Evidence
![](https://psychiatryai.com/wp-content/uploads/2023/04/psychiatryai_com.webp)
Nat Commun. 2023 Nov 24;14(1):7717. doi: 10.1038/s41467-023-43564-w.
ABSTRACT
Pediatric high-grade gliomas of the subclass MYCN (HGG-MYCN) are highly aggressive tumors frequently carrying MYCN amplifications, TP53 mutations, or both alterations. Due to their rarity, such tumors have only recently been identified as a distinct entity, and biological as well as clinical characteristics have not been addressed specifically. To gain insights into tumorigenesis and molecular profiles of these tumors, and to ultimately suggest alternative treatment options, we generated a genetically engineered mouse model by breeding hGFAP-cre::Trp53Fl/Fl::lsl-MYCN mice. All mice developed aggressive forebrain tumors early in their lifetime that mimic human HGG-MYCN regarding histology, DNA methylation, and gene expression. Single-cell RNA sequencing revealed a high intratumoral heterogeneity with neuronal and oligodendroglial lineage signatures. High-throughput drug screening using both mouse and human tumor cells finally indicated high efficacy of Doxorubicin, Irinotecan, and Etoposide as possible therapy options that children with HGG-MYCN might benefit from.
PMID:38001143 | DOI:10.1038/s41467-023-43564-w
![Google](https://www.google.com/images/branding/googlelogo/2x/googlelogo_light_color_92x30dp.png)
![Google Keep](https://www.gstatic.com/images/branding/product/1x/keep_48dp.png)
![Share on Linkedin](https://psychiatryai.com/wp-content/uploads/2023/10/linkedin-logo-png-2048-1.png)
Estimated reading time: 3 minute(s)
Latest: Psychiatryai.com #RAISR4D Evidence
![](/wp-content/uploads/2024/04/bd462cc11bcf0bd0d0d6f1d0f8b7cd04-modified-1.png)
Cool Evidence: Engaging Young People and Students in Real-World Evidence
![](/wp-content/uploads/2024/04/bd462cc11bcf0bd0d0d6f1d0f8b7cd04-modified-1.png)
Real-Time Evidence Search [Psychiatry]
![](/wp-content/uploads/2024/04/pubmed.png)
AI Research
![](/wp-content/uploads/2024/05/Il5nR_nf_400x400-modified-1.png)
Mouse models of pediatric high-grade gliomas with MYCN amplification reveal intratumoral heterogeneity and lineage signatures
![](https://psychiatryai.com/wp-content/uploads/2023/04/psychiatryai_com.webp)
🌐 90 Days
AI Virtual Reality Related Evidence Matrix
Ependymomas of the spinal region in adults: Clinical and pathological features and MYCN expression levels in spinal ependymomas and myxopapillary ependymomas A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations A prognostic neural epigenetic signature in high-grade glioma Malignant glioma in L-2-Hydroxyglutaric Aciduria: thorough molecular characterization of a case and literature review Gliomatosis cerebri in children: A poor prognostic phenotype of diffuse gliomas with a distinct molecular profile Glioma pH-responsive targeted nanoparticles release ERK-inhibitor in the hypoxic zone and sensitize free gemcitabine in mutant K-Ras-addicted pancreatic cancer cells and mouse model Systematic analysis of RNA-binding proteins identifies targetable therapeutic vulnerabilities in osteosarcoma Pediatric CNS tumors and 2021 WHO classification: what do oncologists need from pathologists? Proteomic Analysis of Spatial Heterogeneity Identifies HMGB2 as Putative Biomarker of Tumor Progression in Adult-Type Diffuse Astrocytomas Native-state proteomics of Parvalbumin interneurons identifies unique molecular signatures and vulnerabilities to early Alzheimer's pathology Isocitrate Dehydrogenase 1/2 Wildtype Adult Astrocytoma with WHO Grade 2/3 Histological Features: Molecular Re-Classification, Prognostic Factors, Clinical Outcomes Childhood cancer mutagenesis caused by transposase-derived PGBD5 CNS tumors with PLAGL1-fusion: beyond ZFTA and YAP1 in the genetic spectrum of supratentorial ependymomas Fully automated MR-based virtual biopsy of primary CNS lymphomas 7 Tesla magnetic resonance spectroscopic imaging predicting IDH status and glioma grading Assessing transcriptomic heterogeneity of single-cell RNASeq data by bulk-level gene expression data Lineage specification in glioblastoma is regulated by METTL7B Ependymoma from Benign to Highly Aggressive Diseases: A Review How to standardize the diagnostic approach to pituitary neuroendocrine tumors BCOR::CREBBP fusion in malignant neuroepithelial