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Focal deletions of a promoter tether activate the IRX3 oncogene in T-cell acute lymphoblastic leukemia [UMI4C]

GSE279521 Homo sapiens (human) Other 13 samples Submitted 2024/10/20 Platform GPL15520
At a glance

human · 13 samples

Organism
Homo sapiens (human)
Topic
Acute lymphoblastic leukemiaThis series is part of our curated briefing on it.
Samples
13 samples: 3 × UMI4C_PF-382_FTOint8_CTCFbait_tech vs 3 × UMI4C_PF-382_IRX3_CTCF3pbait_tech vs 3 × UMI4C_PF-382_IRX3_CTCF5pbait_techGroups 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
Focal deletions of a promoter tether activate the IRX3 oncogene in T-cell acute lymphoblastic leukemiaBlood · 2024
Summary (written by the submitters)
Oncogenes can be activated in cis through multiple mechanisms including enhancer hijacking events and noncoding mutations that create enhancers or promoters de novo. These paradigms have helped parse somatic variation of noncoding cancer genomes, thereby providing a rationale to identify noncanonical mechanisms of gene activation. Here we describe a novel mechanism of oncogene activation whereby focal copy number loss of an intronic element within the FTO gene leads to aberrant expression of IRX3, an oncogene in T cell acute lymphoblastic leukemia (T-ALL).
Read the full summary ↓
Loss of this CTCF bound element downstream to IRX3 (+224 kb) leads to enhancer hijack of an upstream developmentally active super-enhancer of the CRNDE long noncoding RNA (-644 kb). Unexpectedly, the CRNDE super-enhancer interacts with the IRX3 promoter with no transcriptional output until it is untethered from the FTO intronic site. We propose that 'promoter tethering' of oncogenes to inert regions of the genome is a previously unappreciated biological mechanism preventing tumorigenesis.
Published in
Focal deletions of a promoter tether activate the IRX3 oncogene in T-cell acute lymphoblastic leukemia
Rahman S, Bloye G, Farah N et al. · Blood 2024 · PMID 39316719 · doi:10.1182/blood.2024024300
This dataset
Open GSE279521 in finder → Find more human datasets → Acute lymphoblastic leukemia landscape →
Download · which file do I need?

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.

Series matrix ↓
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 (GSE279521_RAW.tar), including the raw array or instrument files. Can be large; the picker in step 2 takes just the samples you need.

Whole study · RAW.tar ↓

Also filed as BioProject PRJNA1173185. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39316719) ↗
Study design
3 × UMI4C_PF-382_FTOint8_CTCFbait_tech vs 3 × UMI4C_PF-382_IRX3_CTCF3pbait_tech vs 3 × UMI4C_PF-382_IRX3_CTCF5pbait_tech

Supports a between-group comparison across 9 samples.

How we read this: 3 replicated groups read from 13 sample titles; they account for 9 of them. 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
More Acute lymphoblastic leukemia datasets

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