|
| Status |
Public on Sep 01, 2019 |
| Title |
Affymetrix SNP array data for dic(1;7)(q10;p10) in Myelodysplastic Syndromes (MDS) |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by SNP array
|
| Summary |
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.
|
| |
|
| Overall design |
Copy number analysis of Affymetrix 100K and 500K SNP arrays was performed for 5 dic(1;7)(q10;p10) MDS cases
|
| |
|
| Contributor(s) |
Mecucci C, Figueroa ME, Barba G, Pierini V, Lema Fernandez AG |
| Citation(s) |
30923319 |
| Submission date |
Aug 13, 2018 |
| Last update date |
Dec 02, 2019 |
| Contact name |
Cristina Mecucci |
| E-mail(s) |
cristina.mecucci@unipg.it
|
| Phone |
+39 075 5783808
|
| Organization name |
University of Perugia
|
| Department |
Department of Medicine, Hematology and Bone Marrow Transplantation Unit
|
| Lab |
Laboratory of Cytogenetics and Molecular Genetics
|
| Street address |
Piazzale Menghini n.9
|
| City |
Perugia |
| ZIP/Postal code |
06132 |
| Country |
Italy |
| |
|
| Platforms (1) |
| GPL16131 |
[CytoScanHD_Array] Affymetrix CytoScan HD Array |
|
| Samples (5)
|
|
| This SubSeries is part of SuperSeries: |
| GSE118648 |
A Distinct Epigenetic Program Underlies the 1;7 Translocation in Myelodysplastic Syndromes (MDS) |
|
| Relations |
| BioProject |
PRJNA485752 |
Less...
More...