|
|
GEO help: Mouse over screen elements for information. |
|
Status |
Public on May 01, 2024 |
Title |
Clonal evolution of the 3D chromatin landscape of relapsed ALL [ATAC-seq] |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
Summary |
Relapsed pediatric B-cell acute lymphoblastic leukemia (B-ALL) remains one of the leading causes of cancer mortality in children. Up to 20% of children will suffer relapse and face a poor prognosis. Our recent work on the evolution of the epigenetic landscape from diagnosis to relapse demonstrates both substantial diversity in the chromatin landscape as well as shared relapse-specific superenhancer activation, highlighting the importance of chromatin changes in disease progression. However, there is a gap in our understanding of B-ALL progression through the lens of three-dimensional (3D) chromosome topology. To uncover 3D chromatin architecture-related mechanisms underlying drug resistance in B-ALL, we performed Hi-C, ATAC-seq, and RNA-seq on 12 matched primary pediatric leukemia specimens at diagnosis and relapse. Mapping of structural variations (SVs) using Hi-C data revealed previously unidentified stable, diagnosis-specific, and relapse-specific SVs providing further evidence for clonal evolution as a mechanism for drug resistance. Moreover, Hi-C analysis revealed genome wide chromatin remodeling specifically in terms of A/B compartments, TAD interactivity, and chromatin loops. Integration with ATAC-seq and RNA-seq datasets revealed strong correlation with both gene expression and chromatin accessibility. Additionally, we identified recurrent A/B compartments and TAD interactivity changes across the patient cohort for which we were able to demonstrate a crucial role in the clonal evolution of B-ALL. Shared changes in 3D genome organization drive the expression of genes/pathways previously implicated in drug resistance as well. Lastly, enrichment analysis revealed key upstream regulators of 3D genome architecture in B-ALL disease progression. These results extend the landscape of genetic alterations in relapsed B-ALL through the addition of the 3D genomic landscape and identify a breadth of novel therapeutic targets.
|
|
|
Overall design |
Comparative gene expression profiling analysis of RNA-seq data from 12 matched primary pediatric leukemia specimens at diagnosis and relapse.
|
|
|
Contributor(s) |
Narang S, Ghebrechristos Y, Evensen NA, Jasinski S, Ostrow TH, Witkowski M, Aifantis I, Tsirigos A, Carroll WL |
Citation(s) |
39198446 |
|
Submission date |
Jan 11, 2023 |
Last update date |
Sep 27, 2024 |
Contact name |
Sonali Narang |
E-mail(s) |
sonali.narang@nyulangone.org
|
Phone |
5169652665
|
Organization name |
NYU Langone
|
Street address |
435 east 30th street
|
City |
New York |
State/province |
NY |
ZIP/Postal code |
10016 |
Country |
USA |
|
|
Platforms (1) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
Samples (24)
|
|
This SubSeries is part of SuperSeries: |
GSE222687 |
Clonal evolution of the 3D chromatin landscape of relapsed ALL |
|
Relations |
BioProject |
PRJNA923005 |
Supplementary file |
Size |
Download |
File type/resource |
GSE222675_RAW.tar |
8.3 Gb |
(http)(custom) |
TAR (of BED, BW) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
|
|
|
|
|