Mixed Neuronal-Glial Tumor

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Subtypes

6

Ganglioglioma MONDO:0016733

Most common mixed neuronal-glial tumor; CNS WHO grade 1. Composed of dysmorphic neoplastic neuronal (ganglion) cells admixed with a neoplastic glial component. Driven most often by BRAF p.V600E, with less frequent FGFR1, KRAS, NF1, H3-3A, or RAF1 alterations. Typically presents with long-standing focal epilepsy, often temporal lobe.

Show evidence (1 reference)

PMID:35512827 SUPPORT Human Clinical

"While ganglioglioma, dysembryoplastic neuroepithelial tumor, and desmoplastic infantile tumor are common glioneuronal tumors, anaplastic ganglioglioma, papillary glioneuronal tumor, rosette-forming glioneuronal tumor, gangliocytoma, and central neurocytoma are less frequent."

Establishes ganglioglioma as one of the common glioneuronal tumor subtypes.

Gangliocytoma MONDO:0016730

CNS WHO grade 1 neuronal tumor composed of dysplastic mature ganglion cells without a neoplastic glial component, on the same biological spectrum as ganglioglioma. Less frequent than ganglioglioma; associated with epilepsy.

Show evidence (1 reference)

PMID:35512827 SUPPORT Human Clinical

"anaplastic ganglioglioma, papillary glioneuronal tumor, rosette-forming glioneuronal tumor, gangliocytoma, and central neurocytoma are less frequent."

Lists gangliocytoma among the less-frequent glioneuronal/neuronal tumor subtypes.

Dysembryoplastic Neuroepithelial Tumor (DNET) MONDO:0005505

CNS WHO grade 1 glioneuronal tumor defined by the "specific glioneuronal element" with columns of oligodendrocyte-like cells in a myxoid matrix and "floating neurons". FGFR1 alterations are present in the majority (>75%) of cases. Presents with drug-resistant epilepsy from cortical, often temporal, lesions.

Show evidence (1 reference)

PMID:35018490 SUPPORT Human Clinical

"Five tumors were classified as dysembryoplastic neuroepithelial tumor (DNT), 4 as pilocytic astrocytoma (PA) and 3 as rosette-forming glioneuronal tumor (RGNT). FGFR1 mutations were associated with oligodendroglia-like cells"

Documents FGFR1 hotspot mutations in DNET and their association with the oligodendrocyte-like cells characteristic of DNET.

Papillary Glioneuronal Tumor MONDO:0016735

CNS WHO grade 1 glioneuronal tumor with a pseudopapillary architecture lined by GFAP-positive glial cells and interpapillary synaptophysin-positive neuronal cells. Characterized molecularly by the SLC44A1::PRKCA fusion. Usually presents in young adults with seizures and/or headaches from a circumscribed supratentorial mass.

Show evidence (1 reference)

PMID:35512827 SUPPORT Human Clinical

"anaplastic ganglioglioma, papillary glioneuronal tumor, rosette-forming glioneuronal tumor, gangliocytoma, and central neurocytoma are less frequent."

Identifies papillary glioneuronal tumor as one of the less-frequent glioneuronal tumor subtypes.

Rosette-Forming Glioneuronal Tumor (RGNT) MONDO:0016736

CNS WHO grade 1 glioneuronal tumor with neurocytic rosettes and perivascular pseudorosettes alongside an astrocytic component, typically arising in the posterior fossa / fourth-ventricle region. Driven by FGFR1 hotspot mutations, often with PIK3CA, PIK3R1, or NF1 co-alterations. Presents more often with headache, ataxia, and hydrocephalus than with epilepsy.

Show evidence (1 reference)

PMID:35018490 SUPPORT Human Clinical

"Five tumors were classified as dysembryoplastic neuroepithelial tumor (DNT), 4 as pilocytic astrocytoma (PA) and 3 as rosette-forming glioneuronal tumor (RGNT)."

Documents FGFR1 hotspot mutations identified in rosette-forming glioneuronal tumor cases.

Desmoplastic Infantile Ganglioglioma (DIG) MONDO:0022965

CNS WHO grade 1 infantile glioneuronal tumor with a prominent desmoplastic stroma containing astroglial and neuronal/ganglion cell elements. Presents in infancy (usually within the first 2 years of life), typically as a large superficial cystic/solid mass causing macrocephaly, an enlarging head circumference, and signs of raised intracranial pressure.

Show evidence (1 reference)

PMID:35512827 SUPPORT Human Clinical

"While ganglioglioma, dysembryoplastic neuroepithelial tumor, and desmoplastic infantile tumor are common glioneuronal tumors"

Identifies desmoplastic infantile tumor (desmoplastic infantile ganglioglioma) among the glioneuronal tumors.

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Pathophysiology

4

MAPK Pathway Activation

The initiating and central pathogenic event is a somatic genetic alteration that constitutively activates the RAS-RAF-MEK-ERK (MAPK) signaling cascade. In ganglioglioma the dominant driver is the BRAF p.V600E missense mutation (glutamic acid-to-valine substitution in the kinase domain), while in DNET and other entities FGFR1 hotspot mutations (N546K, K656E) predominate; FGFR1 activation simultaneously stimulates the RAS/RAF/MEK and PI3K-AKT cascades. These low-grade glioneuronal tumors are considered developmental neoplasms arising from MAPK-activated neural progenitors rather than from environmental exposures.

neural progenitor cell CL:0011020

BRAF hgnc:1097

MAPK cascade GO:0000165 ↑ INCREASED positive regulation of cell proliferation GO:0008284 ↑ INCREASED negative regulation of apoptosis GO:0043066 ↑ INCREASED

Downstream

Dual Neuronal-Glial Differentiation Constitutive MAPK activation in neural progenitors during development drives aberrant proliferation and dual differentiation toward both neuronal and glial lineages, producing the characteristic mixed cellular composition.

Show evidence (2 references)

PMID:35018490 SUPPORT Human Clinical

"Low-grade gliomas (LGG) and mixed neuronal-glial tumors (MNGT) show frequent MAPK pathway alterations."

Establishes that MAPK pathway alterations are the frequent, shared molecular driver of mixed neuronal-glial tumors.

PMID:41721014 SUPPORT Human Clinical

"The most common mutation was BRAFV600E present in 36.94%, followed by the mutation in FGFR1, reported in 1.18% of cases."

Systematic review of 1360 gangliogliomas establishes BRAF V600E as the most common MAPK-activating driver, with FGFR1 next.

Dual Neuronal-Glial Differentiation

Aberrant differentiation of MAPK-activated neural progenitors yields a neoplasm containing both a neoplastic neuronal component (dysmorphic ganglion cells, floating neurons, or neurocytic rosettes depending on subtype) and a neoplastic glial component (astrocytic GFAP-positive and/or oligodendrocyte-like OLIG2-positive cells). This dual lineage is the defining histological feature of glioneuronal tumors and distinguishes them from pure gliomas.

neoplastic neuron CL:0000540 neoplastic astrocyte CL:0000127 neoplastic oligodendrocyte-like cell CL:0000128

neuron differentiation GO:0030182 ⚠ ABNORMAL cell fate determination GO:0001709 ⚠ ABNORMAL

Downstream

Cortical Low-Grade Neoplasm The mixed neuronal-glial proliferation forms a circumscribed, slow-growing (CNS WHO grade 1) tumor, typically in the cerebral cortex with a predilection for the temporal and frontal lobes.

Show evidence (1 reference)

PMID:35512827 SUPPORT Human Clinical

"Glioneuronal tumors are characterized exclusively by neurocytic elements (neuronal tumors) or a combination of neuronal and glial features (mixed neuronal-glial tumors)."

Defines the dual neuronal and glial composition that characterizes mixed neuronal-glial tumors.

Cortical Low-Grade Neoplasm

A circumscribed, indolent (most commonly CNS WHO grade 1) neoplasm situated in the cerebral cortex, most often the temporal lobe. The cortical/subcortical location and intimate relationship with surrounding cortex underlie both the typical seizure presentation and the favorable outcome after gross total resection.

cerebral cortex UBERON:0000956 temporal lobe UBERON:0001871

Downstream

Epileptogenic Cortical Disruption The cortical tumor, frequently associated with adjacent focal cortical dysplasia, disrupts local cortical circuitry and creates an epileptogenic zone with high intrinsic epileptogenic potential.

Show evidence (1 reference)

PMID:36831464 SUPPORT Human Clinical

"Rare glial, neuronal and glioneuronal tumours in adults form a heterogeneous group of rare, primary central nervous system tumours."

Establishes glioneuronal tumors as a group of primary CNS (brain) neoplasms.