tumor of CNS expands the spectrum of methylation class CNS tumor with BCOR/BCOR(L1)-fusion The Clinical Utility of a Tiered Approach to Pediatric Glioma Molecular Characterization for Resource-Limited Settings Imbalance in glucose metabolism regulates the transition of microglia from homeostasis to Disease Associated Microglia stage 1 Clinical implications of DNA methylation-based integrated classification of histologically defined grade 2 meningiomas Preclinical systemic pharmacokinetics, dose-proportionality, and CNS distribution of the ATM inhibitor WSD0628, a novel radiosensitizer for the treatment of brain tumors Clinical and genomic characterization of chemoradiation-resistant HPV-positive oropharyngeal squamous cell carcinoma Metabolic models predict fotemustine and the combination of eflornithine/rifamycin and adapalene/cannabidiol for the treatment of gliomas Histopathologic image-based deep learning classifier for predicting platinum-based treatment responses in high-grade serous ovarian cancer Exploring a distinct FGFR2::DLG5 rearrangement in a low-grade neuroepithelial tumor: A case report and mini-review of protein fusions in brain tumors Exploring a distinct FGFR2::DLG5 rearrangement in a low-grade neuroepithelial tumor: A case report and mini-review of protein fusions in brain tumors Perifocal edema is a risk factor for preoperative seizures in patients with meningioma WHO grade 2 and 3 Pediatric neuropathology practice in a low- and middle-income country: capacity building through institutional twinning Identification of senescent, TREM2-expressing microglia in aging and Alzheimer's disease model mouse brain Extensive Shrinkage and Long-term Stable Disease in a Teenage Female Patient With High-grade Glioma Treated With Temozolomide and Radiation in Combination With Oral Recombinant Methioninase and a Low-methionine Diet Headache in Brain Tumors An effective ensemble learning approach for classification of glioma grades based on novel MRI features End-to-End Multi-task Learning Architecture for Brain Tumor Analysis with Uncertainty Estimation in MRI Images Histoplasty Modification of the Tumor Microenvironment in a Murine Preclinical Model of Breast Cancer Biochemical, Biomarker, and Behavioral Characterization of the GrnR493X Mouse Model of Frontotemporal Dementia Immunoregulatory role of the gut microbiota in inflammatory depression Very Long-Term Survivorship in Pediatric DIPG: Case Report and Review of the Literature CPT1A loss disrupts BCAA metabolism to confer therapeutic vulnerability in TP53-mutated liver cancer Recurrent mutations in tumor suppressor FBXW7 bypass Wnt/beta-catenin addiction in cancer Meningioma: International Consortium on Meningiomas (ICOM) consensus review on scientific advances & treatment paradigms for clinicians, researchers, and patients Machine Learning in Diagnosis and Prognosis of Lung Cancer by PET-CT Colitis reduces active social engagement in mice and is ameliorated by supplementation with human microbiota members Brain high-throughput multi-omics data reveal molecular heterogeneity in Alzheimer's disease Stem Cell Markers in Neoplasms and their Relationship with Progression-free and Overall Survival in Patients with Recurrence Status epilepticus in patients with brain tumors and metastases: A multicenter cohort study of 208 patients and literature review TRIM24 Cooperates with Ras Mutation to Drive Glioma Progression through snoRNA Recruitment of PHAX and DNA-PKcs A comprehensive histomolecular characterization of meningioangiomatosis: Further evidence for a precursor neoplastic lesion Genetic profiles of oligometastatic non-small cell lung cancer and corresponding brain metastases Turning anecdotal irradiation-induced anticancer immune responses into reproducible in situ cancer vaccines via disulfiram/copper-mediated enhanced immunogenic cell death of breast cancer cells Forebrain EAAT3 overexpression increases susceptibility to amphetamine-induced repetitive behaviors Rebound growth of BRAF mutant pediatric glioma cells after MAPKi withdrawal is associated with MAPK reactivation and secretion of microglia-recruiting cytokines Rare dual-genotype IDH mutant glioma: Review of previously reported cases and two new cases of true "oligoastrocytoma" Author Correction: Using rare genetic mutations