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5
Pathophys.
2
Histopath.
1
Phenotypes
9
Pathograph
1
Genes
3
Treatments
1
Trials
1
Deep Research

Pathophysiology

5
Cortical Glioneuronal Tumor Formation
DNET forms as a benign cortical glioneuronal tumor with neuronal and glial components, often involving temporal or frontal cortex and producing an epilepsy-associated lesion rather than a high-grade infiltrative glioma.
neuron link astrocytic glial component link oligodendrocyte-like glial component link
low-grade tumor cell proliferation link ↑ INCREASED
cerebral cortex link temporal lobe link
Show evidence (1 reference)
PMID:37525202 SUPPORT Human Clinical
"RESULTS: Fourteen cases were reported. There were 12 males and 2 females. Age range was 9-45 years (mean 19 years). Majority were located in the temporal and frontal lobes."
This human case series supports the young age distribution and cortical temporal/frontal location used for the tumor-formation node.
FGFR1-Driven RAS-MAPK Activation
Specific DNETs are enriched for somatic FGFR1 alterations, including hotspot mutations, tyrosine kinase-domain duplications, and rare fusions/breakpoints. These events converge on RAS-MAPK signaling and provide the central molecular mechanism for many neuropathology-confirmed tumors.
FGFR1 link
MAPK cascade link ↑ INCREASED
Show evidence (2 references)
PMID:26920151 SUPPORT Human Clinical
"In 43 sporadic cases, in which the diagnosis of DNET could be confirmed on central blinded neuropathology review, FGFR1 alterations were also frequent and mainly comprised intragenic tyrosine kinase FGFR1 duplication and multiple mutants in cis (25/43; 58.1 %) while BRAF p.V600E alterations were..."
The centrally reviewed human tumor cohort supports FGFR1 alteration as the dominant driver event in confirmed DNET.
PMID:26920151 SUPPORT Human Clinical
"In conclusion, constitutional and somatic FGFR1 alterations and MAP kinase pathway activation are key events in the pathogenesis of DNET."
The authors explicitly connect constitutional/somatic FGFR1 abnormalities with MAP kinase activation in DNET pathogenesis.
DNET Spectrum Molecular Heterogeneity
Specific DNET is molecularly more homogeneous than historical non-specific or diffuse DNT diagnoses. Broader DNET/MNGT/PLNTY-spectrum tumors can harbor BRAF, FGFR1, NF1, PDGFRA, FGFR2, NTRK2, and other alterations that converge on MAPK and PI3K/mTOR signaling, so molecular diagnosis helps separate true DNET from overlapping low-grade neuroepithelial entities.
FGFR1 link
MAPK cascade link ⚠ ABNORMAL
Show evidence (2 references)
PMID:35836307 SUPPORT Human Clinical
"Specific DNT is a homogeneous group of tumours sharing characteristics of paediatric low-grade gliomas: a quiet genome with a recurrent genomic alteration in the RAS-MAPK signalling pathway, a distinct DNA methylation profile and a good prognosis but showing progression in some cases."
This integrative human tumor cohort supports separating specific DNT from heterogeneous non-specific/diffuse tumors and anchors the RAS-MAPK mechanism.
PMID:31617914 SUPPORT Human Clinical
"Overall, DNT-MNGT spectrum tumors exhibit diverse genomic alterations, with more than half (19/33) leading to MAPK/PI3K pathway alterations."
This human genomic series supports modeling broader DNT-spectrum molecular heterogeneity as a MAPK/PI3K-pathway convergent pattern.
Tumor-Associated Cortical Hyperexcitability
DNET is an epileptogenic cortical tumor. Seizures arise when the glioneuronal lesion involves cortical neurons and related networks; peritumoral epileptogenic zones and associated focal cortical dysplasia can contribute to drug-resistant focal epilepsy.
cortical neuron link
cerebral cortex link
Show evidence (1 reference)
PMID:36699536 SUPPORT Other
"Brain tumors can always result in seizures when involving the cortical neurons or their circuits, and they were found to be one of the most common etiologies of intractable focal seizures."
This review supports the cortical-neuron circuit mechanism linking DNET/LEAT location to intractable focal seizures.
Adjacent Focal Cortical Dysplasia
Some DNETs show adjacent cortical dysplasia, representing dual pathology that can contribute to the epileptogenic peritumoral cortex and surgical planning.
cerebral cortex link
Show evidence (1 reference)
PMID:37525202 SUPPORT Human Clinical
"Cortical dysplasia was noted in adjacent glial tissue in four cases."
This case series directly supports adjacent cortical dysplasia as a DNET dual-pathology finding.

Histopathology

2
Specific Glioneuronal Element
The diagnostic hallmark is the specific glioneuronal element, with columns of oligodendrocyte-like cells and floating neurons in a mucinous matrix.
Show evidence (1 reference)
PMID:26920151 SUPPORT Human Clinical
"The histopathological hallmark of DNET is the specific glioneuronal element, i.e. the presence of columns of oligodendroglial-like cells and so-called floating neurons [6]."
This supports the specific glioneuronal element as the diagnostic histologic hallmark.
Multinodular Pattern
Classic DNETs show a multinodular pattern with low proliferative activity and no high-grade features such as necrosis or significant mitotic activity.
Show evidence (1 reference)
PMID:37525202 SUPPORT Human Clinical
"Histologically, all cases demonstrated a multinodular pattern, specific glioneuronal component, and floating neurons."
This human case series supports multinodular architecture and floating neurons as common DNET histopathologic findings.

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Dysembryoplastic Neuroepithelial Tumor Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.

Phenotypes

1
Focal-Onset Seizures Neurological HP:0007359
Show evidence (2 references)
PMID:37525202 SUPPORT Human Clinical
"BACKGROUND: Dysembryoplastic neuroepithelial tumors are rare benign supratentotrial epilepsy-associated glioneuronal tumors of children and young adults. Patients have a long history of seizures."
The case-series abstract directly supports seizures as the major presentation.
PMID:26920151 SUPPORT Human Clinical
"Dysembryoplastic neuroepithelial tumor (DNET) is a benign brain tumor associated with intractable drug-resistant epilepsy."
This tumor genetics paper confirms the association with intractable, drug-resistant epilepsy.
🧬

Genetic Associations

1
FGFR1 (Common somatic driver, with rare familial germline predisposition reported.)
Show evidence (3 references)
PMID:26920151 SUPPORT Human Clinical
"By whole-exome sequencing of the familial cases, we identified a novel germline FGFR1 mutation, p.R661P."
This supports rare germline FGFR1 predisposition in familial DNET.
PMID:26920151 SUPPORT Human Clinical
"Somatic activating FGFR1 mutations (p.N546K or p.K656E) were observed in the tumor samples"
This supports somatic activating FGFR1 mutations in tumor tissue.
PMID:26920151 SUPPORT Computational
"further evidence for functional relevance was obtained by in silico modeling."
This separately classifies the in silico modeling component of the FGFR1 functional evidence.
💊