Epileptogenic Cortical Disruption

Glioneuronal tumors, particularly ganglioglioma and DNET, are among the most common causes of drug-resistant focal epilepsy. The intimate cortical location, abnormal neuronal differentiation, and frequent association with focal cortical dysplasia generate a highly epileptogenic substrate, such that these tumors have been informally termed "epileptomas".

cerebral cortex UBERON:0000956

Downstream

Drug-Resistant Focal Epilepsy The epileptogenic cortical substrate manifests clinically as chronic, frequently drug-resistant focal seizures, the dominant presenting phenotype of these tumors.

Show evidence (1 reference)

PMID:34196984 SUPPORT Human Clinical

"Structural brain lesions, including the broad range of malformations of cortical development (MCD) and glioneuronal tumors, are among the most common causes of drug-resistant focal epilepsy."

Establishes glioneuronal tumors as a leading structural cause of drug-resistant focal epilepsy via cortical disruption.

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Pathograph

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Phenotypes

6

Head and Neck 1

Macrocephaly Macrocephaly HP:0000256

Nervous System 4

Drug-Resistant Focal Epilepsy Focal-onset seizure HP:0007359

Temporal: CHRONIC

Show evidence (2 references)

PMID:34196984 SUPPORT Human Clinical

"Structural brain lesions, including the broad range of malformations of cortical development (MCD) and glioneuronal tumors, are among the most common causes of drug-resistant focal epilepsy."

Documents drug-resistant focal epilepsy as a hallmark phenotype caused by glioneuronal tumors.

PMID:35512827 SUPPORT Human Clinical

"Most of these tumors occur in young patients and are related to epilepsy."

Supports the strong association of glioneuronal tumors with epilepsy and young age of onset.

Seizure Seizure HP:0001250

Show evidence (1 reference)

PMID:35512827 SUPPORT Human Clinical

"Most of these tumors occur in young patients and are related to epilepsy."

Supports seizures as a characteristic phenotype of glioneuronal tumors.

Headache Headache HP:0002315

Hydrocephalus Hydrocephalus HP:0000238

Other 1

CNS Glioneuronal Neoplasm Neuronal/glioneuronal neoplasm of the central nervous system HP:0025170

Show evidence (1 reference)

PMID:35512827 SUPPORT Human Clinical

"Glioneuronal tumors are characterized exclusively by neurocytic elements (neuronal tumors) or a combination of neuronal and glial features (mixed neuronal-glial tumors)."

Defines the entity as a CNS glioneuronal neoplasm.

🧬

Genetic Associations

2

BRAF (Most common somatic driver mutation (p.V600E))

Gene: BRAF hgnc:1097 relationship_type: SOMATIC_DRIVER variant_origin: SOMATIC

Show evidence (1 reference)

PMID:41721014 SUPPORT Human Clinical

"The most common mutation was BRAFV600E present in 36.94%, followed by the mutation in FGFR1, reported in 1.18% of cases."

Quantifies BRAF V600E as the most frequent somatic alteration in gangliogliomas.

FGFR1 (Dominant somatic driver in DNET and RGNT; rare in ganglioglioma)

Gene: FGFR1 hgnc:3688 relationship_type: SOMATIC_DRIVER variant_origin: SOMATIC

Show evidence (1 reference)

PMID:35018490 SUPPORT Human Clinical

"FGFR1 hotspot mutations are the fifth most prevailing alteration in LGG/MNGT. Performing FGFR1 sequencing analysis in driver-unknown low-grade brain tumors could yield up to 12% FGFR1 N546/K656 mutant cases."

Establishes FGFR1 hotspot mutations as a recurrent driver of mixed neuronal-glial tumors.

💊

Medical Actions

3

Surgical Resection

Action: surgical procedure MAXO:0000004

Gross total surgical resection is the cornerstone of treatment and is considered curative for most CNS WHO grade 1 glioneuronal tumors. For epilepsy-associated tumors, extended resection that includes the epileptogenic zone improves seizure-free outcomes.

Mechanism Target:

BYPASSES Cortical Low-Grade Neoplasm — Resection physically removes the cortical tumor and epileptogenic substrate, addressing both the neoplasm and the seizures.

BRAF/MEK Inhibitor Targeted Therapy

Action: Pharmacotherapy NCIT:C15986

For BRAF p.V600E-mutant tumors that are progressive, recurrent, or unresectable, combined BRAF and MEK inhibition (e.g., dabrafenib plus trametinib) is the preferred targeted approach; BRAF V600E is the only molecular target of proven clinical benefit in adult gliomas/glioneuronal tumors per EANO. In a multi-institutional series of BRAF-mutant pediatric high-grade gliomas (including anaplastic gangliogliomas) treated upfront, 3-year progression-free and overall survival were 65% and 82%.

Mechanism Target:

INHIBITS MAPK Pathway Activation — BRAF and MEK inhibitors block constitutive RAS-RAF-MEK-ERK signaling driven by the BRAF V600E mutation.

Show evidence (2 references)

PMID:39387386 SUPPORT Human Clinical

"From all targets reviewed, only testing for BRAF V600E mutations was of proven clinical benefit"

EANO guideline update establishes BRAF V600E as the only target of proven clinical benefit, justifying BRAF-directed therapy.

PMID:35397478 SUPPORT Human Clinical

"three-year progression-free and overall survival for the cohort were 65% and 82%, respectively, and superior to a historical control cohort of BRAF-mutant pHGG patients treated with conventional therapies."

Demonstrates efficacy of upfront BRAF/MEK targeted therapy in BRAF-mutant tumors including anaplastic ganglioglioma.

Radiation Therapy

Action: radiation therapy MAXO:0000014

Radiotherapy is reserved for subtotally resected aggressive tumors, tumors in eloquent areas, or recurrent disease, and is used cautiously in young children because of long-term cognitive sequelae.

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Clinical Trials

1

NCT02684058 PHASE_II COMPLETED

Dabrafenib plus trametinib in pediatric patients with BRAF V600 mutation-positive low-grade glioma or relapsed high-grade glioma.

Target Phenotypes: Seizure HP:0001250

Show evidence (1 reference)

clinicaltrials:NCT02684058 SUPPORT Human Clinical

"The purpose of this study was to investigate the activity of dabrafenib in combination with trametinib in children and adolescent patients with BRAF V600 mutation positive low grade glioma (LGG) or relapsed or refractory high grade glioma (HGG)"

Trial evaluating BRAF/MEK inhibition in BRAF V600-mutant pediatric CNS tumors relevant to BRAF-mutant glioneuronal tumors.

