Next Generation Sequencing of Diffuse Intrinsic Pontine Glioma Samples
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA431328 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Next Generation Sequencing of Diffuse Intrinsic Pontine Glioma Samples
| PRJNA431329 | ENA
Project description:Diffuse intrinsic pontine glioma (DIPG), a lethal pediatric cancer driven by H3K27M oncohistones, exhibits aberrant epigenetic regulation and stem-like cell states. Here, we uncover an axis involving H3.3K27M oncohistones, CREB5/ID1, which sustains the stem-like state of DIPG cells, promoting malignancy. We demonstrate that CREB5 mediates elevated ID1 levels in the H3.3K27M/ACVR1WT subtype, promoting tumor growth; while BMP signaling regulates this process in the H3.1K27M/ACVR1MUT subtype. Furthermore, we reveal that H3.3K27M directly enhances CREB5 expression by reshaping the H3K27me3 landscape at the CREB5 locus, particularly at super-enhancer regions. Additionally, we elucidate the collaboration between CREB5 and BRG1, the SWI/SNF chromatin remodeling complex catalytic subunit, in driving oncogenic transcriptional changes in H3.3K27M DIPG. Intriguingly, disrupting CREB5 super-enhancers with ABBV-075 significantly reduces its expression and inhibits H3.3K27M DIPG tumor growth. Combined treatment with ABBV-075 and a BRG1 inhibitor presents a promising therapeutic strategy for clinical translation in H3.3K27M DIPG treatment.
2025-01-28 | PXD053094 | Pride
Project description:Diffuse intrinsic pontine glioma (DIPG), a lethal pediatric cancer driven by H3K27M oncohistones, exhibits aberrant epigenetic regulation and stem-like cell states. Here, we uncover an axis involving H3.3K27M oncohistones, CREB5/ID1, which sustains the stem-like state of DIPG cells, promoting malignancy. We demonstrate that CREB5 mediates elevated ID1 levels in the H3.3K27M/ACVR1WT subtype, promoting tumor growth; while BMP signaling regulates this process in the H3.1K27M/ACVR1MUT subtype. Furthermore, we reveal that H3.3K27M directly enhances CREB5 expression by reshaping the H3K27me3 landscape at the CREB5 locus, particularly at super-enhancer regions. Additionally, we elucidate the collaboration between CREB5 and BRG1, the SWI/SNF chromatin remodeling complex catalytic subunit, in driving oncogenic transcriptional changes in H3.3K27M DIPG. Intriguingly, disrupting CREB5 super-enhancers with ABBV-075 significantly reduces its expression and inhibits H3.3K27M DIPG tumor growth. Combined treatment with ABBV-075 and a BRG1 inhibitor presents a promising therapeutic strategy for clinical translation in H3.3K27M DIPG treatment.
2025-01-28 | PXD060271 | Pride
Project description:<p>Diffuse intrinsic pontine glioma (DIPG) is an extremely rare (~350 cases/year) and universally fatal childhood brain cancer. Standard clinical strategies such as chemotherapy and radiotherapy show only transient improvement in patient condition and result in negligible change in survival, DIPG remains at below 1% survival after 5 years. Prioritization of panobinostat through previous cooperative work resulted in a phase 1 clinical trial. Nonetheless, new therapies for DIPG must be identified to further dramatically change the statistics for DIPG.</p> <p>To identify novel therapy strategies for DIPG, we performed whole exome(16 new samples, 22 previously published samples, 38 in total with 26 matched normal) and RNA deep sequencing (17 new samples, 11 previously published samples) on a cohort of new patient samples. Sequencing results aid in the identification of recurrent mutations/variations and endotypic expression profiling to identify new therapeutic and treatment strategies for DIPG. </p>
| phs001526 | dbGaP
Project description:Non-inflammatory tumor microenvironment of Diffuse Intrinsic Pontine Glioma (DIPG)
| PRJNA474825 | ENA
Project description:Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric brain tumor with limited therapeutic options. The majority of cases of DIPG exhibit a mutation in histone 3 (H3K27M) that results in oncogenic transcriptional aberrancies. We show here that DIPG is vulnerable to transcriptional disruption using either bromodomain inhibition or CDK7 blockade. We observe that targeting oncogenic transcription through either of these methods synergizes with HDAC inhibition and that DIPG cells resistant to HDAC inhibitor therapy retain sensitivity to CDK7 blockade. Furthermore, identification of super-enhancers in DIPG provides insights toward the cell of origin, highlighting oligodendroglial lineage genes, and reveals unexpected mechanisms mediating tumor viability and invasion, including potassium channel function and EPH-ephrin signaling. The findings presented here demonstrate transcriptional vulnerabilities of DIPG and elucidate previously unknown mechanisms of DIPG pathobiology.
