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Expression Analysis of dic(1 7)(q10 p10) in Myelodysplastic Syndromes (MDS) compared to control cohort and therapy-related Myeloid Neoplasms (t-MN)

ABSTRACT: Expression Analysis of dic(1 7)(q10 p10) in Myelodysplastic Syndromes (MDS) compared to control cohort and therapy-related Myeloid Neoplasms (t-MN)

PROVIDER: PRJNA485753 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7688940.fastq.gz	Fastqsanger.gz
	SRR7688941.fastq.gz	Fastqsanger.gz
	SRR7688932.fastq.gz	Fastqsanger.gz
	SRR7688942.fastq.gz	Fastqsanger.gz
	SRR7688933.fastq.gz	Fastqsanger.gz

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Expression Analysis of dic(1;7)(q10;p10) in Myelodysplastic Syndromes (MDS) compared to control cohort and therapy-related Myeloid Neoplasms (t-MN)

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

Affymetrix SNP array data for dic(1;7)(q10;p10) in Myelodysplastic Syndromes (MDS)

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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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Expression data from MDS patients with der(1;7)(q10;p10)

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

Affymetrix SNP array data for dic(1 7)(q10 p10) in Myelodysplastic Syndromes (MDS)

Project description:Affymetrix SNP array data for dic(1 7)(q10 p10) in Myelodysplastic Syndromes (MDS)

| PRJNA485752 | ENA

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)

Project description: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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Affymetrix SNP array data for myelodysplastic syndromes (MDS) and related neoplasms

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.

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Favorable prognostic phenotype in myelodysplastic syndrome with der(1;7)(q10;p10).

Project description:Unbalanced translocation der(1;7)(q10;p10) is a characteristic chromosomal abnormality in myelodysplastic syndrome (MDS). The current study revealed that among 13 MDS patients with der(1;7)(q10;p10), seven cases with no apparent dysplasia also had low numbers of myeloblasts in the bone marrow and a 3-year survival rate of 86%; in contrast, the remaining six cases had a 3-year survival rate of 0% (P = .003). It was therefore suggested that MDS patients with der(1;7)(q10;p10) are classified into a distinct group with a favorable prognosis and another distinct group with a very poor prognosis.

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Q10

Project description:Q10

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