{ }

Source YAML

click to show

name: Mixed Neuronal-Glial Tumor
creation_date: "2026-06-30T00:00:00Z"
category: Complex
description: >-
  Mixed neuronal-glial tumors (glioneuronal tumors) are a heterogeneous family of
  rare, predominantly low-grade (CNS WHO grade 1) primary central nervous system
  neoplasms composed of both neuronal and glial cell populations. They represent
  less than 2% of all primary CNS tumors, predominantly affect children and young
  adults, show a strong predilection for the temporal and frontal cortex, and are
  characterized by a frequent, often drug-resistant, focal epilepsy. Their shared
  pathogenic theme is somatic activation of the RAS-RAF-MEK-ERK (MAPK) signaling
  pathway, most commonly BRAF p.V600E in ganglioglioma and FGFR1 hotspot
  alterations in dysembryoplastic neuroepithelial tumor (DNET). The 2021 WHO CNS5
  classification reorganized these entities into the "glioneuronal and neuronal
  tumors" family using integrated histological, immunohistochemical, and molecular
  (including DNA methylation) criteria.
disease_term:
  preferred_term: mixed neuronal-glial tumor
  term:
    id: MONDO:0016729
    label: mixed neuronal-glial tumor
parents:
- neuroepithelial neoplasm
references:
- reference: PMID:36831464
  title: "Rare Neuronal, Glial and Glioneuronal Tumours in Adults."
- reference: PMID:35218102
  title: "The 2021 WHO Classification of Tumors of the Central Nervous System: An update on pediatric low-grade gliomas and glioneuronal tumors."
has_subtypes:
- name: Ganglioglioma
  description: >-
    Most common mixed neuronal-glial tumor; CNS WHO grade 1. Composed of dysmorphic
    neoplastic neuronal (ganglion) cells admixed with a neoplastic glial component.
    Driven most often by BRAF p.V600E, with less frequent FGFR1, KRAS, NF1, H3-3A,
    or RAF1 alterations. Typically presents with long-standing focal epilepsy,
    often temporal lobe.
  subtype_term:
    preferred_term: ganglioglioma
    term:
      id: MONDO:0016733
      label: ganglioglioma
  evidence:
  - reference: PMID:35512827
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "While ganglioglioma, dysembryoplastic neuroepithelial tumor, and desmoplastic infantile tumor are common glioneuronal tumors, anaplastic ganglioglioma, papillary glioneuronal tumor, rosette-forming glioneuronal tumor, gangliocytoma, and central neurocytoma are less frequent."
    explanation: Establishes ganglioglioma as one of the common glioneuronal tumor subtypes.
- name: Gangliocytoma
  description: >-
    CNS WHO grade 1 neuronal tumor composed of dysplastic mature ganglion cells
    without a neoplastic glial component, on the same biological spectrum as
    ganglioglioma. Less frequent than ganglioglioma; associated with epilepsy.
  subtype_term:
    preferred_term: gangliocytoma
    term:
      id: MONDO:0016730
      label: gangliocytoma
  evidence:
  - reference: PMID:35512827
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "anaplastic ganglioglioma, papillary glioneuronal tumor, rosette-forming glioneuronal tumor, gangliocytoma, and central neurocytoma are less frequent."
    explanation: Lists gangliocytoma among the less-frequent glioneuronal/neuronal tumor subtypes.
- name: DNET
  display_name: Dysembryoplastic Neuroepithelial Tumor (DNET)
  description: >-
    CNS WHO grade 1 glioneuronal tumor defined by the "specific glioneuronal
    element" with columns of oligodendrocyte-like cells in a myxoid matrix and
    "floating neurons". FGFR1 alterations are present in the majority (>75%) of
    cases. Presents with drug-resistant epilepsy from cortical, often temporal,
    lesions.
  subtype_term:
    preferred_term: dysembryoplastic neuroepithelial tumor
    term:
      id: MONDO:0005505
      label: dysembryoplastic neuroepithelial tumor
  evidence:
  - reference: PMID:35018490
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Five tumors were classified as dysembryoplastic neuroepithelial tumor (DNT), 4 as pilocytic astrocytoma (PA) and 3 as rosette-forming glioneuronal tumor (RGNT). FGFR1 mutations were associated with oligodendroglia-like cells"
    explanation: Documents FGFR1 hotspot mutations in DNET and their association with the oligodendrocyte-like cells characteristic of DNET.
- name: Papillary Glioneuronal Tumor
  description: >-
    CNS WHO grade 1 glioneuronal tumor with a pseudopapillary architecture lined by
    GFAP-positive glial cells and interpapillary synaptophysin-positive neuronal
    cells. Characterized molecularly by the SLC44A1::PRKCA fusion. Usually presents
    in young adults with seizures and/or headaches from a circumscribed
    supratentorial mass.
  subtype_term:
    preferred_term: papillary glioneuronal tumor
    term:
      id: MONDO:0016735
      label: papillary glioneuronal tumor
  evidence:
  - reference: PMID:35512827
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "anaplastic ganglioglioma, papillary glioneuronal tumor, rosette-forming glioneuronal tumor, gangliocytoma, and central neurocytoma are less frequent."
    explanation: Identifies papillary glioneuronal tumor as one of the less-frequent glioneuronal tumor subtypes.
- name: Rosette-forming Glioneuronal Tumor
  display_name: Rosette-Forming Glioneuronal Tumor (RGNT)
  description: >-
    CNS WHO grade 1 glioneuronal tumor with neurocytic rosettes and perivascular
    pseudorosettes alongside an astrocytic component, typically arising in the
    posterior fossa / fourth-ventricle region. Driven by FGFR1 hotspot mutations,
    often with PIK3CA, PIK3R1, or NF1 co-alterations. Presents more often with
    headache, ataxia, and hydrocephalus than with epilepsy.
  subtype_term:
    preferred_term: rosette-forming glioneuronal tumor
    term:
      id: MONDO:0016736
      label: rosette-forming glioneuronal tumor of fourth ventricule
  evidence:
  - reference: PMID:35018490
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Five tumors were classified as dysembryoplastic neuroepithelial tumor (DNT), 4 as pilocytic astrocytoma (PA) and 3 as rosette-forming glioneuronal tumor (RGNT)."
    explanation: Documents FGFR1 hotspot mutations identified in rosette-forming glioneuronal tumor cases.
- name: Desmoplastic Infantile Ganglioglioma
  display_name: Desmoplastic Infantile Ganglioglioma (DIG)
  description: >-
    CNS WHO grade 1 infantile glioneuronal tumor with a prominent desmoplastic
    stroma containing astroglial and neuronal/ganglion cell elements. Presents in
    infancy (usually within the first 2 years of life), typically as a large
    superficial cystic/solid mass causing macrocephaly, an enlarging head
    circumference, and signs of raised intracranial pressure.
  subtype_term:
    preferred_term: desmoplastic infantile ganglioglioma
    term:
      id: MONDO:0022965
      label: desmoplastic infantile ganglioglioma
  evidence:
  - reference: PMID:35512827
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "While ganglioglioma, dysembryoplastic neuroepithelial tumor, and desmoplastic infantile tumor are common glioneuronal tumors"
    explanation: Identifies desmoplastic infantile tumor (desmoplastic infantile ganglioglioma) among the glioneuronal tumors.
pathophysiology:
- name: MAPK Pathway Activation
  description: >-
    The initiating and central pathogenic event is a somatic genetic alteration that
    constitutively activates the RAS-RAF-MEK-ERK (MAPK) signaling cascade. In
    ganglioglioma the dominant driver is the BRAF p.V600E missense mutation
    (glutamic acid-to-valine substitution in the kinase domain), while in DNET and
    other entities FGFR1 hotspot mutations (N546K, K656E) predominate; FGFR1
    activation simultaneously stimulates the RAS/RAF/MEK and PI3K-AKT cascades.
    These low-grade glioneuronal tumors are considered developmental neoplasms
    arising from MAPK-activated neural progenitors rather than from environmental
    exposures.
  gene:
    preferred_term: BRAF
    term:
      id: hgnc:1097
      label: BRAF
  biological_processes:
  - preferred_term: MAPK cascade
    term:
      id: GO:0000165
      label: MAPK cascade
    modifier: INCREASED
  - preferred_term: positive regulation of cell proliferation
    term:
      id: GO:0008284
      label: positive regulation of cell population proliferation
    modifier: INCREASED
  - preferred_term: negative regulation of apoptosis
    term:
      id: GO:0043066
      label: negative regulation of apoptotic process
    modifier: INCREASED
  cell_types:
  - preferred_term: neural progenitor cell
    term:
      id: CL:0011020
      label: neural progenitor cell
  evidence:
  - reference: PMID:35018490
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Low-grade gliomas (LGG) and mixed neuronal-glial tumors (MNGT) show frequent MAPK pathway alterations."
    explanation: Establishes that MAPK pathway alterations are the frequent, shared molecular driver of mixed neuronal-glial tumors.
  - reference: PMID:41721014
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The most common mutation was BRAFV600E present in 36.94%, followed by the mutation in FGFR1, reported in 1.18% of cases."
    explanation: Systematic review of 1360 gangliogliomas establishes BRAF V600E as the most common MAPK-activating driver, with FGFR1 next.
  downstream:
  - target: Dual Neuronal-Glial Differentiation
    description: >-
      Constitutive MAPK activation in neural progenitors during development drives
      aberrant proliferation and dual differentiation toward both neuronal and glial
      lineages, producing the characteristic mixed cellular composition.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
- name: Dual Neuronal-Glial Differentiation
  description: >-
    Aberrant differentiation of MAPK-activated neural progenitors yields a neoplasm
    containing both a neoplastic neuronal component (dysmorphic ganglion cells,
    floating neurons, or neurocytic rosettes depending on subtype) and a neoplastic
    glial component (astrocytic GFAP-positive and/or oligodendrocyte-like
    OLIG2-positive cells). This dual lineage is the defining histological feature
    of glioneuronal tumors and distinguishes them from pure gliomas.
  biological_processes:
  - preferred_term: neuron differentiation
    term:
      id: GO:0030182
      label: neuron differentiation
    modifier: ABNORMAL
  - preferred_term: cell fate determination
    term:
      id: GO:0001709
      label: cell fate determination
    modifier: ABNORMAL
  cell_types:
  - preferred_term: neoplastic neuron
    term:
      id: CL:0000540
      label: neuron
  - preferred_term: neoplastic astrocyte
    term:
      id: CL:0000127
      label: astrocyte
  - preferred_term: neoplastic oligodendrocyte-like cell
    term:
      id: CL:0000128
      label: oligodendrocyte
  evidence:
  - reference: PMID:35512827
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Glioneuronal tumors are characterized exclusively by neurocytic elements (neuronal tumors) or a combination of neuronal and glial features (mixed neuronal-glial tumors)."
    explanation: Defines the dual neuronal and glial composition that characterizes mixed neuronal-glial tumors.
  downstream:
  - target: Cortical Low-Grade Neoplasm
    description: >-
      The mixed neuronal-glial proliferation forms a circumscribed, slow-growing
      (CNS WHO grade 1) tumor, typically in the cerebral cortex with a predilection
      for the temporal and frontal lobes.
    causal_link_type: DIRECT
- name: Cortical Low-Grade Neoplasm
  description: >-
    A circumscribed, indolent (most commonly CNS WHO grade 1) neoplasm situated in
    the cerebral cortex, most often the temporal lobe. The cortical/subcortical
    location and intimate relationship with surrounding cortex underlie both the
    typical seizure presentation and the favorable outcome after gross total
    resection.
  locations:
  - preferred_term: cerebral cortex
    term:
      id: UBERON:0000956
      label: cerebral cortex
  - preferred_term: temporal lobe
    term:
      id: UBERON:0001871
      label: temporal lobe
  evidence:
  - reference: PMID:36831464
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Rare glial, neuronal and glioneuronal tumours in adults form a heterogeneous group of rare, primary central nervous system tumours."