to revisit structural brain asymmetry Imaging-based Efficacy Evaluation of Cancer Immunotherapy in Engineered Tumor Platforms and Tumor Organoids The development of fatigue after treatment for pediatric brain tumors does not differ between tumor locations H3K27-Altered Diffuse Glioma of the Spinal Cord in Adult Patients: A Qualitative Systematic Review and Peculiarity of Radiological Findings Machine Learning-Assisted Classification of Paraffin-Embedded Brain Tumors with Raman Spectroscopy Advances in Clinical Application of Cerebrospinal Fluid Circulating Tumor DNA in Leptomeningeal Metastasis of Non-small Cell Lung Cancer Glioblastoma-instructed microglia transition to heterogeneous phenotypic states with phagocytic and dendritic cell-like features in patient tumors and patient-derived orthotopic xenografts Artificial intelligence in neuro-oncology: advances and challenges in brain tumor diagnosis, prognosis, and precision treatment
Evidence Blueprint
Mouse models of pediatric high-grade gliomas with MYCN amplification reveal intratumoral heterogeneity and lineage signatures
![](https://psychiatryai.com/wp-content/uploads/2023/04/psychiatryai_com.webp)
☊ AI-Driven Related Evidence Nodes
(recent articles with at least 5 words in title)
More Evidence
![](https://psychiatryai.com/wp-content/uploads/2023/04/psychiatryai_com.webp)
Mouse models of pediatric high-grade gliomas with MYCN amplification reveal intratumoral heterogeneity and lineage signatures
🌐 365 Days
AI Virtual Reality Related Evidence Matrix
The tumor suppressor CREBBP and the oncogene MYCN cooperate to induce malignant brain tumors in mice Refinement of diagnostic criteria for pediatric-type diffuse high-grade glioma, IDH- and H3-wildtype, MYCN-subtype including histopathology, TP53, MYCN and ID2 status Defining the landscape of circular RNAs in neuroblastoma unveils a global suppressive function of MYCN Ependymomas of the spinal region in adults: Clinical and pathological features and MYCN expression levels in spinal ependymomas and myxopapillary ependymomas ROS1 alterations as a potential driver of gliomas in infant, pediatric, and adult patients A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations Integrated molecular and multiparametric MRI mapping of high-grade glioma identifies regional biologic signatures A Novel Type of IDH Wild-type Glioma Characterized by Gliomatosis Cerebri-like Growth Pattern, TERT Promoter Mutation, and Distinct Epigenetic Profile hGFAP-mediated GLI2 overexpression leads to early death and severe cerebellar malformations with rare tumor formation Molecular characteristics and improved survival prediction in a cohort of 2023 ependymomas Pediatric brain tumors Developmental basis of SHH medulloblastoma heterogeneity The 2021 WHO Classification for Gliomas and Implications on Imaging Diagnosis: Part 3-Summary of Imaging Findings on Glioneuronal and Neuronal Tumors MAPK inhibitor sensitivity scores predict sensitivity driven by the immune infiltration in pediatric low-grade gliomas Stem cell modeling of nervous system tumors A prognostic neural epigenetic signature in high-grade glioma Radiogenomics Provides Insights into Gliomas Demonstrating Single-Arm 1p or 19q Deletion Genetics in ophthalmology: molecular blueprints of retinoblastoma Malignant glioma in L-2-Hydroxyglutaric Aciduria: thorough molecular characterization of a case and literature review Concurrent gliomas in patients with multiple sclerosis Gliomatosis cerebri in children: A poor prognostic phenotype of diffuse gliomas with a distinct molecular profile Recurrent atypical teratoid/rhabdoid tumors (AT/RT) reveal discrete features of progression on histology, epigenetics, copy number profiling, and transcriptomics Clinically relevant molecular hallmarks of PFA ependymomas display intratumoral heterogeneity and correlate with tumor morphology Utility of combining OLIG2 and SOX10 IHC expression in CNS tumours: promising biomarkers for subtyping paediatric- and adult-type gliomas Imaging and multi-omics datasets converge to define different neural progenitor origins for ATRT-SHH subgroups A comprehensive genomic study of 390 H3F3A-mutant pediatric and adult diffuse high-grade gliomas, CNS WHO grade 4 Prognostic and predictive biomarkers in central nervous system tumours: the molecular