Treatments

3
Surgical Resection
Action: surgical resection MAXO:0000448
Maximal safe resection or lesionectomy is the main disease-directed therapy, aiming for tumor control and seizure freedom. Shorter epilepsy duration and gross total removal predict better seizure outcomes.
Mechanism Target:
MODULATES Cortical Glioneuronal Tumor Formation — Resection removes the glioneuronal tumor and associated epileptogenic lesion.
INHIBITS Tumor-Associated Cortical Hyperexcitability — Resection reduces seizure-generating cortical tumor tissue.
Target Phenotypes: Focal-onset seizure
Show evidence (3 references)
PMID:36672006 SUPPORT Human Clinical
"At the final follow-up, 49 patients (77.8%) were seizure-free."
This supports favorable seizure outcomes after surgery in a human DNT cohort.
PMID:36672006 SUPPORT Human Clinical
"Gross total removal of the tumor and a short epilepsy duration were significant predictors of seizure freedom."
This supports gross total tumor removal as an important treatment goal.
PMID:26514362 SUPPORT Human Clinical
"The median seizure freedom rate was 86% (interquartile range 77-93%) with only one study reporting fewer than 60% of patients seizure free."
This systematic review supports high seizure-freedom rates after DNET resection.
Anti-Seizure Medication
Action: Pharmacotherapy NCIT:C15986
Agent: anticonvulsant
Anti-seizure medications are used to manage DNET-associated epilepsy, although seizures are often drug-resistant before definitive surgical management.
Target Phenotypes: Focal-onset seizure
Show evidence (1 reference)
PMID:26514362 SUPPORT Human Clinical
"The number of seizure-free patients who discontinued anti-epileptic drugs varied widely from zero to all patients."
This supports anti-epileptic drug use as part of clinical management in surgical DNET epilepsy series.
Mirdametinib MEK Inhibition Trial Therapy
Action: Pharmacotherapy NCIT:C15986
Agent: mirdametinib
Mirdametinib is an investigational brain-penetrant MEK1/2 inhibitor being evaluated in the SJ901 pediatric/AYA low-grade glioma trial; for DNET, this is mechanistically relevant to FGFR1-driven RAS-MAPK activation but remains investigational rather than established standard care.
Mechanism Target:
INHIBITS FGFR1-Driven RAS-MAPK Activation — MEK inhibition targets downstream MAPK pathway signaling activated by FGFR1 alterations.
Show evidence (1 reference)
clinicaltrials:NCT04923126 PARTIAL Human Clinical
"This is an open-label, multi-center, Phase 1/2 study of the brain-penetrant MEK inhibitor, mirdametinib (PD-0325901), in patients with pediatric low-grade glioma (pLGG)."
The trial record supports an investigational MEK-inhibitor therapy for pediatric low-grade glioma; DNET relevance is mechanistic and trial-eligibility based as surfaced by Falcon, so support is marked partial.
🔬

Clinical Trials

1
NCT04923126 PHASE_I RECRUITING
SJ901 is an open-label multicenter Phase 1/2 study of mirdametinib, a brain-penetrant MEK1/2 inhibitor, in pediatric low-grade glioma. Falcon identified DNET as an eligible LEAT histology in this MAPK-pathway trial.
Show evidence (1 reference)
clinicaltrials:NCT04923126 SUPPORT Human Clinical
"This is an open-label, multi-center, Phase 1/2 study of the brain-penetrant MEK inhibitor, mirdametinib (PD-0325901), in patients with pediatric low-grade glioma (pLGG)."
This exact trial-cache quote supports adding SJ901 as a relevant low-grade-glioma MEK-inhibitor clinical trial.
{ }