    explanation: Establishes glioneuronal tumors as a group of primary CNS (brain) neoplasms.
  downstream:
  - target: Epileptogenic Cortical Disruption
    description: >-
      The cortical tumor, frequently associated with adjacent focal cortical
      dysplasia, disrupts local cortical circuitry and creates an epileptogenic
      zone with high intrinsic epileptogenic potential.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
- name: Epileptogenic Cortical Disruption
  description: >-
    Glioneuronal tumors, particularly ganglioglioma and DNET, are among the most
    common causes of drug-resistant focal epilepsy. The intimate cortical location,
    abnormal neuronal differentiation, and frequent association with focal cortical
    dysplasia generate a highly epileptogenic substrate, such that these tumors have
    been informally termed "epileptomas".
  locations:
  - preferred_term: cerebral cortex
    term:
      id: UBERON:0000956
      label: cerebral cortex
  evidence:
  - reference: PMID:34196984
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Structural brain lesions, including the broad range of malformations of cortical development (MCD) and glioneuronal tumors, are among the most common causes of drug-resistant focal epilepsy."
    explanation: Establishes glioneuronal tumors as a leading structural cause of drug-resistant focal epilepsy via cortical disruption.
  downstream:
  - target: Drug-Resistant Focal Epilepsy
    description: >-
      The epileptogenic cortical substrate manifests clinically as chronic,
      frequently drug-resistant focal seizures, the dominant presenting phenotype
      of these tumors.
    causal_link_type: DIRECT
phenotypes:
- category: Neurologic
  name: Drug-Resistant Focal Epilepsy
  description: >-
    Chronic focal-onset seizures, frequently medically refractory, are the dominant
    clinical presentation of mixed neuronal-glial tumors, especially ganglioglioma
    and DNET. Onset is typically in childhood to young adulthood with a long
    pre-diagnosis history.
  phenotype_term:
    preferred_term: Drug-resistant focal-onset seizure
    term:
      id: HP:0007359
      label: Focal-onset seizure
    temporality: CHRONIC
  evidence:
  - reference: PMID:34196984
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Structural brain lesions, including the broad range of malformations of cortical development (MCD) and glioneuronal tumors, are among the most common causes of drug-resistant focal epilepsy."
    explanation: Documents drug-resistant focal epilepsy as a hallmark phenotype caused by glioneuronal tumors.
  - reference: PMID:35512827
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Most of these tumors occur in young patients and are related to epilepsy."
    explanation: Supports the strong association of glioneuronal tumors with epilepsy and young age of onset.
- category: Neurologic
  name: Seizure
  description: >-
    Seizures, including focal seizures that may secondarily generalize, are present
    in the large majority of patients and are often the initial manifestation.
  phenotype_term:
    preferred_term: Seizure
    term:
      id: HP:0001250
      label: Seizure
  evidence:
  - reference: PMID:35512827
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Most of these tumors occur in young patients and are related to epilepsy."
    explanation: Supports seizures as a characteristic phenotype of glioneuronal tumors.
- category: Neoplasm
  name: CNS Glioneuronal Neoplasm
  description: >-
    The tumor itself is a neuronal/glioneuronal neoplasm of the central nervous
    system, typically cortical and circumscribed.
  phenotype_term:
    preferred_term: Neuronal/glioneuronal neoplasm of the central nervous system
    term:
      id: HP:0025170
      label: Neuronal/glioneuronal neoplasm of the central nervous system
  evidence:
  - reference: PMID:35512827
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Glioneuronal tumors are characterized exclusively by neurocytic elements (neuronal tumors) or a combination of neuronal and glial features (mixed neuronal-glial tumors)."
    explanation: Defines the entity as a CNS glioneuronal neoplasm.
- category: Neurologic
  name: Headache
  description: >-
    Headache occurs less commonly than seizures and is more typical of tumors
    causing mass effect or hydrocephalus, such as posterior fossa RGNT or
    intraventricular neurocytoma.
  phenotype_term:
    preferred_term: Headache
    term:
      id: HP:0002315
      label: Headache
- category: Neurologic
  name: Hydrocephalus
  description: >-
    Hydrocephalus is seen particularly with intraventricular tumors (e.g., central
    neurocytoma) and with leptomeningeal spread, reflecting obstruction of CSF flow.
  phenotype_term:
    preferred_term: Hydrocephalus
    term:
      id: HP:0000238
      label: Hydrocephalus
- category: Neurologic
  name: Macrocephaly
  subtype: Desmoplastic Infantile Ganglioglioma
  description: >-
    Macrocephaly with an enlarging head circumference is characteristic of
    desmoplastic infantile ganglioglioma, which presents in infancy with a large
    superficial mass.
  phenotype_term:
    preferred_term: Macrocephaly
    term:
      id: HP:0000256
      label: Macrocephaly
genetic:
- name: BRAF
  notes: >-
    BRAF p.V600E is the single most common somatic alteration in mixed
    neuronal-glial tumors, found in roughly 36.9% of gangliogliomas in a systematic
    review of 1360 cases. The substitution causes constitutive activation of the
    BRAF serine/threonine kinase and the downstream MAPK/ERK pathway. BRAF V600E is
    also the most actionable therapeutic target in this tumor group.
  gene_term:
    preferred_term: BRAF
    term:
      id: hgnc:1097
      label: BRAF
  association: Most common somatic driver mutation (p.V600E)
  relationship_type: SOMATIC_DRIVER
  variant_origin: SOMATIC
  evidence:
  - reference: PMID:41721014
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The most common mutation was BRAFV600E present in 36.94%, followed by the mutation in FGFR1, reported in 1.18% of cases."
    explanation: Quantifies BRAF V600E as the most frequent somatic alteration in gangliogliomas.
- name: FGFR1
  notes: >-
    FGFR1 hotspot alterations (N546K, K656E) are the dominant driver in DNET (>75%)
    and recur in rosette-forming glioneuronal tumor and other entities, while being
    rare in ganglioglioma. FGFR1 is the fifth most prevalent alteration across
    low-grade glioma / mixed neuronal-glial tumors, and FGFR1 sequencing of
    driver-unknown low-grade brain tumors can yield up to 12% N546/K656 mutant cases.
  gene_term:
    preferred_term: FGFR1
    term:
      id: hgnc:3688
      label: FGFR1
  association: Dominant somatic driver in DNET and RGNT; rare in ganglioglioma
  relationship_type: SOMATIC_DRIVER
  variant_origin: SOMATIC
  evidence:
  - reference: PMID:35018490
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "FGFR1 hotspot mutations are the fifth most prevailing alteration in LGG/MNGT. Performing FGFR1 sequencing analysis in driver-unknown low-grade brain tumors could yield up to 12% FGFR1 N546/K656 mutant cases."
    explanation: Establishes FGFR1 hotspot mutations as a recurrent driver of mixed neuronal-glial tumors.
treatments:
- name: Surgical Resection
  description: >-
    Gross total surgical resection is the cornerstone of treatment and is considered
    curative for most CNS WHO grade 1 glioneuronal tumors. For epilepsy-associated
    tumors, extended resection that includes the epileptogenic zone improves
    seizure-free outcomes.
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: MAXO:0000004
      label: surgical procedure
  target_mechanisms:
  - target: Cortical Low-Grade Neoplasm
    treatment_effect: BYPASSES
    description: >-
      Resection physically removes the cortical tumor and epileptogenic substrate,
      addressing both the neoplasm and the seizures.
- name: BRAF/MEK Inhibitor Targeted Therapy
  description: >-
    For BRAF p.V600E-mutant tumors that are progressive, recurrent, or unresectable,
    combined BRAF and MEK inhibition (e.g., dabrafenib plus trametinib) is the
    preferred targeted approach; BRAF V600E is the only molecular target of proven
    clinical benefit in adult gliomas/glioneuronal tumors per EANO. In a
    multi-institutional series of BRAF-mutant pediatric high-grade gliomas
    (including anaplastic gangliogliomas) treated upfront, 3-year progression-free
    and overall survival were 65% and 82%.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
  therapeutic_modality: SMALL_MOLECULE
  target_mechanisms:
  - target: MAPK Pathway Activation
    treatment_effect: INHIBITS
    description: >-
      BRAF and MEK inhibitors block constitutive RAS-RAF-MEK-ERK signaling driven
      by the BRAF V600E mutation.
  evidence:
  - reference: PMID:39387386
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "From all targets reviewed, only testing for BRAF V600E mutations was of proven clinical benefit"
    explanation: EANO guideline update establishes BRAF V600E as the only target of proven clinical benefit, justifying BRAF-directed therapy.
  - reference: PMID:35397478
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "three-year progression-free and overall survival for the cohort were 65% and 82%, respectively, and superior to a historical control cohort of BRAF-mutant pHGG patients treated with conventional therapies."
    explanation: Demonstrates efficacy of upfront BRAF/MEK targeted therapy in BRAF-mutant tumors including anaplastic ganglioglioma.
- name: Radiation Therapy
  description: >-
    Radiotherapy is reserved for subtotally resected aggressive tumors, tumors in
    eloquent areas, or recurrent disease, and is used cautiously in young children
    because of long-term cognitive sequelae.
  treatment_term:
    preferred_term: radiation therapy
    term:
      id: MAXO:0000014
      label: radiation therapy
diagnosis:
- name: MRI with Genotype Correlation
  description: >-
    MRI is the cornerstone of diagnosis. Genotype-relevant imaging patterns have
    been described: BRAF V600E tumors show indistinct borders with iso-T1 and high
    T2 signal without diffuse mass effect (93.8% sensitivity, 100% specificity),
    whereas FGFR1-mutant tumors show sharp borders and very high T2 signal with a
    diffuse mass effect (100% sensitivity and specificity).
  evidence:
  - reference: PMID:39081340
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Group 1 had indistinct borders and iso T1-weighted and slightly high or high T2-weighted signal intensities without a diffuse mass effect, associated with 93.8% sensitivity and 100% specificity to BRAF V600E mutations; Group 2 exhibited sharp borders and very or slightly low T1-weighted and very high T2-weighted signal intensities with a diffuse mass effect and 100% sensitivity and specificity for FGFR1 mutations"
    explanation: Documents genotype-relevant neuroimaging features distinguishing BRAF V600E from FGFR1-mutant low-grade epilepsy-associated tumors.
clinical_trials:
- name: NCT02684058
  phase: PHASE_II
  status: COMPLETED
  description: >-
    Dabrafenib plus trametinib in pediatric patients with BRAF V600 mutation-positive
    low-grade glioma or relapsed high-grade glioma.
  target_phenotypes:
  - preferred_term: Seizure
    term:
      id: HP:0001250
      label: Seizure
  evidence:
  - reference: clinicaltrials:NCT02684058
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The purpose of this study was to investigate the activity of dabrafenib in combination with trametinib in children and adolescent patients with BRAF V600 mutation positive low grade glioma (LGG) or relapsed or refractory high grade glioma (HGG)"
    explanation: Trial evaluating BRAF/MEK inhibition in BRAF V600-mutant pediatric CNS tumors relevant to BRAF-mutant glioneuronal tumors.
epidemiology:
- name: Incidence and Demographics
  description: >-
    Mixed neuronal-glial tumors are rare, representing less than 2% of all primary
    CNS tumors, and predominantly affect children, adolescents, and young adults.
    Most arise from somatic, non-hereditary alterations with no Mendelian
    inheritance pattern.

