Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Patient-Derived Orthotopic Xenografts and Cell Lines from Pediatric High-Grade Glioma Recapitulate Heterogeneity of Histopathology, Molecular Signatures and Drug Response

ABSTRACT: We established 21 patient-derived pHGG orthotopic xenograft (PDOX) models and 8 matched cell lines from diverse pHGG subgroups. Models recapitulated histopathology, DNA methylation signatures, mutations and gene expression patterns of the patient tumors from which they were derived, and included rare subgroups not well-represented by existing models. We also included 6 DIPG cell lines generously shared by Dr. Michelle Monje (Stanford University). An online interactive data portal is available to explore associated detailed molecular characterization and HTS chemical sensitivity data.

ORGANISM(S): Homo sapiens

PROVIDER: GSE152035 | GEO | 2020/12/09

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

A biobank of 30 molecularly characterized patient-derived xeongraft models of pediatric brain tumors [Illumina HumanMethylation]

Project description:We have generated and comprehensively characterized 30 patient-derived orthotopic xenograft (PDOX) models and 7 cell lines represeneting subgroups of medulloblastoma, high-grade glioma, atypical teratoid/rhabdoid tumor, ependymoma and pineoblastoma.

2018-10-25 | GSE99994 | GEO

A biobank of 30 molecularly characterized patient-derived xeongraft models of pediatric brain tumors [Affymetrix]

2018-10-25 | GSE99961 | GEO

Capmatinib shows superior efficacy for MET-fusion driven pediatric high-grade glioma and synergizes with radiotherapy (mouse methylation array)

Project description:Background: Pediatric high-grade glioma (pHGG) is the most frequent malignant brain tumor in children and can be subclassified into multiple entities. Fusion genes activating the MET receptor tyrosine kinase often occur in infant-type hemispheric glioma (IHG) but also in other pHGGs, and are associated with devastating morbidity and mortality. Methods: To identify new treatment options, we established and characterized two novel orthotopic mouse models harboring distinct MET fusions. These included an immunocompetent, murine allograft model and patient-derived orthotopic xenografts (PDOX) from a MET-fusion iHG patient who failed conventional therapy and targeted therapy with cabozantinib. With these models, we analyzed the efficacy and pharmacokinetic properties of three MET inhibitors, capmatinib, crizotinib and cabozantinib, alone or combined with radiotherapy (RT). Results: The PDOX models recapitulated the poor efficacy of cabozantinib experienced by the patient. In contrast, capmatinib showed superior brain pharmacokinetic properties and greater in vitro and in vivo efficacy than cabozantinib or crizotinib. Strikingly, capmatinib treated mice displayed long-term progression-free survival (PFS) when combined with radiotherapy in two complementary mouse models. Molecular analysis of the treated tumors revealed impaired DNA repair after MET inhibition as a plausible mechanism of radiosensitization Conclusions: We comprehensively investigated the combination of MET inhibition and radiotherapy as a novel treatment option for MET-driven pHGG. Our seminal preclinical data package includes pharmacokinetic characterization, recapitulation of clinical outcomes, coinciding results from multiple complementing in vivo studies and a plausible molecular mechanism. We thereby demonstrate the groundbreaking efficacy of capmatinib and radiation, as a highly promising concept for future clinical trials.

2024-06-12 | GSE252500 | GEO

Capmatinib shows superior efficacy for MET-fusion driven pediatric high-grade glioma and synergizes with radiotherapy [RNA-seq]

Project description:Pediatric high-grade glioma (pHGG) is the most frequent malignant brain tumor in children and can be subclassified into multiple entities. Fusion genes activating the MET receptor tyrosine kinase often occur in infant-type hemispheric glioma (iHG) but also in other pHGGs, and are associated with devastating morbidity and mortality. To identify new treatment options, we established and characterized two novel orthotopic mouse models harboring distinct MET fusions. These included an immunocompetent, murine allograft model and patient-derived orthotopic xenografts (PDOX) from a MET-fusion iHG patient who failed conventional therapy and targeted therapy with cabozantinib. With these models, we analyzed the efficacy and pharmacokinetic properties of three MET inhibitors, capmatinib, crizotinib and cabozantinib, alone or combined with radiotherapy (RT). The PDOX models recapitulated the poor efficacy of cabozantinib experienced by the patient. In contrast, capmatinib showed superior brain pharmacokinetic properties and greater in vitro and in vivo efficacy than cabozantinib or crizotinib. Strikingly, capmatinib treated mice displayed long-term progression-free survival (PFS) when combined with radiotherapy in two complementary mouse models. Molecular analysis of the treated tumors revealed impaired DNA repair after MET inhibition as a plausible mechanism of radiosensitization. We comprehensively investigated the combination of MET inhibition and radiotherapy as a novel treatment option for MET-driven pHGG. Our seminal preclinical data package includes pharmacokinetic characterization, recapitulation of clinical outcomes, coinciding results from multiple complementing in vivo studies and a plausible molecular mechanism. We thereby demonstrate the groundbreaking efficacy of capmatinib and radiation, as a highly promising concept for future clinical trials.

