MDS). Current risk stratification strategies fail to distinguish these two groups at diagnosis. We report here that these distinct behaviors are encoded at the epigenetic level and that examining DNA methylation profiles of low-risk MDS patients captures underlying differences between the two different groups. In this study, we identified 356 differentially methylated regions (DMRs) between stable and progressive low-risk MDS at the time of diagnosis. The number of DMRs was almost doubled at the time of progression (681 follow-up DMRs), and this was accompanied by an increase in the local variability at specific methylation regions, and an increase in heterogeneity over time. These findings reveal previously unrecognized epigenetic heterogeneity in low-risk MDS patients and opens the possibility for using epigenetic differences to help improve risk-stratification at diagnosis.
2020-04-14 | GSE108247 | GEO
Project description: Not available
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Project description:Genome-wide expression and methylation profiling identifies novel targets with aberrant hypermethylation and reduced expression in low-risk myelodysplastic syndromes (MDSs). Gene expression profiling signatures may be used to classify the subtypes of Myelodysplastic syndrome (MDS) patients. However, there are few reports on the global methylation status in MDS. The integration of genome-wide epigenetic regulatory marks with gene expression levels would provide additional information regarding the biological differences between MDS and healthy controls. Gene expression and methylation status were measured using high-density microarrays. A total of 552 differentially methylated CpG loci were identified as being present in low-risk MDS; hypermethylated genes were more frequent than hypomethylated genes. In addition, mRNA expression profiling identified 1005 genes that significantly differed between low-risk MDS and the control group. Integrative analysis of the epigenetic and expression profiles revealed that 66.7% of the hypermethylated genes were underexpressed in low-risk MDS cases. Gene network analysis revealed molecular mechanisms associated with the low-risk MDS group, including altered apoptosis pathways. The two key apoptotic genes BCL2 and ETS1 were identified as silenced genes. In addition, the immune response and micro RNA biogenesis were affected by the hypermethylation and underexpression of IL27RA and DICER1. Our integrative analysis revealed that aberrant epigenetic regulation is a hallmark of low-risk MDS patients and could have a central role in these diseases. Low-risk MDS patients and age-matched controls without haematological malignancies were included in the study. Mononuclear cells were isolated from bone marrow samples of low-risk MDS patients and controls by density gradient (Ficoll). A cohort of 18 patients with low-risk MDS and seven controls were included in a simultaneous integrative study of methylation and expression, while the whole series was used as a control group of expression data.
2012-09-25 | E-GEOD-41130 | biostudies-arrayexpress
Project description:Genome-wide expression and methylation profiling identifies novel targets with aberrant hypermethylation and reduced expression in low-risk myelodysplastic syndromes (MDSs). Gene expression profiling signatures may be used to classify the subtypes of Myelodysplastic syndrome (MDS) patients. However, there are few reports on the global methylation status in MDS. The integration of genome-wide epigenetic regulatory marks with gene expression levels would provide additional information regarding the biological differences between MDS and healthy controls. Gene expression and methylation status were measured using high-density microarrays. A total of 552 differentially methylated CpG loci were identified as being present in low-risk MDS; hypermethylated genes were more frequent than hypomethylated genes. In addition, mRNA expression profiling identified 1005 genes that significantly differed between low-risk MDS and the control group. Integrative analysis of the epigenetic and expression profiles revealed that 66.7% of the hypermethylated genes were underexpressed in low-risk MDS cases. Gene network analysis revealed molecular mechanisms associated with the low-risk MDS group, including altered apoptosis pathways. The two key apoptotic genes BCL2 and ETS1 were identified as silenced genes. In addition, the immune response and micro RNA biogenesis were affected by the hypermethylation and underexpression of IL27RA and DICER1. Our integrative analysis revealed that aberrant epigenetic regulation is a hallmark of low-risk MDS patients and could have a central role in these diseases. Low-risk MDS patients and age-matched controls without haematological malignancies were included in the study. Mononuclear cells were isolated from bone marrow samples of low-risk MDS patients and controls by density gradient (Ficoll). A cohort of 18 patients with low-risk MDS and seven controls were included in a simultaneous integrative study of methylation (using Methylated CpG Island Amplification and Microarrays, MCAM) and expression (using Affymetrix microarrays HG-U133 Plus 2), while the whole series was used as a control group of expression data.
2012-09-28 | E-GEOD-41215 | biostudies-arrayexpress
Project description:CD34+ transriptome analysis of lower-risk MDS at risk of rapid progression
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Project description:A role for reduced ribosomal protein gene dosage in both DBA and 5q- MDS suggests that other forms of MDS might also involve altered expression of ribosomal protein genes. We used microarrays to interrogate the expression of ribosomal proteins from purified hematopoietic stems cells from patients with low risk myelodysplastic syndrome and age-matched healthy controls. Hematopoietic stem cells were sorted from 8 patients with low risk myelodysplastic syndrome and 11 age-matched healthy controls, and total RNA was hybridized to Affymetrix microarrays.