state of play Glioma Haploinsufficiency of NFKBIA reshapes the epigenome antipodal to the IDH mutation and imparts disease fate in diffuse gliomas Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype: case series of a new entity Sequencing of cerebrospinal fluid cell-free DNA facilitated early differential diagnosis of intramedullary spinal cord tumors Refinement of prognostication for IDH-mutant astrocytomas using DNA methylation-based classification "De novo replication repair deficient glioblastoma, IDH-wildtype" is a distinct glioblastoma subtype in adults that may benefit from immune checkpoint blockade pH-responsive targeted nanoparticles release ERK-inhibitor in the hypoxic zone and sensitize free gemcitabine in mutant K-Ras-addicted pancreatic cancer cells and mouse model Rare germline variants in POLE and POLD1 encoding the catalytic subunits of DNA polymerases ε and δ in glioma families Theranostics in Neurooncology: Heading Toward New Horizons Mapping pediatric brain tumors to their origins in the developing cerebellum Reference on copy number variations in pleomorphic xanthoastrocytoma: Implications for diagnostic approach Deciphering early human pancreas development at the single-cell level Compromised transcription-mRNA export factor THOC2 causes R-loop accumulation, DNA damage and adverse neurodevelopment Compromised transcription-mRNA export factor THOC2 causes R-loop accumulation, DNA damage and adverse neurodevelopment Integrated molecular analysis reveals hypermethylation and overexpression of HOX genes to be poor prognosticators in IDH mutant glioma Single-cell transcriptomic sequencing identifies subcutaneous patient-derived xenograft recapitulated medulloblastoma D-2-hydroxyglutarate regulates human brain vascular endothelial cell proliferation and barrier function Systematic analysis of RNA-binding proteins identifies targetable therapeutic vulnerabilities in osteosarcoma Patient- and xenograft-derived organoids recapitulate pediatric brain tumor features and patient treatments Single-cell mapping identifies MSI+ cells as a common origin for diverse subtypes of pancreatic cancer Pediatric CNS tumors and 2021 WHO classification: what do oncologists need from pathologists? Hemangioblastomas and Other Vascular Origating Tumors of Brain or Spinal Cord Semaglutide reduces tumor burden in the GAN diet-induced obese and biopsy-confirmed mouse model of NASH-HCC with advanced fibrosis Transcriptomic and epigenetic dissection of spinal ependymoma (SP-EPN) identifies clinically relevant subtypes enriched for tumors with and without NF2 mutation Proteomic Analysis of Spatial Heterogeneity Identifies HMGB2 as Putative Biomarker of Tumor Progression in Adult-Type Diffuse Astrocytomas Neuropathology of pediatric brain tumors : Implications of the 5th edition of the WHO classification of central nervous system tumors Unclassifiable CNS tumors in DNA methylation-based classification: clinical challenges and prognostic impact A comprehensive analysis of infantile central nervous system tumors to improve distinctive criteria for infant-type hemispheric glioma versus desmoplastic infantile ganglioglioma/astrocytoma Native-state proteomics of Parvalbumin interneurons identifies unique molecular signatures and vulnerabilities to early Alzheimer's pathology Isocitrate Dehydrogenase 1/2 Wildtype Adult Astrocytoma with WHO Grade 2/3 Histological Features: Molecular Re-Classification, Prognostic Factors, Clinical Outcomes Cytotoxic necrotizing factor 1 hinders colon tumorigenesis induced by colibactin-producing Escherichia coli in ApcMin/+ mice Transcriptional features of low-grade neuroepithelial tumors with the BRAF V600E mutation associated with epileptogenicity Establishment and validation of preclinical models of SMARCA4-inactivated and ARID1A/ARID1B co-inactivated dedifferentiated endometrial carcinoma Pituitary neuroendocrine tumors with PIT1/SF1 co-expression show distinct clinicopathological and molecular features Schizophrenia-associated NRXN1 deletions induce developmental-timing- and cell-type-specific vulnerabilities in human brain organoids Schizophrenia-associated NRXN1 deletions induce developmental-timing- and cell-type-specific vulnerabilities in human brain organoids Childhood cancer mutagenesis caused by transposase-derived PGBD5