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
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.
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.
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.
Illumina HiSeq 2000,Illumina HiSeq 2500,Illumina NovaSeq 6000 78

Who archives the data?

There are no publications available