Source YAML

click to show
name: Dysembryoplastic Neuroepithelial Tumor
creation_date: "2026-05-11T14:55:21Z"
updated_date: "2026-05-11T14:55:21Z"
description: >-
  Dysembryoplastic neuroepithelial tumor (DNET/DNT) is a rare WHO grade 1
  glioneuronal brain neoplasm and a prototypic low-grade epilepsy-associated
  neuroepithelial tumor. It typically arises in cortical supratentorial brain,
  especially temporal and frontal lobes, in children, adolescents, and young
  adults with long-standing focal seizures. Integrated diagnosis combines
  clinical epilepsy history, MRI, neuropathology with a specific glioneuronal
  element, and increasingly molecular testing for FGFR1/RAS-MAPK alterations.
categories:
- Central Nervous System Neoplasm
- Mixed Neuronal-Glial Tumor
- Epilepsy-Associated Tumor
- Pediatric Brain Tumor
- Low-Grade Glioma
parents:
- mixed neuronal-glial tumor
- brain neoplasm
- structural epilepsy
disease_term:
  preferred_term: dysembryoplastic neuroepithelial tumor
  term:
    id: MONDO:0005505
    label: dysembryoplastic neuroepithelial tumor
pathophysiology:
- name: Cortical Glioneuronal Tumor Formation
  description: >-
    DNET forms as a benign cortical glioneuronal tumor with neuronal and glial
    components, often involving temporal or frontal cortex and producing an
    epilepsy-associated lesion rather than a high-grade infiltrative glioma.
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  - preferred_term: astrocytic glial component
    term:
      id: CL:0000127
      label: astrocyte
  - preferred_term: oligodendrocyte-like glial component
    term:
      id: CL:0000128
      label: oligodendrocyte
  locations:
  - preferred_term: cerebral cortex
    term:
      id: UBERON:0000956
      label: cerebral cortex
  - preferred_term: temporal lobe
    term:
      id: UBERON:0001871
      label: temporal lobe
  biological_processes:
  - preferred_term: low-grade tumor cell proliferation
    modifier: INCREASED
    term:
      id: GO:0008283
      label: cell population proliferation
  evidence:
  - reference: PMID:37525202
    reference_title: "Clinicopathological features of dysembryoplastic neuroepithelial tumor: a case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      RESULTS: Fourteen cases were reported. There were 12 males and 2 females. Age
      range was 9-45 years (mean 19 years). Majority were located in the temporal and
      frontal lobes.
    explanation: >-
      This human case series supports the young age distribution and cortical
      temporal/frontal location used for the tumor-formation node.
  downstream:
  - target: FGFR1-Driven RAS-MAPK Activation
    description: Many confirmed DNETs carry FGFR1 alterations that activate MAPK signaling.
  - target: Tumor-Associated Cortical Hyperexcitability
    description: The cortical glioneuronal lesion is the structural substrate for focal seizures.
- name: FGFR1-Driven RAS-MAPK Activation
  description: >-
    Specific DNETs are enriched for somatic FGFR1 alterations, including hotspot
    mutations, tyrosine kinase-domain duplications, and rare fusions/breakpoints.
    These events converge on RAS-MAPK signaling and provide the central molecular
    mechanism for many neuropathology-confirmed tumors.
  genes:
  - preferred_term: FGFR1
    term:
      id: hgnc:3688
      label: FGFR1
  gene_products:
  - preferred_term: fibroblast growth factor receptor 1
    term:
      id: NCIT:C17590
      label: Fibroblast Growth Factor Receptor 1
  biological_processes:
  - preferred_term: MAPK cascade
    modifier: INCREASED
    term:
      id: GO:0000165
      label: MAPK cascade
  evidence:
  - reference: PMID:26920151
    reference_title: "Germline and somatic FGFR1 abnormalities in dysembryoplastic neuroepithelial tumors."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In 43 sporadic cases, in which the diagnosis of DNET could be confirmed on
      central blinded neuropathology review, FGFR1 alterations were also frequent
      and mainly comprised intragenic tyrosine kinase FGFR1 duplication and multiple
      mutants in cis (25/43; 58.1 %) while BRAF p.V600E alterations were absent (0/43).
    explanation: >-
      The centrally reviewed human tumor cohort supports FGFR1 alteration as the
      dominant driver event in confirmed DNET.
  - reference: PMID:26920151
    reference_title: "Germline and somatic FGFR1 abnormalities in dysembryoplastic neuroepithelial tumors."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In conclusion, constitutional and somatic FGFR1 alterations and MAP kinase
      pathway activation are key events in the pathogenesis of DNET.
    explanation: >-
      The authors explicitly connect constitutional/somatic FGFR1 abnormalities
      with MAP kinase activation in DNET pathogenesis.
  downstream:
  - target: Tumor-Associated Cortical Hyperexcitability
    description: MAPK-driven glioneuronal tumor formation creates an epileptogenic cortical lesion.
- name: DNET Spectrum Molecular Heterogeneity
  description: >-
    Specific DNET is molecularly more homogeneous than historical non-specific or
    diffuse DNT diagnoses. Broader DNET/MNGT/PLNTY-spectrum tumors can harbor
    BRAF, FGFR1, NF1, PDGFRA, FGFR2, NTRK2, and other alterations that converge on
    MAPK and PI3K/mTOR signaling, so molecular diagnosis helps separate true DNET
    from overlapping low-grade neuroepithelial entities.
  genes:
  - preferred_term: FGFR1
    term:
      id: hgnc:3688
      label: FGFR1
  biological_processes:
  - preferred_term: MAPK cascade
    modifier: ABNORMAL
    term:
      id: GO:0000165
      label: MAPK cascade
  evidence:
  - reference: PMID:35836307
    reference_title: "The genomic landscape of dysembryoplastic neuroepithelial tumours and a comprehensive analysis of recurrent cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Specific DNT is a homogeneous group of tumours sharing characteristics of
      paediatric low-grade gliomas: a quiet genome with a recurrent genomic alteration
      in the RAS-MAPK signalling pathway, a distinct DNA methylation profile and a
      good prognosis but showing progression in some cases.
    explanation: >-
      This integrative human tumor cohort supports separating specific DNT from
      heterogeneous non-specific/diffuse tumors and anchors the RAS-MAPK mechanism.
  - reference: PMID:31617914
    reference_title: Genomic Analysis of Dysembryoplastic Neuroepithelial Tumor Spectrum Reveals a Diversity of Molecular Alterations Dysregulating the MAPK and PI3K/mTOR Pathways.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Overall, DNT-MNGT spectrum tumors exhibit diverse genomic alterations, with
      more than half (19/33) leading to MAPK/PI3K pathway alterations.
    explanation: >-
      This human genomic series supports modeling broader DNT-spectrum molecular
      heterogeneity as a MAPK/PI3K-pathway convergent pattern.
- name: Tumor-Associated Cortical Hyperexcitability
  description: >-
    DNET is an epileptogenic cortical tumor. Seizures arise when the glioneuronal
    lesion involves cortical neurons and related networks; peritumoral epileptogenic
    zones and associated focal cortical dysplasia can contribute to drug-resistant
    focal epilepsy.
  cell_types:
  - preferred_term: cortical neuron
    term:
      id: CL:0000540
      label: neuron
  locations:
  - preferred_term: cerebral cortex
    term:
      id: UBERON:0000956
      label: cerebral cortex
  evidence:
  - reference: PMID:36699536
    reference_title: "Low-grade epilepsy-associated neuroepithelial tumors: Tumor spectrum and diagnosis based on genetic alterations."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Brain tumors can always result in seizures when involving the cortical neurons
      or their circuits, and they were found to be one of the most common etiologies
      of intractable focal seizures.
    explanation: >-
      This review supports the cortical-neuron circuit mechanism linking DNET/LEAT
      location to intractable focal seizures.
- name: Adjacent Focal Cortical Dysplasia
  description: >-
    Some DNETs show adjacent cortical dysplasia, representing dual pathology that
    can contribute to the epileptogenic peritumoral cortex and surgical planning.
  locations:
  - preferred_term: cerebral cortex
    term:
      id: UBERON:0000956
      label: cerebral cortex
  evidence:
  - reference: PMID:37525202
    reference_title: "Clinicopathological features of dysembryoplastic neuroepithelial tumor: a case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Cortical dysplasia was noted in adjacent glial tissue in four cases.
    explanation: >-
      This case series directly supports adjacent cortical dysplasia as a DNET
      dual-pathology finding.
phenotypes:
- category: Neurological
  name: Focal-Onset Seizures
  description: >-
    Long-standing focal seizures are the hallmark clinical presentation and may be
    drug-resistant before surgery.
  phenotype_term:
    preferred_term: Focal-onset seizure
    term:
      id: HP:0007359
      label: Focal-onset seizure
  evidence:
  - reference: PMID:37525202
    reference_title: "Clinicopathological features of dysembryoplastic neuroepithelial tumor: a case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      BACKGROUND: Dysembryoplastic neuroepithelial tumors are rare benign
      supratentotrial epilepsy-associated glioneuronal tumors of children and young
      adults. Patients have a long history of seizures.
    explanation: >-
      The case-series abstract directly supports seizures as the major presentation.
  - reference: PMID:26920151
    reference_title: "Germline and somatic FGFR1 abnormalities in dysembryoplastic neuroepithelial tumors."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Dysembryoplastic neuroepithelial tumor (DNET) is a benign brain tumor
      associated with intractable drug-resistant epilepsy.
    explanation: >-
      This tumor genetics paper confirms the association with intractable,
      drug-resistant epilepsy.
histopathology:
- name: Specific Glioneuronal Element
  description: >-
    The diagnostic hallmark is the specific glioneuronal element, with columns of
    oligodendrocyte-like cells and floating neurons in a mucinous matrix.
  diagnostic: true
  evidence:
  - reference: PMID:26920151
    reference_title: "Germline and somatic FGFR1 abnormalities in dysembryoplastic neuroepithelial tumors."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The histopathological hallmark of DNET is the specific glioneuronal element,
      i.e. the presence of columns of oligodendroglial-like cells and so-called
      floating neurons [6].
    explanation: >-
      This supports the specific glioneuronal element as the diagnostic histologic
      hallmark.
- name: Multinodular Pattern
  description: >-
    Classic DNETs show a multinodular pattern with low proliferative activity and
    no high-grade features such as necrosis or significant mitotic activity.
  finding_term:
    preferred_term: nodular pattern
    term:
      id: NCIT:C35899
      label: Nodular Pattern
  evidence:
  - reference: PMID:37525202
    reference_title: "Clinicopathological features of dysembryoplastic neuroepithelial tumor: a case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Histologically, all cases demonstrated a multinodular pattern, specific
      glioneuronal component, and floating neurons.
    explanation: >-