2017-04-21 | GSE94259 | GEO
Project description:We report the application of chromatin immunoprecipitation for high-thoughput profiling of RNA polymerase II and histone modifications (H3K27me3 and H3K27ac) in diffuse intrinsic pontine glioma cells (DIPG) in response to CDK9 inhibition
2020-04-12 | GSE129777 | GEO
Project description:Diffuse Intrinsic Pontine Glioma (DIPG) is a rare and highly aggressive pediatric tumor. The average survival time after diagnosis is less than one year. Currently, there are no effective treatments. Characteristic of DIPG is a mutation in histone H3 which leads to a substitution of Lysine 27 to Methionine (H3K27M) which deregulates Polycomb Repressive Complex 2 (PRC2), including enzymatic activity of EZH2. Previous studies have shown that inhibition of EZH2 by chemical agents decreases DIPG cell proliferation and inhibits tumor growth in vivo. My thesis project aims to confirm that EZH2 could be a therapeutic target using chemical EZH2 inhibitors, small interfering RNAs and a CRISPR/Cas9 approach in a series of DIPG tumor cell lines and to determine underlying molecular mechanisms of action.
2022-04-01 | PXD017525 | Pride
Project description:Diffuse midline glioma (DMG) identifies gliomas originating in the thalami, brainstem, cerebellum and spine. Within this entity, tumours that infiltrate the pons, called diffuse intrinsic pontine gliomas (DIPGs), have a rapid onset and devastating neurological symptoms. Radiotherapy is the only intervention that is able to modify the disease course, albeit not in a curative way. In recent years, liquid biopsies have represented the next step in clinical diagnostics due to their easily accessible nature. The purpose of this study is to profile circulating miRNA expression to disclose a potential prognostic signature with clinical impact.
2022-12-21 | GSE160249 | GEO
Project description:Purpose: More than 90% of children with diffuse intrinsic pontine glioma (DIPG) die within 2 years of diagnosis. There is a dire need to identify therapeutic targets, however lack of patient material for research has limited progress. We evaluated a large cohort of diffuse intrinsic pontine gliomas (DIPGs) to identify recurrent genomic abnormalities and gene expression signatures underlying DIPG. Patients and Methods: We used single nucleotide polymorphism arrays to evaluate genomic copy number imbalances in 43 DIPGs from 40 patients and in 8 low-grade exophytic brainstem gliomas. Gene expression arrays were used to evaluate expression signatures from 27 DIPGs, 6 low-grade exophytic brainstem gliomas and 66 low-grade gliomas arising outside the brainstem. Results: Frequencies of specific large-scale and focal imbalances varied significantly between DIPGs and pediatric glioblastomas outside the brainstem. Focal amplifications of genes within the receptor tyrosine kinase-Ras-PI3-kinase signaling pathway were found in 47% of DIPG, with PDGFRA and MET showing the highest frequency. 30% of DIPG contained focal amplifications of cell-cycle regulatory genes controlling RB phosphorylation, and 21% had concurrent amplification of genes from both pathways. Some tumors showed heterogeneity in amplification patterns. DIPGs showed distinct gene expression signatures relating to developmental processes compared to pediatric glioblastomas arising outside the brainstem, while expression signatures of low-grade exophytic brainstem gliomas were similar to low-grade gliomas outside the brainstem. Copy number analaysis: 43 DIPG samples, 8 Low Grade Gliomas using SNP6.0. Available matched normals are also profiled with SNP6.0. Expression analysis: 29 DIPG samples, 6 Low grade samples Please contact Suzanne Baker at Suzanne.Baker@stjude.org for CEL files and genotype calls.
2011-09-20 | E-GEOD-26576 | biostudies-arrayexpress