Study
H3.3G34R/V-transformed interneuron progenitors co-opt PDGFRA for gliomagenesis
Study ID | Alternative Stable ID | Type |
---|---|---|
EGAS00001004301 | Other |
Study Description
Histone H3.3 glycine 34 to arginine/valine (H3.3G34R/V) mutations occur in deadly hemispheric high-grade gliomas. These tumors show exquisite regional and temporal specificity, suggesting a developmental context permissive to the effects of G34R/V mutations. Here we present the molecular landscape of G34R/V gliomas (n=85) and show that 50% bear activating mutations in PDGFRA, with strong selection pressure for PDGFRAMUT clones at recurrence. We show that G34R/V tumors arise in interneuron progenitors of the foetal ventral forebrain expressing GSX2 and the DLX family of homeobox transcription factors, where terminal neuronal differentiation is impaired through aberrant G34R/V-mediated H3K27me3. Frequent co-occurrence of G34R/V & PDGFRAMUT is facilitated in this interneuron lineage-of-origin as PDGFRA forms an aberrant chromatin loop with the adjacent GSX2, hijacking its active chromatin conformation. At the single-cell level, G34R/V tumours entirely lack oligodendroglial transcriptional programs prominent in other glioma entities, and instead harbour dual neuronal and astroglial ... (Show More)
Study Datasets 4 datasets.
Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data
Dataset ID | Description | Technology | Samples |
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EGAD00001006097 |
We profiled 16 high-grade gliomas patient tumour samples by single-cell and single-nuclei RNA-seq and 3 normal-matched single-cell RNA-seq using 10X Chromium 3'. The fastq files are provided.
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Illumina HiSeq 4000,Illumina NovaSeq 6000 | 21 |
EGAD00001006098 |
We profiled 18 high-grade gliomas patient tumor samples by bulk RNA-seq. The raw fastqs are provided.
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Illumina HiSeq 2000,Illumina HiSeq 4000,Illumina NovaSeq 6000,unspecified | 20 |
EGAD00001006099 |
We profiled 23 high-grade gliomas patient tumor samples and 4 normal-matched patient samples by whole exome sequencing. The raw fastq files are provided.
|
Illumina HiSeq 2000,Illumina HiSeq 2500,Illumina HiSeq 4000,unspecified | 27 |
EGAD00001006100 |
We profiled 16 patient tumour samples by ChIP-seq. H3K27ac and Input are provided for 16 samples and H3K27me3 is provided for 14 samples.
Among the 16 samples, 9 are G34WT and 7 are G34R/V. The raw fastq or bam files are provided.
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Illumina HiSeq 2000,Illumina HiSeq 2500,Illumina NovaSeq 6000 | 78 |
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