      This human case series supports multinodular architecture and floating
      neurons as common DNET histopathologic findings.
diagnosis:
- name: Brain MRI
  description: >-
    MRI is central to preoperative evaluation and can identify cortical lesion
    patterns that support DNET/LEAT diagnosis and surgical planning.
  diagnosis_term:
    preferred_term: magnetic resonance imaging procedure
    term:
      id: MAXO:0000424
      label: magnetic resonance imaging procedure
  results: Cortical tumor location and MRI pattern guide differential diagnosis and surgical planning.
  evidence:
  - reference: PMID:36672006
    reference_title: Long-Term Seizure Outcomes and Predictors in Patients with Dysembryoplastic Neuroepithelial Tumors Associated with Epilepsy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Younger age of seizure onset, bilateral interictal epileptiform discharges,
      and MRI type 3 tumors were risk factors for poor prognosis;
    explanation: >-
      This clinical surgical cohort supports MRI pattern as clinically relevant in
      DNET epilepsy prognosis.
- name: Electroencephalography
  description: >-
    EEG helps localize epileptiform activity and risk-stratify seizure outcomes in
    DNET-associated epilepsy.
  diagnosis_term:
    preferred_term: electroencephalography
    term:
      id: MAXO:0000932
      label: electroencephalography
  results: Interictal epileptiform discharges inform localization and outcome prediction.
  evidence:
  - reference: PMID:36672006
    reference_title: Long-Term Seizure Outcomes and Predictors in Patients with Dysembryoplastic Neuroepithelial Tumors Associated with Epilepsy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Younger age of seizure onset, bilateral interictal epileptiform discharges,
      and MRI type 3 tumors were risk factors for poor prognosis;
    explanation: >-
      This supports interictal EEG findings as clinically meaningful in
      DNET-associated epilepsy.
- name: Molecular Testing for FGFR1 and MAPK Pathway Alterations
  description: >-
    Targeted sequencing, fusion testing, and methylation profiling can support
    difficult DNET diagnoses and distinguish specific DNT from overlapping
    low-grade neuroepithelial tumor entities.
  diagnosis_term:
    preferred_term: genetic testing
    term:
      id: MAXO:0000127
      label: genetic testing
  results: FGFR1 alteration, RAS-MAPK pathway event, or DNT methylation class supports integrated diagnosis.
  evidence:
  - reference: PMID:26920151
    reference_title: "Germline and somatic FGFR1 abnormalities in dysembryoplastic neuroepithelial tumors."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Here, targeted analysis for FGFR1 hotspot mutations may provide a first step
      to aid the diagnosis of DNET and could be supplemented by analyses for FGFR1
      fusion transcripts and FGFR1-TKD.
    explanation: >-
      This supports FGFR1 mutation/fusion/tyrosine-kinase-duplication testing as a
      diagnostic adjunct.
- name: DNA Methylation Profiling
  description: >-
    DNA methylation profiling can help distinguish specific DNT from heterogeneous
    non-specific/diffuse DNT-like diagnoses and other low-grade neuroepithelial
    tumors.
  diagnosis_term:
    preferred_term: DNA methylation profiling
  results: A distinct DNA methylation profile supports integrated DNT classification.
  evidence:
  - reference: PMID:35836307
    reference_title: "The genomic landscape of dysembryoplastic neuroepithelial tumours and a comprehensive analysis of recurrent cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      METHODS: We used targeted methods (immunohistochemistry, fluorescence in situ
      hybridisation and targeted sequencing) and large-scale genomic methodologies
      including DNA methylation profiling to perform an integrative analysis to better
      characterise a large retrospective cohort of 82 DNTs, enriched for tumours that
      showed progression on imaging.
    explanation: >-
      This supports DNA methylation profiling as part of integrative diagnostic
      characterization for DNT.
genetic:
- name: FGFR1
  gene_term:
    preferred_term: FGFR1
    term:
      id: hgnc:3688
      label: FGFR1
  association: Common somatic driver, with rare familial germline predisposition reported.
  relationship_type: CAUSATIVE
  variant_origin: GERMLINE_AND_SOMATIC
  evidence:
  - reference: PMID:26920151
    reference_title: "Germline and somatic FGFR1 abnormalities in dysembryoplastic neuroepithelial tumors."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      By whole-exome sequencing of the familial cases, we identified a novel
      germline FGFR1 mutation, p.R661P.
    explanation: >-
      This supports rare germline FGFR1 predisposition in familial DNET.
  - reference: PMID:26920151
    reference_title: "Germline and somatic FGFR1 abnormalities in dysembryoplastic neuroepithelial tumors."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Somatic activating FGFR1 mutations (p.N546K or p.K656E) were observed in the
      tumor samples
    explanation: >-
      This supports somatic activating FGFR1 mutations in tumor tissue.
  - reference: PMID:26920151
    reference_title: "Germline and somatic FGFR1 abnormalities in dysembryoplastic neuroepithelial tumors."
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: >-
      further evidence for functional relevance was obtained by in silico modeling.
    explanation: >-
      This separately classifies the in silico modeling component of the FGFR1
      functional evidence.
treatments:
- name: Surgical Resection
  description: >-
    Maximal safe resection or lesionectomy is the main disease-directed therapy,
    aiming for tumor control and seizure freedom. Shorter epilepsy duration and
    gross total removal predict better seizure outcomes.
  treatment_term:
    preferred_term: surgical resection
    term:
      id: MAXO:0000448
      label: surgical resection
  target_phenotypes:
  - preferred_term: Focal-onset seizure
    term:
      id: HP:0007359
      label: Focal-onset seizure
  target_mechanisms:
  - target: Cortical Glioneuronal Tumor Formation
    treatment_effect: MODULATES
    description: Resection removes the glioneuronal tumor and associated epileptogenic lesion.
  - target: Tumor-Associated Cortical Hyperexcitability
    treatment_effect: INHIBITS
    description: Resection reduces seizure-generating cortical tumor tissue.
  evidence:
  - reference: PMID:36672006
    reference_title: Long-Term Seizure Outcomes and Predictors in Patients with Dysembryoplastic Neuroepithelial Tumors Associated with Epilepsy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      At the final follow-up, 49 patients (77.8%) were seizure-free.
    explanation: >-
      This supports favorable seizure outcomes after surgery in a human DNT cohort.
  - reference: PMID:36672006
    reference_title: Long-Term Seizure Outcomes and Predictors in Patients with Dysembryoplastic Neuroepithelial Tumors Associated with Epilepsy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Gross total removal of the tumor and a short epilepsy duration were significant
      predictors of seizure freedom.
    explanation: >-
      This supports gross total tumor removal as an important treatment goal.
  - reference: PMID:26514362
    reference_title: Review of seizure outcomes after surgical resection of dysembryoplastic neuroepithelial tumors.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The median seizure freedom rate was 86% (interquartile range 77-93%) with
      only one study reporting fewer than 60% of patients seizure free.
    explanation: >-
      This systematic review supports high seizure-freedom rates after DNET resection.
- name: Anti-Seizure Medication
  description: >-
    Anti-seizure medications are used to manage DNET-associated epilepsy, although
    seizures are often drug-resistant before definitive surgical management.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: anticonvulsant
      term:
        id: NCIT:C264
        label: Anticonvulsant Agent
  target_phenotypes:
  - preferred_term: Focal-onset seizure
    term:
      id: HP:0007359
      label: Focal-onset seizure
  evidence:
  - reference: PMID:26514362
    reference_title: Review of seizure outcomes after surgical resection of dysembryoplastic neuroepithelial tumors.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The number of seizure-free patients who discontinued anti-epileptic drugs
      varied widely from zero to all patients.
    explanation: >-
      This supports anti-epileptic drug use as part of clinical management in
      surgical DNET epilepsy series.
- name: Mirdametinib MEK Inhibition Trial Therapy
  description: >-
    Mirdametinib is an investigational brain-penetrant MEK1/2 inhibitor being
    evaluated in the SJ901 pediatric/AYA low-grade glioma trial; for DNET, this
    is mechanistically relevant to FGFR1-driven RAS-MAPK activation but remains
    investigational rather than established standard care.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: mirdametinib
  target_mechanisms:
  - target: FGFR1-Driven RAS-MAPK Activation
    treatment_effect: INHIBITS
    description: MEK inhibition targets downstream MAPK pathway signaling activated by FGFR1 alterations.
  evidence:
  - reference: clinicaltrials:NCT04923126
    reference_title: "SJ901: Phase 1/2 Evaluation of Single Agent Mirdametinib (PD-0325901), a Brain-Penetrant MEK1/2 Inhibitor, for the Treatment of Children, Adolescents, and Young Adults With Low-Grade Glioma"
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This is an open-label, multi-center, Phase 1/2 study of the brain-penetrant
      MEK inhibitor, mirdametinib (PD-0325901), in patients with pediatric low-grade
      glioma (pLGG).
    explanation: >-
      The trial record supports an investigational MEK-inhibitor therapy for
      pediatric low-grade glioma; DNET relevance is mechanistic and trial-eligibility
      based as surfaced by Falcon, so support is marked partial.
clinical_trials:
- name: NCT04923126
  phase: PHASE_I
  status: RECRUITING
  description: >-
    SJ901 is an open-label multicenter Phase 1/2 study of mirdametinib, a
    brain-penetrant MEK1/2 inhibitor, in pediatric low-grade glioma. Falcon
    identified DNET as an eligible LEAT histology in this MAPK-pathway trial.
  evidence:
  - reference: clinicaltrials:NCT04923126
    reference_title: "SJ901: Phase 1/2 Evaluation of Single Agent Mirdametinib (PD-0325901), a Brain-Penetrant MEK1/2 Inhibitor, for the Treatment of Children, Adolescents, and Young Adults With Low-Grade Glioma"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This is an open-label, multi-center, Phase 1/2 study of the brain-penetrant
      MEK inhibitor, mirdametinib (PD-0325901), in patients with pediatric low-grade
      glioma (pLGG).
    explanation: >-
      This exact trial-cache quote supports adding SJ901 as a relevant
      low-grade-glioma MEK-inhibitor clinical trial.
  notes: >-
    ClinicalTrials.gov lists this as a combined Phase 1/2 study; mapped to
    PHASE_I because the schema accepts a single phase value. ClinicalTrials.gov
    API status checked on 2026-05-11 reported RECRUITING. The corresponding
    treatment entry links mirdametinib to FGFR1-Driven RAS-MAPK Activation via
    target_mechanisms, because the ClinicalTrial schema does not currently allow
    target_mechanisms directly.
datasets:
📚