📚

References & Deep Research

References

2

PMID:36831464

Rare Neuronal, Glial and Glioneuronal Tumours in Adults.

No top-level findings curated for this source.

PMID:35218102

The 2021 WHO Classification of Tumors of the Central Nervous System: An update on pediatric low-grade gliomas and glioneuronal tumors.

No top-level findings curated for this source.

Deep Research

1

Falcon ▸

1. Disease Information

Edison Scientific Literature 44 citations 2026-06-30T10:08:55.042047

1. Disease Information

Overview

Mixed neuronal-glial tumors (also termed glioneuronal tumors) are a heterogeneous group of rare primary central nervous system (CNS) neoplasms composed of both neuronal and glial cell populations in varying proportions (crainic2023rareneuronalglial pages 1-2). They represent less than 2% of all primary CNS tumors and predominantly affect children and young adults, with a strong predilection for the temporal and frontal lobes and a frequent association with epilepsy (crainic2023rareneuronalglial pages 1-2, vaz2022uncommonglioneuronaltumors pages 1-4). The 2021 WHO Classification of Tumors of the Central Nervous System (CNS5, 5th edition) reorganized these tumors into one of six families: "Glioneuronal and neuronal tumors," alongside closely related entities in the "Pediatric-type diffuse low-grade gliomas" and "Circumscribed astrocytic gliomas" families (bale2022the2021who pages 1-2, bale2022the2021who pages 2-3).

Key Identifiers

MONDO ID: MONDO:0016729 (mixed neuronal-glial tumor) (OpenTargets Search: mixed neuronal-glial tumor,ganglioglioma,glioneuronal tumor)
ICD-O-3 codes: Multiple codes apply depending on subtype (e.g., 9505/1 for ganglioglioma, 9413/0 for DNET)
MeSH: Glioneuronal tumors / Neuronal and mixed neuronal-glial tumors
Common Synonyms: Glioneuronal tumor, mixed glioneuronal neoplasm, neuronal-glial tumor

Subtypes per WHO 2021 Classification

The following table provides a comprehensive overview of subtypes, grades, molecular features, histopathology, age of onset, and clinical presentation:

Tumor type	WHO 2021 status / grade	Key molecular alterations	Characteristic histology / IHC markers	Typical age of onset	Common clinical presentation
Ganglioglioma	CNS WHO grade 1	BRAF p.V600E most common; less often FGFR1, KRAS, NF1, H3-3A/H3 K27M, RAF1 alterations; MAPK-pathway activation (pereira2026molecularfeaturesin pages 1-2, pereira2026molecularfeaturesin pages 2-4, crainic2023rareneuronalglial pages 6-8)	Dysmorphic neuronal cells with neoplastic glial component; eosinophilic granular bodies, lymphocytic infiltrates, CD34+ ramified cells; neuronal cells synaptophysin+/chromogranin A+; glial cells GFAP+/OLIG2+; Ki-67 usually <3% (crainic2023rareneuronalglial pages 6-8, vaz2022uncommonglioneuronaltumors pages 1-4)	Usually childhood to young adulthood (vaz2022uncommonglioneuronaltumors pages 1-4, crainic2023rareneuronalglial pages 1-2)	Long-standing focal epilepsy/seizures, often temporal lobe; headaches less common (crainic2023rareneuronalglial pages 1-2, vaz2022uncommonglioneuronaltumors pages 1-4)
Dysembryoplastic neuroepithelial tumor (DNET)	CNS WHO grade 1	FGFR1 alterations in >75%; BRAF p.V600E in <1/3; MAPK-pathway altered (crainic2023rareneuronalglial pages 6-8, kobow2021moleculardiagnosticsin pages 2-4)	Specific glioneuronal element with columns of oligodendroglia-like cells in myxoid matrix and “floating neurons”; Olig2+ oligodendroglia-like cells; floating neurons NeuN+/synaptophysin+ (crainic2023rareneuronalglial pages 6-8)	Usually children/adolescents and young adults (crainic2023rareneuronalglial pages 1-2)	Drug-resistant epilepsy, often cortical/temporal lesions (crainic2023rareneuronalglial pages 1-2, xie2023lowgradeepilepsyassociatedneuroepithelial pages 2-3)
Papillary glioneuronal tumor	CNS WHO grade 1	SLC44A1::PRKCA fusion characteristic; occasional PDGFRA alterations reported (crainic2023rareneuronalglial pages 4-5, vaz2022uncommonglioneuronaltumors pages 4-6)	Pseudopapillary / papillary architecture with GFAP+/S100+ glial lining cells and synaptophysin+/neuronal nuclear protein+ interpapillary neuronal elements; OLIG2+ oligodendrocyte-like cells may be present (vaz2022uncommonglioneuronaltumors pages 4-6)	Mostly young adults (crainic2023rareneuronalglial pages 4-5)	Seizures and/or headaches from circumscribed supratentorial mass (crainic2023rareneuronalglial pages 4-5, crainic2023rareneuronalglial pages 1-2)
Rosette-forming glioneuronal tumor (RGNT)	CNS WHO grade 1	FGFR1 hotspot mutations, often with PIK3CA, PIK3R1, or NF1 co-alterations (crainic2023rareneuronalglial pages 4-5, vaz2022uncommonglioneuronaltumors pages 6-7)	Neurocytic rosettes and perivascular pseudorosettes with astrocytic component; neuronal cells synaptophysin+/MAP2+/NSE+; glial cells GFAP+/OLIG2+/S100+ (vaz2022uncommonglioneuronaltumors pages 6-7)	Typically children/young adults (vaz2022uncommonglioneuronaltumors pages 1-4, crainic2023rareneuronalglial pages 4-5)	Headache, ataxia, hydrocephalus, posterior fossa / fourth-ventricle symptoms rather than epilepsy (vaz2022uncommonglioneuronaltumors pages 6-7, crainic2023rareneuronalglial pages 4-5)
Diffuse leptomeningeal glioneuronal tumor (DLGNT)	CNS WHO grade 1 in WHO 2021; methylation subclasses MC-1 and MC-2 described (vaz2022uncommonglioneuronaltumors pages 6-7, singh2023currentstatusof pages 3-4)	Frequently KIAA1549::BRAF fusion; also 1p loss and MAPK-pathway alterations; molecular subclassing by methylation clinically relevant (vaz2022uncommonglioneuronaltumors pages 6-7, singh2023currentstatusof pages 3-4, bent2025updatedeanoguideline pages 3-4)	Oligodendroglial-like cells in leptomeningeal/desmoplastic or myxoid background; OLIG2+, S100+, MAP2+ in oligodendroglial cells, GFAP+ astrocytic component (vaz2022uncommonglioneuronaltumors pages 6-7)	Mainly pediatric, but can occur across ages (singh2023currentstatusof pages 3-4, rio2024newcnstumor pages 2-4)	Signs of diffuse leptomeningeal disease: hydrocephalus, cranial/spinal symptoms, multifocal neurologic deficits; epilepsy less typical (vaz2022uncommonglioneuronaltumors pages 6-7)
Myxoid glioneuronal tumor (MGT/MGNT)	CNS WHO grade 1	Recurrent PDGFRA p.K385 mutation; DNT-like methylation profile (bale2022the2021who pages 8-9, capper2023eanoguidelineon pages 11-12)	Oligodendrocyte-like cells in prominent myxoid/mucin-rich stroma with floating neurons and sometimes neurocytic rosettes; strong MAP2/synaptophysin in neuronal component, often GFAP-negative (bale2022the2021who pages 5-6, vaz2022uncommonglioneuronaltumors pages 6-7, bale2022the2021who pages 8-9)	Usually children and young adults (bale2022the2021who pages 8-9)	Seizures or headaches; often septum pellucidum / periventricular lesion discovered on imaging (bale2022the2021who pages 8-9, rio2024newcnstumor pages 2-4)
Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC)	Provisional new type in WHO 2021 glioneuronal/neuronal family	Distinct methylation class; recurrent monosomy 14 / chromosome 14 methylome abnormality (bale2022the2021who pages 1-2, xie2023lowgradeepilepsyassociatedneuroepithelial pages 2-3, bale2022the2021who pages 8-9)	Diffuse tumor with oligodendroglioma-like perinuclear halos and clustered nuclei; synaptophysin+/NeuN+/MAP2+/Olig2+, usually GFAP− or limited GFAP (crainic2023rareneuronalglial pages 5-6, bale2022the2021who pages 3-5)	Predominantly pediatric / young patients (bale2022the2021who pages 1-2, xie2023lowgradeepilepsyassociatedneuroepithelial pages 2-3)	Seizures and focal neurologic symptoms depending on cortical location (bale2022the2021who pages 3-5, xie2023lowgradeepilepsyassociatedneuroepithelial pages 2-3)
Desmoplastic infantile ganglioglioma (DIG)	CNS WHO grade 1	Molecular drivers less consistently defined than other entities; belongs to infantile glioneuronal spectrum in WHO 2021 (vaz2022uncommonglioneuronaltumors pages 1-4, rio2024newcnstumor pages 2-4)	Desmoplastic stroma with astroglial and neuronal/ganglion cell elements; glial cells GFAP+, neuronal cells synaptophysin+ (vaz2022uncommonglioneuronaltumors pages 1-4, rio2024newcnstumor pages 2-4)	Infancy, usually within first 2 years of life (vaz2022uncommonglioneuronaltumors pages 1-4)	Macrocephaly, enlarging head circumference, seizures, signs of raised intracranial pressure from large superficial cystic/solid mass (vaz2022uncommonglioneuronaltumors pages 1-4, rio2024newcnstumor pages 2-4)
Polymorphous low-grade neuroepithelial tumor of the young (PLNTY)	Pediatric-type diffuse low-grade glioma in WHO 2021 (not in glioneuronal family, but overlaps clinically/pathologically with LEATs) (bale2022the2021who pages 1-2, rio2024newcnstumor pages 2-4)	MAPK-pathway altered; BRAF p.V600E, FGFR2/FGFR3 fusions and related FGFR-family alterations (singh2023currentstatusof pages 3-4, bale2022the2021who pages 3-5, bale2022the2021who pages 8-9)	Oligodendroglioma-like / polymorphous infiltrative tumor; strong CD34 expression; strong MAP2 and synaptophysin, mostly GFAP-negative; may show perivascular pseudorosettes (bale2022the2021who pages 3-5, bale2022the2021who pages 8-9)	Children, adolescents, young adults (bale2022the2021who pages 1-2, bale2022the2021who pages 8-9)	Epileptogenic cortical tumor with chronic focal seizures (singh2023currentstatusof pages 3-4, bale2022the2021who pages 8-9)
Multinodular and vacuolating neuronal tumor (MVNT)	CNS WHO grade 1	MAPK-pathway alterations reported; recognized as new WHO 2021 neuronal/glioneuronal-type entity (bale2022the2021who pages 1-2, xie2023lowgradeepilepsyassociatedneuroepithelial pages 2-3)	Multinodular lesion composed of vacuolated neuronal cells; HuC/HuD+, OLIG2+, α-internexin+, weak/negative synaptophysin and neurofilament in some cells (vaz2022uncommonglioneuronaltumors pages 8-9, bale2022the2021who pages 5-6)	Often adults, but can occur across a wide age range (bale2022the2021who pages 5-6, rio2024newcnstumor pages 2-4)	Often incidental; may present with seizures or headaches (bale2022the2021who pages 5-6, vaz2022uncommonglioneuronaltumors pages 8-9)
Anaplastic ganglioglioma	CNS WHO grade 3	May harbor BRAF p.V600E and occasionally H3 alterations; MAPK-driven biology in subset (vaz2022uncommonglioneuronaltumors pages 1-4, vaz2022uncommonglioneuronaltumors pages 4-6)	Dysplastic neuronal cells plus anaplastic glial component, increased cellularity, pleomorphism, frequent mitoses, microvascular proliferation, necrosis; GFAP+/synaptophysin+/CD34+ pattern retained in components (vaz2022uncommonglioneuronaltumors pages 1-4, vaz2022uncommonglioneuronaltumors pages 4-6)	Children to adults (vaz2022uncommonglioneuronaltumors pages 1-4, crainic2023rareneuronalglial pages 6-8)	Seizures, progressive focal deficits, mass effect; more aggressive course than grade 1 ganglioglioma (crainic2023rareneuronalglial pages 6-8, vaz2022uncommonglioneuronaltumors pages 1-4)
Central neurocytoma	CNS WHO grade 2	No single pathognomonic alteration routinely used in WHO; molecular heterogeneity reported (vaz2022uncommonglioneuronaltumors pages 8-9, rio2024newcnstumor pages 2-4)	Uniform round neurocytic cells with scant cytoplasm and neurocytic rosettes; synaptophysin+ and neuron-specific enolase+; OLIG2− (vaz2022uncommonglioneuronaltumors pages 8-9)	Young adults (median around 30 years) (crainic2023rareneuronalglial pages 4-5)	Intraventricular mass causing headache, hydrocephalus, visual symptoms; seizures less common (crainic2023rareneuronalglial pages 4-5, vaz2022uncommonglioneuronaltumors pages 8-9)
Extraventricular neurocytoma	CNS WHO grade 2	FGFR1::TACC1 fusion in about two-thirds in one series/reviewed cohort (crainic2023rareneuronalglial pages 4-5)	Neurocytic tumor outside ventricles; synaptophysin+ neuronal phenotype, similar to central neurocytoma but extraventricular location (crainic2023rareneuronalglial pages 4-5, rio2024newcnstumor pages 2-4)	Young adults (median around 30 years) (crainic2023rareneuronalglial pages 4-5)	Seizures and headaches are common (crainic2023rareneuronalglial pages 4-5)

Table: This table summarizes major mixed neuronal-glial and closely related neuroepithelial tumor subtypes relevant to the WHO 2021 CNS classification, with practical emphasis on grade, molecular drivers, pathology, age, and presentation. It is useful as a quick reference for disease characterization and knowledge-base curation.