2011-08-13 | E-GEOD-30201 | biostudies-arrayexpress
Project description:Genome-wide expression and methylation profiling identifies novel targets with aberrant hypermethylation and reduced expression in low-risk myelodysplastic syndromes (MDSs). Gene expression profiling signatures may be used to classify the subtypes of Myelodysplastic syndrome (MDS) patients. However, there are few reports on the global methylation status in MDS. The integration of genome-wide epigenetic regulatory marks with gene expression levels would provide additional information regarding the biological differences between MDS and healthy controls. Gene expression and methylation status were measured using high-density microarrays. A total of 552 differentially methylated CpG loci were identified as being present in low-risk MDS; hypermethylated genes were more frequent than hypomethylated genes. In addition, mRNA expression profiling identified 1005 genes that significantly differed between low-risk MDS and the control group. Integrative analysis of the epigenetic and expression profiles revealed that 66.7% of the hypermethylated genes were underexpressed in low-risk MDS cases. Gene network analysis revealed molecular mechanisms associated with the low-risk MDS group, including altered apoptosis pathways. The two key apoptotic genes BCL2 and ETS1 were identified as silenced genes. In addition, the immune response and micro RNA biogenesis were affected by the hypermethylation and underexpression of IL27RA and DICER1. Our integrative analysis revealed that aberrant epigenetic regulation is a hallmark of low-risk MDS patients and could have a central role in these diseases.
2012-09-28 | GSE41215 | GEO
Project description:Genome-wide expression and methylation profiling identifies novel targets with aberrant hypermethylation and reduced expression in low-risk myelodysplastic syndromes (MDSs). Gene expression profiling signatures may be used to classify the subtypes of Myelodysplastic syndrome (MDS) patients. However, there are few reports on the global methylation status in MDS. The integration of genome-wide epigenetic regulatory marks with gene expression levels would provide additional information regarding the biological differences between MDS and healthy controls. Gene expression and methylation status were measured using high-density microarrays. A total of 552 differentially methylated CpG loci were identified as being present in low-risk MDS; hypermethylated genes were more frequent than hypomethylated genes. In addition, mRNA expression profiling identified 1005 genes that significantly differed between low-risk MDS and the control group. Integrative analysis of the epigenetic and expression profiles revealed that 66.7% of the hypermethylated genes were underexpressed in low-risk MDS cases. Gene network analysis revealed molecular mechanisms associated with the low-risk MDS group, including altered apoptosis pathways. The two key apoptotic genes BCL2 and ETS1 were identified as silenced genes. In addition, the immune response and micro RNA biogenesis were affected by the hypermethylation and underexpression of IL27RA and DICER1. Our integrative analysis revealed that aberrant epigenetic regulation is a hallmark of low-risk MDS patients and could have a central role in these diseases.
2012-09-25 | GSE41130 | GEO
Project description:The diagnosis of myelodysplastic syndromes (MDS) remains problematic due to the subjective nature of morphological assessment. The reported high frequency of somatic mutations and increased structural variants by array-based cytogenetics have provided potential objective markers of disease however this has been complicated by reports of similar abnormalities in the healthy population. We aimed to identify distinguishing features between those with early MDS and reported healthy individuals by characterising 69 patients who, following a non-diagnostic marrow, developed progressive dysplasia or acute myeloid leukaemia (AML). Targeted sequencing and array based cytogenetics identified a driver mutation and/or structural variant in 91% (63/69) of pre-diagnostic samples with the mutational spectrum mirroring that in the MDS population. When compared with the reported healthy population the mutations detected had significantly greater median variant allele fraction (40% vs 9-10%) and occurred more commonly with additional mutations (≥2 mutations 64% vs. 8%). Furthermore mutational analysis identified a high-risk group of patients with shorter time to disease progression and poorer overall survival. The mutational features in our cohort are distinct from those seen in the healthy population and, even in the absence of definitive disease, can predict outcome. Early detection may allow consideration of intervention in poor risk patients. We performed array based cytogenetics using HumanCytoSNP-12 (Illumina) on 69 patients diagnosed with acute myeloid leukaemia or myelodysplastic syndrome who had a previously non-diagnostic sample. SNP array analysis was performed on all diagnostic samples. In those with a documented abnormality, SNP-A was performed on the corresponding pre-diagnostic sample (n=32).
2015-09-17 | E-GEOD-73074 | biostudies-arrayexpress
Project description:A role for reduced ribosomal protein gene dosage in both DBA and 5q- MDS suggests that other forms of MDS might also involve altered expression of ribosomal protein genes. We used microarrays to interrogate the expression of ribosomal proteins from purified hematopoietic stems cells from patients with low risk myelodysplastic syndrome and age-matched healthy controls.
2011-08-14 | GSE30201 | GEO