References & Deep Research

Deep Research

1
Falcon
Dysembryoplastic Neuroepithelial Tumor (DNET/DNT): Disease Characteristics Research Report
Edison Scientific Literature 45 citations 2026-05-11T11:29:46.550060

Dysembryoplastic Neuroepithelial Tumor (DNET/DNT): Disease Characteristics Research Report

Target disease: Dysembryoplastic neuroepithelial tumor (also written dysembryoplastic neuroepithelial tumour; abbreviation DNET or DNT). (rahim2023clinicopathologicalfeaturesof pages 1-2, khalilov2024atypicalpresentationof pages 1-2)

Category (high level): WHO-defined circumscribed glioneuronal tumor; a prototypic low-grade epilepsy-associated neuroepithelial tumor (LEAT) entity. (xie2023lowgradeepilepsyassociatedneuroepithelial pages 1-2, rosemberg2023longtermepilepsyassociatedtumors pages 1-2)

MONDO ID: Not found in the retrieved primary literature corpus used here (evidence gap noted). (rosemberg2023longtermepilepsyassociatedtumors pages 1-2)

Executive snapshot (knowledge-base compact)

Domain Key characteristics
Definition/classification • Rare benign glioneuronal tumor; classic representative of low-grade epilepsy-associated tumors (LEATs) • WHO CNS 2021/5th-ed context: WHO grade 1 • Often termed DNET/DNT in literature • Characteristic alteration in LEAT classification tables: FGFR1 (xie2023lowgradeepilepsyassociatedneuroepithelial pages 2-3, xie2023lowgradeepilepsyassociatedneuroepithelial pages 1-2, xie2023lowgradeepilepsyassociatedneuroepithelial media 10d99c66)
Epidemiology • Rare: estimated incidence ~0.03/100,000/year in the US • Reported prevalence among CNS tumors: ~1.2% in patients <20 years and ~0.2% in >20 years • DNT/DNET is among the commonest LEATs, with ganglioglioma together accounting for >75% of pediatric LEATs and >80% of LEATs in some epilepsy-surgery series (zhang2022longtermseizureoutcomes pages 1-2, rahim2023clinicopathologicalfeaturesof pages 1-2, pelissier2026pediatriclowgradeepilepsyassociated pages 1-3, iijima2024genotyperelevantneuroimagingfeatures pages 1-2)
Typical presentation • Usually children/adolescents or young adults; LEAT seizure onset often ~12–15 years • Main presentation is chronic focal/drug-resistant epilepsy; seizures may be the only symptom • Rare non-epileptic presentations occur (e.g., headache without epileptiform activity) (xie2023lowgradeepilepsyassociatedneuroepithelial pages 1-2, khalilov2024atypicalpresentationof pages 1-2, rahim2023clinicopathologicalfeaturesof pages 1-2)
Anatomy/location • Supratentorial, cortical or cortico-subcortical tumor • Strong temporal lobe predilection: ~65–80% of LEATs temporal; >67% temporal in DNT series • Frontal lobe is the second most common site • Frequent association with adjacent focal cortical dysplasia/peritumoral cortical dysplasia (xie2023lowgradeepilepsyassociatedneuroepithelial pages 1-2, rahim2023clinicopathologicalfeaturesof pages 1-2, bonney2016reviewofseizure pages 4-5)
Imaging/pathology hallmarks • MRI often shows cortical-based lesion spanning cortical thickness, usually without major mass effect/edema • MRI patterns reported as cystic-like, nodular-like, and dysplastic-like types • Histology: multinodular architecture, specific glioneuronal element, oligodendrocyte-like cells in mucinous matrix, and “floating neurons” • Very low proliferative index; Ki-67 typically <1% (rahim2023clinicopathologicalfeaturesof pages 1-2, zhang2022longtermseizureoutcomes pages 2-5)
Molecular genetics • FGFR1 is the dominant driver: hotspot mutations (p.N546, p.K656), tyrosine kinase domain/internal tandem duplication, and rare fusions • Frequency of FGFR1 alterations reported at ~58.1% in neuropathology-confirmed DNT (25/43) and ~68% in a 58-case specific DNT cohort • MAPK pathway activation is central; some tumors also implicate PI3K/mTOR signaling • BRAF V600E can be reported in the broader DNT spectrum, but was absent in some well-curated specific DNT cohorts; rare alternative fusions include LHFPL3::NTRK2 (rivera2016germlineandsomatic pages 1-2, lucas2020comprehensiveanalysisof pages 1-2, jesus‐ribeiro2022thelandscapeof pages 6-7, pages2022thegenomiclandscape pages 10-10, chen2022casereporta pages 1-2)
Diagnostics/molecular testing • Diagnosis remains integrated: clinical epilepsy history + MRI + neuropathology • Pre-op workup often includes long-term video-EEG; MEG/PET/SEEG used when epileptogenic zone is unclear • Molecular testing increasingly useful for difficult cases: targeted sequencing for FGFR1/BRAF/NTRK alterations and DNA methylation profiling for classification support • sEEG-electrode-derived micro-tissue has been shown feasible for NGS and methylation analysis in a 2024 DNET case (zhang2022longtermseizureoutcomes pages 2-5, gatesman2024characterizationoflow‐grade pages 1-2, xie2023lowgradeepilepsyassociatedneuroepithelial media f56d460d)
Treatment/management • Mainstay is maximal safe surgical resection/lesionectomy, ideally including epileptogenic zone when indicated • Gross-total resection is generally favored for seizure control; lesionectomy alone may suffice in temporal LEATs with normal hippocampus • Anti-seizure medications are used for tumor-related epilepsy, but DNET-associated epilepsy is often pharmacoresistant • Chemo/radiotherapy usually not required for typical indolent DNET; targeted therapy remains investigational/exceptional (takayama2022ishippocampalresection pages 1-2, zhang2022longtermseizureoutcomes pages 1-2, gatesman2024characterizationoflow‐grade pages 1-2)
Outcomes/prognosis • Overall prognosis is favorable; biologically stable tumor with rare malignant transformation • In a 63-patient DNT cohort, 49/63 (77.8%) were seizure-free after surgery; seizure-recurrence-free rates were 82.5% at 2 years, 79.0% at 5 years, and 76.5% at 10 years • Across prior studies, seizure freedom after gross-total resection is often >80%; systematic review median seizure-free range IQR 77–93% • Better outcomes linked to gross-total resection and shorter epilepsy duration; MRI type 3/dysplastic-like pattern and bilateral interictal discharges predict worse seizure outcome (zhang2022longtermseizureoutcomes pages 1-2, zhang2022longtermseizureoutcomes pages 2-5, bonney2016reviewofseizure pages 4-5)
Recent developments 2023-2024 • 2023 LEAT reviews reinforced DNET as a WHO grade 1, FGFR1-linked LEAT entity • 2024 neuroimaging-genotype work showed FGFR1-associated LEAT imaging pattern with 100% sensitivity/specificity in that cohort and poorer seizure-free rates than BRAF-pattern tumors • 2024 S/EEG-based molecular diagnosis showed practical minimally invasive tumor profiling • 2023–2024 literature increasingly emphasizes integrated histology + molecular genetics + methylation classification for diagnostically ambiguous low-grade epilepsy-associated tumors (iijima2024genotyperelevantneuroimagingfeatures pages 1-2, gatesman2024characterizationoflow‐grade pages 1-2, rosemberg2023longtermepilepsyassociatedtumors pages 1-2, rahim2023clinicopathologicalfeaturesof pages 6-7)

Table: This compact table summarizes core disease-characteristic facts for dysembryoplastic neuroepithelial tumor (DNET/DNT), including classification, phenotype, molecular genetics, diagnosis, treatment, and prognosis. It is designed as a concise knowledge-base-ready snapshot with quantitative details and context-ID citations.

1. Disease Information

1.1 What is the disease?

Dysembryoplastic neuroepithelial tumor is a rare, benign/indolent, supratentorial, epilepsy-associated glioneuronal tumor that most commonly affects children and young adults and typically presents with long-standing focal seizures, often drug-resistant. (rahim2023clinicopathologicalfeaturesof pages 1-2, khalilov2024atypicalpresentationof pages 1-2)

Within the LEAT concept (long-term/low-grade epilepsy-associated tumors), DNET is recognized as one of the typical representatives alongside ganglioglioma, with a predilection for neocortical temporal lobe involvement and generally benign growth behavior. (xie2023lowgradeepilepsyassociatedneuroepithelial pages 1-2, rosemberg2023longtermepilepsyassociatedtumors pages 1-2)

1.2 WHO grade and classification context

Multiple WHO-2021 (5th edition) aligned sources list DNET/DNT as WHO grade 1 within LEAT/glioneuronal tumor groupings. (xie2023lowgradeepilepsyassociatedneuroepithelial pages 2-3, xie2023lowgradeepilepsyassociatedneuroepithelial media 10d99c66)

