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Series GSE126319 Query DataSets for GSE126319
Status Public on Oct 03, 2019
Title Variant and cell-context specific H3K27M reprogramming results in distinct enhancer architecture and oncogenic states
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Other
Summary Diffuse intrinsic pontine glioma (DIPG) is a fatal malignancy of the childhood pons characterized by a unique lysine-to-methionine substitution in histone-3 at lysine 27 (H3K27M). We show here that the specific Polycomb targets disrupted by H3K27M and resultant oncogenic state is dependent on both the variant of histone-3 and the cell- context in which the mutation occurs. Through primary DIPG tumor characterization and isogenic expression, we show that the same H3K27M mutation displays distinct modes of oncogenic reprogramming and establishes distinct enhancer architecture depending on whether it occurs in genes encoding H3.3 or H3.1. By comparison to non-malignant pediatric pontine tissue, we create a molecular map for DIPG, identifying and functionally validating both shared and subgroup-specific pathophysiology. Directly comparing the earliest events of H3K27M tumor initiation in putative cells-of-origin demonstrates that DIPG arises only from an oligodendrocyte precursor cell state.
 
Overall design H3K27Ac profiling of 30 primary DIPG and normal pontine tissue samples. Omni-ATAC profiling of 9 primary samples. RNA-seq profiling of 10 primary samples. ChIP-seq profiling of 12 patient-derived DIPG cultures. Multiple histone and TF ChIP-seq profiling of 5 stages of iPSC differentiation in the presence or absence of H3K27M. There are no restrictions or privacy issues. They were obtained under informed consent under an IRB protocol and have been fully deidentified.

Gene expression was quantified in "cnmc842t" primary human DIPG tumor sample and "pons02" primary human non-tumor pontine sample. RNA was sequenced on the Illumina NextSeq 500 and tpm values were quantified using featureCounts (Liao et al, 2014). Due to patient privacy concerns, we are witholding raw sequencing files at this time.
 
Contributor(s) Nagaraja S, Quezada M, Mancusi R, Monje M
Citation(s) 31588023
Submission date Feb 08, 2019
Last update date Jan 25, 2023
Contact name Michelle Monje
E-mail(s) mmonje@stanford.edu
Organization name Stanford University
Street address 265 Campus Drive, SIM1 G3035
City Stanford
State/province CA
ZIP/Postal code 94305
Country USA
 
Platforms (3)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL20795 HiSeq X Ten (Homo sapiens)
Samples (155)
GSM3596186 dipg4p End-repair and A-tailing
GSM3596187 dipg12p End-repair and A-tailing
GSM3596188 dipg14p End-repair and A-tailing
Relations
BioProject PRJNA521542
SRA SRP184732

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE126319_RAW.tar 90.4 Gb (http)(custom) TAR (of BW, VCF)
GSE126319_cnmc842t_pons02_tpm.csv.gz 362.1 Kb (ftp)(http) CSV
GSE126319_prc-d14-rna.tpm.xlsx 1.6 Mb (ftp)(http) XLSX
GSE126319_prc-d55-rna.tpm.xlsx 2.3 Mb (ftp)(http) XLSX
GSE126319_primary_dipg-rna.tpm.xlsx 3.5 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data provided as supplementary file
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