2024-06-12 | GSE247864 | GEO

Capmatinib shows superior efficacy for MET-fusion driven pediatric high-grade glioma and synergizes with radiotherapy [human methylation array]

2024-06-12 | GSE252458 | GEO

Comprehensive Mapping of Paediatric High Grade Glioma

Project description:Overall paediatric high grade glioma (pHGG) has a poor prognosis, in part due to the lack of understanding of the underlying biology. We therefore used high resolution 244k oligo array comparative genomic hybridisation (oligo aCGH) (Agilent Technologies) to analyse DNA from 38 formalin-fixed paraffin embedded pHGG samples, including 13 DIPG (ten pre-treatment samples and three post-mortem). The pattern of gains and losses were distinct from those seen in HGG arising in adults. In particular we found 1q gain in 22% of our cohort compared to 9% in adults. Homozygous loss at 8p12 was seen in 6/38 (15%) of pHGG. This deletion has not been previously reported in adult or paediatric high grade gliomas. The minimal deleted region is of the gene ADAM3A and homozygous deletion of ADAM3A was confirmed by quantitative real time PCR (qPCR). This novel homozygous deletion of ADAM3A in pHGG merits further study. Loss of CDKN2A/CDKN2B was seen in 4/38 (10%) samples by oligo a CGH, confirmed by FISH on TMAs and was restricted to supratentorial tumours. Amplification of the 4q11-13 region was detected in 8% of cases and included PDGFRA and KIT, subsequent qPCR analysis was consistent with amplification of PDGFRA. MYCN amplification was seen in 2/38 samples (5%) and was shown to be significantly associated with anaplastic astrocytomas (p=0.03). Overall DIPG shared similar spectrum of changes to supratentorial HGG with some notable differences including high frequency of 17p loss and 14q loss and lack of CDKN2A/CDKN2B deletion. To our knowledge, this study examines the largest DIPG cohort to date using high-throughput genetic techniques. 38 high grade glioma samples including 13 DIPG (ten pre-treatment samples and three post-mortem) analysed by Agilent 244K array CGH. Samples BSG 1, 2, 3, 5, 6, 7, 8, 9, 10 and 11 are the ten pre-treatment DIPG samples. Samples BSG 4, 12 and 13 are the three post-treatment DIPG samples.

2010-12-01 | E-GEOD-21420 | biostudies-arrayexpress

RNA-seq bam

Project description:We established 21 patient-derived pHGG orthotopic xenograft (PDOX) models and eight matched cell lines from diverse groups of pHGG. Here are all available RNA Sequencing (RNA-seq) data from patient tumor, PDOX, and cell lines from our study.

| EGAS00001005161 | EGA

WES bam

Project description:We established 21 patient-derived pHGG orthotopic xenograft (PDOX) models and eight matched cell lines from diverse groups of pHGG. Here are all available Whole Exome Sequencing (WES) data from patient tumor, PDOX, and cell lines from our study.

| EGAS00001005160 | EGA

WGS bam

Project description:We established 21 patient-derived pHGG orthotopic xenograft (PDOX) models and eight matched cell lines from diverse groups of pHGG. Here are all available Whole Genome Sequencing (WGS) data from patient tumor, PDOX, and cell lines from our study.

| EGAS00001005159 | EGA

Patient specific orthotopic glioblastoma xenograft models recapitulate the histopathology and biology of human glioblastomas in situ (CGH)

Project description:Frequent discrepancies between preclinical and clinical results of anti-cancer agents demand a reliable translational platform that can precisely recapitulate the biology of human cancers. Another critical unmet need is the ability to predict therapeutic responses for individual patients. Toward this goal, we have established a library of orthotopic glioblastoma (GBM) xenograft models using surgical samples of GBM patients. These patient-specific GBM xenograft tumors recapitulate histopathological properties and maintain genomic characteristics of parental GBMs in situ. Furthermore, in vivo irradiation, chemotherapy, and targeted therapy of these xenograft tumors mimic the treatment response of parental GBMs. We also found that establishment of orthotopic xenograft models portends poor prognosis of GBM patients and identified the gene signatures and pathways signatures associated with the clinical aggressiveness of GBMs. Together, the patient-specific orthotopic GBM xenograft library represent the preclinically and clinically valuable “patient tumor’s phenocopy” that represents molecular and functional heterogeneity of GBMs. aCGH experiments were performed for a human glioblastoma tissue (sample ID: PC-NS08-559) and the matching xenograft tumor tissue using the Agilent Human Whole Genome CGH 244K microarray according to manufacturer's protocol (2-color).

2013-01-18 | E-GEOD-42577 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data