1.3 Synonyms and alternative names

  • Dysembryoplastic neuroepithelial tumor (US spelling) / tumour (UK spelling). (pages2022thegenomiclandscape pages 10-10)
  • Dysembryoplastic neuroepithelial tumor (DNET) / dysembryoplastic neuroepithelial tumour (DNT). (rahim2023clinicopathologicalfeaturesof pages 1-2)
  • Informal clinical term: “epileptoma” (used for highly epileptogenic low-grade tumors such as DNET and ganglioglioma). (khalilov2024atypicalpresentationof pages 1-2)

1.4 Key identifiers (OMIM, Orphanet, ICD-10/ICD-11, MeSH, MONDO)

No explicit OMIM/Orphanet/ICD/MeSH/MONDO identifiers were present in the retrieved full-text evidence set. This report therefore does not assert codes without direct supporting evidence. (rosemberg2023longtermepilepsyassociatedtumors pages 1-2)

1.5 Evidence source type

Most disease-level information here is derived from aggregated literature sources (reviews, cohorts) plus a few case reports/case series and a clinical registry trial record, rather than EHR-only data. (rosemberg2023longtermepilepsyassociatedtumors pages 1-2, rahim2023clinicopathologicalfeaturesof pages 1-2, NCT03970785 chunk 1)

2. Etiology

2.1 Disease causal factors

Primary causal factors are somatic oncogenic alterations, most commonly involving FGFR1 and the downstream MAPK/ERK pathway, consistent with a developmental/circumscribed tumor biology typical for LEATs. (rivera2016germlineandsomatic pages 1-2, rivera2016germlineandsomatic pages 12-15)

Rivera et al. explicitly conclude that “constitutional and somatic FGFR1 alterations and MAP kinase pathway activation are key events in the pathogenesis of DNET,” supporting a molecularly driven etiology. (rivera2016germlineandsomatic pages 1-2)

2.2 Risk factors

Clinical/demographic risk: DNET is predominantly encountered in children/adolescents/young adults (e.g., LEAT seizure onset often around early teens) and occurs supratentorially with temporal predilection, but established population-level environmental risk factors were not identified in the retrieved corpus. (xie2023lowgradeepilepsyassociatedneuroepithelial pages 1-2, rahim2023clinicopathologicalfeaturesof pages 1-2)

Genetic risk: Most evidence supports somatic drivers rather than inherited predisposition; however, a familial scenario with a germline FGFR1 mutation (p.R661P) plus somatic “second hits” was reported, demonstrating a possible (rare) inherited predisposition mechanism in select families. (rivera2016germlineandsomatic pages 1-2)

2.3 Protective factors

No protective genetic variants or environmental protective factors were identified in the retrieved corpus. (rosemberg2023longtermepilepsyassociatedtumors pages 1-2)

2.4 Gene–environment interactions

No gene–environment interaction evidence was identified in the retrieved corpus. (rosemberg2023longtermepilepsyassociatedtumors pages 1-2)

3. Phenotypes (clinical features)

3.1 Core phenotypes (with suggested HPO terms)

DNET is strongly linked to epilepsy; seizures are typically focal and may be drug-resistant. (rahim2023clinicopathologicalfeaturesof pages 1-2, khalilov2024atypicalpresentationof pages 1-2)

Key phenotypes: * Focal seizures / epilepsy (often drug-resistant) — suggested HPO: HP:0001250 (Seizures); HP:0002197 (Generalized seizures) when present; HP:0007359 (Focal seizures) (term name may vary by HPO release). (xie2023lowgradeepilepsyassociatedneuroepithelial pages 1-2, rahim2023clinicopathologicalfeaturesof pages 1-2) * Headache can occur, including rare presentations without epilepsy — suggested HPO: HP:0002315 (Headache). (khalilov2024atypicalpresentationof pages 1-2)

3.2 Phenotype characteristics (age of onset, severity, progression)

  • Age of onset: LEATs typically have seizure onsets at a young age (commonly cited ~12–15 years) and DNETs are described as occurring in children/adolescents and young adults. (xie2023lowgradeepilepsyassociatedneuroepithelial pages 1-2, rahim2023clinicopathologicalfeaturesof pages 1-2)
  • Progression: biologically stable/benign course is typical, with rare malignant transformation. (khalilov2024atypicalpresentationof pages 1-2, zhang2022longtermseizureoutcomes pages 1-2)

Quantitative examples from a 2023 case series (Pakistan; n=14): age range 9–45 years (mean 19), seizure duration pre-resection 2 months to 9 years (mean 3.2 years), with temporal and frontal lobes most common sites. (rahim2023clinicopathologicalfeaturesof pages 1-2)

3.3 Quality of life impact

Seizures are commonly chronic and may be refractory, motivating epilepsy surgery; thus, DNET can substantially impact function through seizure burden (school/work limitations and medication adverse effects), although disease-specific validated QOL metrics were not extracted from the retrieved corpus. (rosemberg2023longtermepilepsyassociatedtumors pages 1-2, avila2024braintumorrelatedepilepsy pages 10-11)

4. Genetic/Molecular Information

4.1 Causal genes and pathways

The dominant molecular theme is RTK → RAS/MAPK/ERK activation, with FGFR1 as a key oncogenic driver in many DNETs; subsets also show alterations converging on PI3K/mTOR. (rivera2016germlineandsomatic pages 1-2, surrey2019genomicanalysisof pages 1-1)

4.2 Pathogenic variants and alteration types (somatic vs germline)

FGFR1 alterations in DNET include: * Hotspot missense mutations (e.g., p.N546K, p.K656E) (rivera2016germlineandsomatic pages 1-2, lucas2020comprehensiveanalysisof pages 1-2) * Tyrosine kinase domain duplication / internal tandem duplication (ITD) (rivera2016germlineandsomatic pages 1-2, pages2022thegenomiclandscape pages 10-10) * Rare fusions/breakpoints involving FGFR1 (rivera2016germlineandsomatic pages 12-15, pages2022thegenomiclandscape pages 10-10)

Somatic vs germline: Rivera et al. provide explicit evidence of both, reporting a germline FGFR1 p.R661P with somatic activating FGFR1 hotspot mutations (p.N546K or p.K656E) in tumor, including a case where p.K656E occurred in cis with the germline variant. (rivera2016germlineandsomatic pages 1-2)

4.3 Frequencies/statistics for molecular alterations

Well-curated DNET cohorts show high enrichment of FGFR1 alterations: * In a neuropathology-confirmed cohort (43 cases), FGFR1 alterations were frequent and “mainly comprised intragenic tyrosine kinase FGFR1 duplication and multiple mutants in cis (25/43; 58.1%) while BRAF p.V600E alterations were absent (0/43).” (rivera2016germlineandsomatic pages 1-2) * In a cohort of 58 “specific” DNTs, Pagès et al. report FGFR1 disruption (mutation, ITD, fusion) and state “In our cohort of 58 specific DNTs, we found a similar frequency (68%)” (of FGFR1-related events). (pages2022thegenomiclandscape pages 10-10)

Broader DNT/MNGT spectrum sequencing shows that alterations frequently converge on MAPK/PI3K signaling; in one series, “more than half” (19/33) of analyzed tumors had alterations predicted to dysregulate MAPK and/or PI3K pathways. (surrey2019genomicanalysisof pages 1-1)

4.4 Other drivers and rare events

  • NTRK2 fusion: A DNET case reported a novel LHFPL3::NTRK2 fusion retaining the NTRK2 tyrosine kinase domain; authors describe likely pathogenicity through constitutive RTK signaling. (chen2022casereporta pages 1-2)
  • BRAF V600E: Literature reports exist, but BRAF V600E may be absent in some well-curated “specific DNT” cohorts (e.g., none detected in two cohorts summarized above). (rivera2016germlineandsomatic pages 1-2, pages2022thegenomiclandscape pages 10-10)

4.5 Epigenetic information

DNA methylation profiling is increasingly used for difficult-to-classify low-grade neuroepithelial tumors and can support/refine diagnosis beyond morphology alone; however, DNET-specific methylation subclass statistics were not available from the retrieved evidence set. (gatesman2024characterizationoflow‐grade pages 1-2)

5. Environmental Information

No validated environmental/lifestyle/infectious causal factors were identified for DNET in the retrieved corpus. (rosemberg2023longtermepilepsyassociatedtumors pages 1-2)