2. Etiology

Disease Causal Factors

Mixed neuronal-glial tumors are primarily driven by somatic genetic alterations, particularly those activating the mitogen-activated protein kinase (MAPK) signaling pathway. Gene expression studies have identified alterations in the RAS–RAF–MAPK and PI3K–AKT–mTOR signaling pathways, which affect cell proliferation, differentiation, autophagy, protein synthesis, and cell survival (kobow2021moleculardiagnosticsin pages 2-4). Experimental evidence demonstrates that BRAF V600E mutations in neural progenitors during embryonic development can reproduce ganglioglioma histopathological features and lead to epileptic seizures (kobow2021moleculardiagnosticsin pages 2-4). The tumors are generally considered developmental or hamartomatous neoplasms arising from aberrant neurodevelopment rather than from acquired environmental exposures.

Genetic Risk Factors

BRAF V600E: The most common somatic alteration, present in approximately 36.94% of gangliogliomas (528 of 1360 cases in a systematic review of 43 studies) (pereira2026molecularfeaturesin pages 1-2, pereira2026molecularfeaturesin pages 2-4). This glutamic acid-to-valine substitution causes constitutive activation of the serine/threonine kinase domain, promoting oncogenic transformation (pereira2026molecularfeaturesin pages 4-5).
FGFR1: FGFR1 hotspot mutations (N546K and K656E) are the fifth most prevalent alteration in LGG/MNGT; among driver-unknown samples, up to 12% harbor these mutations (engelhardt2022frequentfgfr1hotspot pages 1-2). FGFR1 alterations are present in >75% of DNETs (crainic2023rareneuronalglial pages 6-8).
NF1/PTPN11/KRAS: A subgroup of gangliogliomas with PTPN11/KRAS/NF1 alterations has been identified, showing adverse clinical outcomes and atypical histopathological features, with only 38% achieving Engel I seizure outcome compared to 85% for BRAF V600E-only gangliogliomas (pereira2026molecularfeaturesin pages 8-9).
Neurofibromatosis type 1 (NF1): Germline NF1 mutations predispose to various glioneuronal tumors.

Environmental and Lifestyle Risk Factors

No specific environmental or lifestyle risk factors have been consistently identified for mixed neuronal-glial tumors. These tumors are not associated with known carcinogen exposures, ionizing radiation, or infectious agents based on current evidence. The primary etiologic mechanism appears to be somatic genetic alteration during neural development.

Gene-Environment Interactions

No well-established gene-environment interactions have been documented for this tumor group. The predominantly somatic, developmental nature of the underlying genetic alterations suggests limited environmental modulation.

3. Phenotypes

Primary Phenotypes

Seizures / Epilepsy (HP:0001250) - Type: Symptom (neurological) - Characteristics: Drug-resistant focal epilepsy is the hallmark presentation; seizures are present in the vast majority of cases, often with onset at a young age and a long-term history (crainic2023rareneuronalglial pages 1-2, vaz2022uncommonglioneuronaltumors pages 1-4). Ganglioglioma and DNET have been informally termed "epileptomas" due to their extremely high epileptogenic potential (crainic2023rareneuronalglial pages 1-2). - Onset: Childhood to young adulthood - Severity: Often medically refractory (drug-resistant) - Frequency: >80% of gangliogliomas and DNETs

Headache (HP:0002315) - Type: Symptom - Characteristics: Less common than seizures; may present in tumors causing mass effect or hydrocephalus - Frequency: Variable, more common in posterior fossa tumors (RGNT) and central neurocytoma

Focal neurological deficits (HP:0007340) - Type: Clinical sign - Characteristics: Depend on tumor location; may include motor weakness, sensory changes, visual field deficits - Onset: Variable; more common in aggressive subtypes (anaplastic ganglioglioma)

Hydrocephalus (HP:0000238) - Type: Clinical sign - Characteristics: Seen particularly with intraventricular tumors (central neurocytoma) and leptomeningeal spread (DLGNT)

Macrocephaly (HP:0000256) - Type: Physical manifestation - Characteristics: Particularly relevant to desmoplastic infantile ganglioglioma presenting in infancy

Quality of Life Impact: Chronic epilepsy significantly impairs quality of life, including cognitive development in children, educational achievement, employment, driving ability, and psychosocial functioning. Successful surgical resection with seizure freedom provides the greatest quality-of-life benefit.

4. Genetic/Molecular Information

Causal Genes and Pathogenic Variants

OpenTargets disease-target association analysis identified 8 key targets for mixed neuronal-glial tumor (MONDO:0016729), with PTEN (score 0.66), BRAF (score 0.63), FGFR1 (score 0.48), H3-3A (score 0.42), NTRK3 (score 0.38), IDH1 (score 0.37), ETV6 (score 0.37), and MUTYH (score 0.34) as the top associations (OpenTargets Search: mixed neuronal-glial tumor,ganglioglioma,glioneuronal tumor).

BRAF (HGNC:1097; ENSG00000157764): - V600E missense mutation: most frequent alteration in gangliogliomas at 36.32–36.94% (pereira2026molecularfeaturesin pages 1-2, pereira2026molecularfeaturesin pages 2-4) - Additional variants: duplications, in-frame insertions, and fusions including KIAA1549::BRAF (pereira2026molecularfeaturesin pages 2-4) - Somatic origin; constitutive activation of MAPK/ERK pathway - ClinVar: RCV000515781 for BRAF-mixed neuronal-glial tumor association

FGFR1 (HGNC:3688; ENSG00000077782): - Hotspot mutations N546K and K656E; present in 1.18% of gangliogliomas but dominant in DNETs (>75%) (engelhardt2022frequentfgfr1hotspot pages 1-2, pereira2026molecularfeaturesin pages 1-2, crainic2023rareneuronalglial pages 6-8) - FGFR activation phosphorylates kinase domains to activate Ras/Raf/MEK and PI3K-Akt pathways (engelhardt2022frequentfgfr1hotspot pages 1-2)

FGFR1::TACC1 fusion: Reported in approximately two-thirds of extraventricular neurocytomas (crainic2023rareneuronalglial pages 4-5)

SLC44A1::PRKCA fusion: Characteristic of papillary glioneuronal tumor (crainic2023rareneuronalglial pages 4-5, crainic2023rareneuronalglial pages 5-6, vaz2022uncommonglioneuronaltumors pages 4-6)

PDGFRA p.K385 mutation: Defining alteration for myxoid glioneuronal tumor (capper2023eanoguidelineon pages 11-12, bale2022the2021who pages 8-9)

Epigenetic Information

DNA methylation profiling has emerged as a critical diagnostic tool for classifying glioneuronal tumors. The DKFZ/Heidelberg CNS tumor classifier uses machine learning-based methylation analysis to distinguish tumor subtypes, and methylation classification confirmed or refined morphological diagnoses in a significant proportion of cases (singh2023currentstatusof pages 3-4). DLGNT shows two molecular subclasses (MC-1 and MC-2) based on distinct methylation profiles with different age presentations and survival outcomes (singh2023currentstatusof pages 3-4). DGONC is defined by a distinct methylation class associated with monosomy 14 (bale2022the2021who pages 1-2, xie2023lowgradeepilepsyassociatedneuroepithelial pages 2-3, bale2022the2021who pages 8-9).

Chromosomal Abnormalities

1p deletion: Characteristic of DLGNT
Monosomy 14: Defining feature of DGONC (bale2022the2021who pages 1-2, bale2022the2021who pages 8-9)
Chromosome 12 gains, NF1 CNV losses: Identified in PTPN11-altered gangliogliomas (pereira2026molecularfeaturesin pages 8-9)

5. Environmental Information

No specific environmental toxins, radiation exposures, or lifestyle factors have been established as causative or contributory for mixed neuronal-glial tumors based on current evidence. No infectious agents have been implicated in the pathogenesis of these tumors.

