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Clonal evolution of the 3D chromatin landscape of relapsed ALL [Hi-C]

GSE222679 Homo sapiens (human) Other 24 samples Submitted 2024/05/01 Platform GPL24676
At a glance

human · 24 samples

Organism
Homo sapiens (human)
Samples
24 samples: 24 samples, each with a distinct title — no replicated groupsGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI.
Paper
Clonal evolution of the 3D chromatin landscape in patients with relapsed pediatric B-cell acute lymphoblastic leukemiaNature communications · 2024
Summary (written by the submitters)
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.
Read the full summary ↓
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.
Published in
Clonal evolution of the 3D chromatin landscape in patients with relapsed pediatric B-cell acute lymphoblastic leukemia
Narang S, Ghebrechristos Y, Evensen NA et al. · Nature communications 2024 · PMID 39198446 · doi:10.1038/s41467-024-51492-6
This dataset
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Direct links to NCBI, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need.

All supplementary files ↗
3 · The original raw files

Whole study · RAW.tar

Everything the authors deposited as one archive (GSE222679_RAW.tar), including the raw array or instrument files. Can be large; the picker in step 2 takes just the samples you need.

Also filed as BioProject PRJNA923008. Searching any of these in the dataset finder brings you back here.

Study design
24 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 24 sample titles: 24 distinct titles with little repetition. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
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