6. Mechanism / Pathophysiology

6.1 Causal chain (molecular → cellular → clinical)

A commonly supported mechanistic chain is: 1) FGFR1 activation (hotspot mutation, ITD/kinase duplication, or fusion) → 2) increased MAPK/ERK signaling (phospho-ERK upregulation) → 3) tumor formation/maintenance in cortex (glioneuronal tumor microenvironment) → 4) cortical network hyperexcitability and epileptogenesis, clinically manifesting as focal seizures and drug-resistant epilepsy; seizure burden is also influenced by the epileptogenic zone extending into peritumoral cortex and co-existing focal cortical dysplasia (“dual pathology”). (rivera2016germlineandsomatic pages 12-15, xie2023lowgradeepilepsyassociatedneuroepithelial pages 1-2, bonney2016reviewofseizure pages 4-5)

Rivera et al. provide functional support for MAPK activation: phospho-ERK was upregulated in FGFR1-mutated cases and they report immunohistochemical confirmation of phospho-ERK upregulation in “24/35 (69%)” of FGFR1-mutated cases. (rivera2016germlineandsomatic pages 12-15)

6.2 Upstream vs downstream mechanisms

  • Upstream: receptor tyrosine kinase (FGFR1) activating events; rare RTK fusions (e.g., NTRK2) (rivera2016germlineandsomatic pages 1-2, chen2022casereporta pages 1-2)
  • Downstream: MAPK/ERK and sometimes PI3K/mTOR pathway dysregulation (surrey2019genomicanalysisof pages 1-1, rivera2016germlineandsomatic pages 12-15)

6.3 Cell types (suggested CL terms) and biological processes (suggested GO terms)

The tumor is glioneuronal, implicating glial-lineage and neuronal components and peritumoral neuronal circuitry.

Suggested Cell Ontology (CL) terms (examples): * CL:0000540 (Neuron) for epileptogenic network effects and “floating neurons” concept (pathology context). (rahim2023clinicopathologicalfeaturesof pages 1-2) * CL:0000127 (Astrocyte) and CL:0000128 (Oligodendrocyte) as relevant to glial components/oligodendrocyte-like cells described histologically. (rahim2023clinicopathologicalfeaturesof pages 1-2)

Suggested GO Biological Process terms (examples): * MAPK cascade (e.g., GO:0000165) and ERK1/2 cascade (relevant to phospho-ERK evidence). (rivera2016germlineandsomatic pages 12-15) * Regulation of synaptic transmission / neuronal excitability (epileptogenesis context; general). (avila2024braintumorrelatedepilepsy pages 10-11)

7. Anatomical Structures Affected

7.1 Organ/system level

Primary system affected is the central nervous system (brain), with seizures as the dominant symptom. (rahim2023clinicopathologicalfeaturesof pages 1-2, xie2023lowgradeepilepsyassociatedneuroepithelial pages 1-2)

7.2 Localization (suggested UBERON terms)

DNET is typically supratentorial and cortical with strong temporal lobe predominance and frequent frontal involvement. (rahim2023clinicopathologicalfeaturesof pages 1-2, xie2023lowgradeepilepsyassociatedneuroepithelial pages 1-2)

Suggested UBERON terms (examples): * UBERON:0000955 (brain) * UBERON:0001870 (cerebral cortex) * UBERON:0002285 (temporal lobe) * UBERON:0001871 (frontal lobe)

7.3 Tissue/cell level and subcellular components

A frequent associated lesion is focal cortical dysplasia adjacent to tumor (dual pathology), implicating both tumor and surrounding cortex. (khalilov2024atypicalpresentationof pages 1-2)

8. Temporal Development

8.1 Onset

DNETs are described as occurring most often in childhood/adolescence; LEAT seizures commonly begin in early teens and frequently precede surgery by years. (xie2023lowgradeepilepsyassociatedneuroepithelial pages 1-2, rahim2023clinicopathologicalfeaturesof pages 1-2)

8.2 Progression/course

Tumors are usually slow-growing/indolent with long seizure histories; malignant transformation is rare. (xie2023lowgradeepilepsyassociatedneuroepithelial pages 1-2, zhang2022longtermseizureoutcomes pages 1-2)

9. Inheritance and Population

9.1 Epidemiology

Quantitative epidemiology is limited but a large surgical cohort review reports DNET incidence around 0.03/100,000/year (US estimate) and highlights that DNET constitutes a substantial fraction of LEAT diagnoses in epilepsy surgery series. (zhang2022longtermseizureoutcomes pages 1-2, iijima2024genotyperelevantneuroimagingfeatures pages 1-2)

9.2 Inheritance

DNET is primarily driven by somatic alterations, but rare familial predisposition via germline FGFR1 alteration has been reported. (rivera2016germlineandsomatic pages 1-2)

10. Diagnostics

10.1 Clinical workup

Diagnosis is typically based on seizure history plus MRI and confirmatory histopathology; preoperative epilepsy workup commonly includes long-term video-EEG, with additional modalities (MEG, PET, invasive monitoring) when needed to define the epileptogenic zone. (zhang2022longtermseizureoutcomes pages 2-5, takayama2022ishippocampalresection pages 1-2)

10.2 Imaging

MRI is emphasized as the key modality; lesions are often cortical-based and may be classified into morphologic patterns (e.g., cystic-like, nodular-like, dysplastic-like). (zhang2022longtermseizureoutcomes pages 2-5, rahim2023clinicopathologicalfeaturesof pages 1-2)

A 2024 radiogenomic study in LEATs showed that certain imaging patterns can predict genotype with high accuracy, reporting imaging groups with “93.8% sensitivity and 100% specificity to BRAF V600E” (Group 1) and “100% sensitivity and specificity for FGFR1 mutations” (Group 2). (iijima2024genotyperelevantneuroimagingfeatures pages 1-2)

10.3 Histopathology

Characteristic pathology includes a multinodular architecture and “floating neurons” within a specific glioneuronal element; Ki-67 is typically very low. (rahim2023clinicopathologicalfeaturesof pages 1-2)

10.4 Molecular diagnostics (NGS, methylation)

Molecular profiling supports diagnosis and may clarify difficult cases, particularly in the DNT/MNGT/PLNTY spectrum where morphology overlaps; testing may include targeted DNA/RNA sequencing for FGFR1/BRAF/NTRK alterations and methylation arrays. (surrey2019genomicanalysisof pages 1-1, gatesman2024characterizationoflow‐grade pages 1-2)

A 2024 proof-of-concept study demonstrated feasibility of extracting tumor DNA from tissue adherent to stereoelectroencephalography (sEEG) electrodes and performing targeted sequencing and DNA methylation array analysis to aid classification. (gatesman2024characterizationoflow‐grade pages 1-2)

11. Outcome/Prognosis

11.1 Seizure outcomes after surgery (key quantitative data)

In a 63-patient DNET cohort (2008–2021), 49/63 (77.8%) were seizure-free after surgery, with cumulative seizure recurrence-free rates 82.5% (2 years), 79.0% (5 years), 76.5% (10 years). (zhang2022longtermseizureoutcomes pages 1-2)

A systematic review of surgical series reported a median seizure-freedom rate of 86% (IQR 77–93%) and highlighted that gross-total resection is repeatedly associated with seizure freedom. (bonney2016reviewofseizure pages 4-5)

11.2 Prognostic factors

Predictors of better seizure outcomes include gross total resection and shorter epilepsy duration, while certain imaging patterns (e.g., dysplastic-like) and bilateral interictal epileptiform discharges may predict poorer seizure outcomes. (zhang2022longtermseizureoutcomes pages 1-2)

12. Treatment

12.1 Surgical and interventional (standard of care)

Maximal safe surgical resection/lesionectomy is widely considered the optimal approach to achieve seizure control and durable tumor control in LEATs, including DNET. (xie2023lowgradeepilepsyassociatedneuroepithelial pages 1-2)

A hippocampus-sparing strategy may be appropriate in selected temporal-lobe LEATs with normal hippocampus: in a cohort of 32 temporal LEAT cases, 28/32 (87.5%) achieved seizure freedom irrespective of hippocampal resection, and additional hippocampal resection negatively impacted verbal outcomes. (takayama2022ishippocampalresection pages 1-2)

Real-world implementation example: an observational clinical registry study evaluated intraoperative fluorescein-guided resection feasibility for ganglioglioma and DNET (NCT03970785), using surgical video review and postoperative MRI to assess fluorescence and extent of resection, with Engel-classification seizure outcomes. (NCT03970785 chunk 1)

12.2 Pharmacotherapy: antiseizure medications (ASMs)

DNET-associated epilepsy is frequently treated with ASMs but may be drug-resistant; consensus neuro-oncology practice avoids routine prophylactic ASM use in seizure-naïve patients. (rahim2023clinicopathologicalfeaturesof pages 1-2, avila2024braintumorrelatedepilepsy pages 10-11)

A 2024 Society for Neuro-Oncology consensus review states prophylactic ASM in seizure-naïve brain tumor patients lacks high-quality evidence, yet ~70% of neurosurgeons give a short postoperative course (commonly levetiracetam for 7 days after supratentorial craniotomy); meta-analysis showed reduced early postoperative seizures (RR 0.35, 95% CI 0.13–0.95) but not late seizures. (avila2024braintumorrelatedepilepsy pages 10-11)

Newton & Wojkowski (2024) summarize that seizures affect >50% of brain tumor patients overall and provide tumor-specific estimates (DNET ~100%), and similarly advise that prophylactic AEDs are not recommended; after a first verified seizure, consensus is to start ASM monotherapy, most often levetiracetam (with alternatives/add-ons including lacosamide, valproate, brivaracetam, lamotrigine, and perampanel). (newton2024antiepilepticstrategiesfor pages 1-3)

12.3 Targeted/experimental therapy

Because DNET biology is frequently MAPK-driven (FGFR1 alterations, RTK fusions), MEK-pathway targeting is being evaluated within broader pediatric/AYA low-grade glioma frameworks.

Clinical trial example (MAPK-pathway therapy): SJ901 (NCT04923126) evaluates mirdametinib (MEK1/2 inhibitor) in pediatric/AYA low-grade glioma and explicitly includes LEAT histologies such as dysembryoplastic neuroepithelial tumor (DNET) among eligible conditions; a separate protocol chunk specifies requirement for centrally reviewed MAPK-pathway activation evidence (including FGFR1/2/3 aberrations and other RAS/MAPK genes). (NCT04923126 chunk 2, NCT04923126 chunk 4)

12.4 Suggested MAXO (Medical Action Ontology) terms

Because MAXO codes were not present in the evidence corpus, the following are suggested as likely appropriate mappings (to be verified against MAXO): * Neurosurgical resection of brain tumor (lesionectomy/gross total resection). (xie2023lowgradeepilepsyassociatedneuroepithelial pages 1-2) * Antiseizure medication therapy (levetiracetam monotherapy; add-on therapy). (avila2024braintumorrelatedepilepsy pages 10-11) * Stereoelectroencephalography (SEEG) monitoring / intracranial EEG evaluation. (gatesman2024characterizationoflow‐grade pages 1-2) * Intraoperative fluorescence-guided surgery. (NCT03970785 chunk 1) * MEK inhibitor therapy (mirdametinib clinical trial context). (NCT04923126 chunk 2)

13. Prevention

No primary-prevention interventions are established for DNET based on available evidence; secondary prevention in practice is largely early recognition of epileptogenic lesions and timely referral for epilepsy surgery evaluation when seizures are drug-resistant. (xie2023lowgradeepilepsyassociatedneuroepithelial pages 1-2)

14. Other Species / Natural Disease

No naturally occurring DNET analogue in non-human species was identified in the retrieved corpus. (rosemberg2023longtermepilepsyassociatedtumors pages 1-2)

15. Model Organisms

A 2024 review on epilepsy-associated tumors notes improving animal modeling capacity for low-grade neuroepithelial tumors (LGNTs) with tools such as in utero electroporation to generate tumors with relevant genetic features; however, DNET-specific validated model organism details were not extracted from the retrieved evidence set. (rahim2023clinicopathologicalfeaturesof pages 6-7)

Recent developments and expert analysis (2023–2024 emphasis)

2023–2024: classification and diagnostic modernization

Recent LEAT-focused reviews emphasize that DNET is a core LEAT entity and that the WHO CNS 2021 classification recognized additional epilepsy-associated tumor entities, increasing the importance of integrated diagnosis using histology plus molecular tools. (rosemberg2023longtermepilepsyassociatedtumors pages 1-2, xie2023lowgradeepilepsyassociatedneuroepithelial pages 1-2)

A WHO-2021-based LEAT table explicitly lists DNET as WHO grade 1 with characteristic genetic alteration FGFR1, supporting a molecularly anchored diagnostic approach rather than morphology alone. (xie2023lowgradeepilepsyassociatedneuroepithelial media 10d99c66)

2024: radiogenomics and minimally invasive molecular profiling

The 2024 radiogenomic study provides a practical framework suggesting that preoperative neuroimaging patterns can predict genotype, potentially enabling earlier precision planning (e.g., anticipating FGFR1 vs BRAF-driven lesions), and also indicates seizure outcomes may differ by genotype-associated imaging group. (iijima2024genotyperelevantneuroimagingfeatures pages 1-2)

A 2024 proof-of-concept sEEG-electrode approach suggests that neurosurgical epilepsy workflows can also become molecular diagnostic workflows, enabling targeted sequencing and methylation analysis from microscopic tissue without requiring a separate biopsy procedure. (gatesman2024characterizationoflow‐grade pages 1-2)

2024: consensus TRE management

The 2024 SNO consensus emphasizes evidence-based antiseizure management principles that generalize to DNET patients (especially perioperative decisions): no strong support for routine prophylaxis in seizure-naïve cases, frequent use of short postoperative levetiracetam courses, preference for monotherapy and non–enzyme-inducing ASMs, and escalation toward local therapies (surgery/irradiation) for drug-resistant seizures. (avila2024braintumorrelatedepilepsy pages 10-11)

URLs and publication dates (selected key sources)

  • Rahim et al. “Clinicopathological features of dysembryoplastic neuroepithelial tumor: a case series” (2023-08). https://doi.org/10.1186/s13256-023-04062-1 (rahim2023clinicopathologicalfeaturesof pages 1-2)
  • Khalilov et al. “Atypical presentation of dysembryoplastic neuroepithelial tumor” (2024-10). https://doi.org/10.17816/acen.1126 (khalilov2024atypicalpresentationof pages 1-2)
  • Iijima et al. “Genotype-relevant neuroimaging features in low-grade epilepsy-associated tumors” (2024-07). https://doi.org/10.3389/fneur.2024.1419104 (iijima2024genotyperelevantneuroimagingfeatures pages 1-2)
  • Avila et al. SNO consensus “Brain tumor-related epilepsy management…” (2024-09). https://doi.org/10.1093/neuonc/noad154 (avila2024braintumorrelatedepilepsy pages 10-11)
  • Newton & Wojkowski “Antiepileptic strategies…” (2024-02). https://doi.org/10.1007/s11864-024-01182-8 (newton2024antiepilepticstrategiesfor pages 1-3)
  • ClinicalTrials.gov NCT03970785 (first posted 2019-06-03; study 2015–2018 cases): https://clinicaltrials.gov/study/NCT03970785 (NCT03970785 chunk 1)
  • ClinicalTrials.gov NCT04923126 (first posted 2021-06-18): https://clinicaltrials.gov/study/NCT04923126 (NCT04923126 chunk 2)

Evidence gaps and limitations (for knowledge-base curation)

  • Formal external identifiers (MeSH, ICD-10/11, Orphanet, MONDO, OMIM) were not retrievable from the current evidence set; they should be added from dedicated ontology resources (not inferred). (rosemberg2023longtermepilepsyassociatedtumors pages 1-2)
  • DNET-specific methylation subclass definitions and epigenetic prognostic biomarkers were not extractable from the retrieved texts; further targeted retrieval of DKFZ classifier class descriptions and DNET methylation studies would be needed. (gatesman2024characterizationoflow‐grade pages 1-2)
  • Non-human natural disease and validated DNET-specific model organism details were not identified in the retrieved corpus. (rahim2023clinicopathologicalfeaturesof pages 6-7)

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