6. Mechanism / Pathophysiology

Molecular Pathways

The central pathogenic mechanism involves constitutive activation of the RAS–RAF–MEK–ERK (MAPK) signaling cascade (kobow2021moleculardiagnosticsin pages 2-4, pereira2026molecularfeaturesin pages 4-5). BRAF V600E mutations cause constitutive kinase activation, leading to uncontrolled cell proliferation and oncogenic transformation. BRAF inhibitors work by selectively binding to V600E-mutated B-Raf proteins and preventing MEK activation (pereira2026molecularfeaturesin pages 4-5).

The PI3K–AKT–mTOR pathway also plays a role, particularly through co-mutations in PIK3CA and PIK3R1 observed in rosette-forming glioneuronal tumors (crainic2023rareneuronalglial pages 4-5). FGFR1 activation simultaneously stimulates both Ras/Raf/MEK and PI3K-Akt cascades (engelhardt2022frequentfgfr1hotspot pages 1-2).

Relevant GO terms: - GO:0000165 (MAPK cascade) - GO:0043066 (negative regulation of apoptotic process) - GO:0008284 (positive regulation of cell population proliferation) - GO:0048015 (phosphatidylinositol-mediated signaling)

Cellular Processes

Cell proliferation driven by constitutive MAPK activation
Aberrant neural progenitor differentiation during development
Epileptogenesis through cortical involvement and association with focal cortical dysplasia (FCD) (kobow2021moleculardiagnosticsin pages 2-4)

Relevant CL terms: - CL:0000540 (neuron) - CL:0000127 (astrocyte) - CL:0000128 (oligodendrocyte) - CL:0002319 (neural cell)

Causal Chain

Somatic mutation (e.g., BRAF V600E) in neural progenitor during embryonic development → constitutive MAPK/ERK pathway activation → aberrant cell proliferation and differentiation → formation of mixed neuronal-glial neoplasm in cortex → cortical disruption and epileptogenic zone formation → drug-resistant focal epilepsy (kobow2021moleculardiagnosticsin pages 2-4).

7. Anatomical Structures Affected

Primary Organs

Brain (UBERON:0000955): Primary site of involvement
Cerebral cortex (UBERON:0000956): Most common location, especially temporal lobe
Temporal lobe (UBERON:0001871): Predilection site for ganglioglioma and DNET (vaz2022uncommonglioneuronaltumors pages 1-4)
Fourth ventricle / Posterior fossa: Common site for RGNT (crainic2023rareneuronalglial pages 4-5)
Septum pellucidum / Lateral ventricle: Characteristic for myxoid glioneuronal tumor (bale2022the2021who pages 8-9)
Leptomeninges (UBERON:0000016): Involved in DLGNT
Spinal cord (UBERON:0002240): Can be involved in DLGNT and rare glioneuronal tumors

Tissue and Cell Level

Neuronal cells: Dysmorphic ganglion cells (ganglioglioma), floating neurons (DNET), neurocytic rosettes (RGNT)
Glial cells: Astrocytic (GFAP+) and oligodendroglial (OLIG2+) components
Progenitor cells: CD34+ ramified cells characteristically present (vaz2022uncommonglioneuronaltumors pages 1-4)

8. Temporal Development

Onset

Typical age: Predominantly childhood to young adulthood (crainic2023rareneuronalglial pages 1-2, vaz2022uncommonglioneuronaltumors pages 1-4)
Desmoplastic infantile ganglioglioma: Presents in infancy, usually first 2 years of life
Onset pattern: Typically insidious, with chronic seizures developing over months to years before diagnosis

Progression

Most subtypes (WHO grade 1): Slow-growing, indolent biological behavior with long-term seizure history (crainic2023rareneuronalglial pages 1-2)
Anaplastic ganglioglioma (WHO grade 3): More aggressive course with potential for rapid progression (crainic2023rareneuronalglial pages 6-8, vaz2022uncommonglioneuronaltumors pages 1-4)
Disease course: Generally stable or slowly progressive; recurrence possible, particularly with subtotal resection

9. Inheritance and Population

Epidemiology

According to the CBTRUS Statistical Report (2014–2018), neuronal and mixed neuronal-glial tumors had an annual average of 58 cases and 5-year total of 290 cases in the United States, with an age-adjusted incidence rate (AAAIR) of 0.05 per 100,000 population (95% CI: 0.04–0.06) (ostrom2021cbtrusstatisticalreport pages 50-51). These tumors represent less than 2% of all primary CNS tumors (crainic2023rareneuronalglial pages 1-2).

Population Demographics

Age distribution: Predominantly affects children, adolescents, and young adults
Sex ratio: Most subtypes show no strong sex predilection, though some series report slight male predominance
Geographic distribution: No documented geographic clustering; reported worldwide
Inheritance: Almost exclusively somatic (non-hereditary) mutations. No Mendelian inheritance pattern. Rare association with NF1 (autosomal dominant predisposition syndrome).

10. Diagnostics

Clinical Tests

Imaging (MAXO:0000387 - imaging study): - MRI is the cornerstone of neuroimaging. Gangliogliomas typically appear as cortical/subcortical cystic-solid lesions with enhancement. DNETs often show cortical "bubbly" T2-hyperintense lesions without mass effect. Genotype-neuroimaging correlations have been identified: BRAF V600E tumors show indistinct borders with iso-T1/high-T2 signal (93.8% sensitivity, 100% specificity), while FGFR1-mutant tumors show sharp borders with very high T2 signal and diffuse mass effect (100% sensitivity and specificity) (iijima2024genotyperelevantneuroimagingfeatures pages 9-9).

Histopathology and Immunohistochemistry: - Ganglioglioma: Synaptophysin+/Chromogranin A+ neuronal cells, GFAP+/OLIG2+ glial cells, eosinophilic granular bodies, CD34+ stellate cells, Ki67 <3% (crainic2023rareneuronalglial pages 6-8, vaz2022uncommonglioneuronaltumors pages 1-4) - DNET: "Floating neurons" in myxoid matrix, NeuN+/synaptophysin+ neurons, Olig2+ oligodendroglia-like cells (crainic2023rareneuronalglial pages 6-8) - RGNT: Synaptophysin+/MAP2+/NSE+ neurocytic rosettes, GFAP+/OLIG2+/S100+ glial component (vaz2022uncommonglioneuronaltumors pages 6-7)

Molecular/Genetic Testing: The EANO guideline recommends next-generation sequencing (NGS) panel diagnostics rather than sequential target-specific testing, given the low prevalence (<5%) of individual targets in CNS tumors (capper2023eanoguidelineon pages 3-4). DNA methylation profiling using the DKFZ/Heidelberg classifier is increasingly essential for accurate subtyping (singh2023currentstatusof pages 3-4). The 2023 EANO molecular diagnostic tools guideline systematically reviews methods including NGS for DNA and RNA, methylome profiling, and immunohistochemistry for marker assessment (capper2023eanoguidelineon pages 3-4).

Differential Diagnosis

Key differential diagnoses include: pilocytic astrocytoma, oligodendroglioma (IDH-mutant, 1p/19q-codeleted), pleomorphic xanthoastrocytoma, angiocentric glioma, focal cortical dysplasia, and diffuse low-grade glioma (vaz2022uncommonglioneuronaltumors pages 4-6, bale2022the2021who pages 3-5).

11. Outcome/Prognosis

Survival and Mortality

Ganglioglioma (WHO grade 1): 10-year survival exceeds 80% with complete surgical resection (crainic2023rareneuronalglial pages 6-8). Gross total resection (GTR) improves both overall survival and seizure control compared to subtotal resection (STR) (crainic2023rareneuronalglial pages 6-8).
Ganglioglioma with PTPN11/KRAS/NF1 alterations: Significantly worse seizure outcomes (38% Engel I) compared to BRAF V600E-only gangliogliomas (85% Engel I), suggesting a clinically relevant adverse subgroup (pereira2026molecularfeaturesin pages 8-9).
DLGNT: Prognosis varies by methylation subclass; MC-1 and MC-2 have different survival outcomes (singh2023currentstatusof pages 3-4).
Anaplastic ganglioglioma (WHO grade 3): More aggressive clinical course with shorter survival.

Prognostic Factors

Extent of surgical resection (GTR vs. STR)
Tumor location (temporal lobe more favorable than infratentorial) (crainic2023rareneuronalglial pages 6-8)
Molecular subgroup (BRAF V600E-only more favorable; PTPN11/KRAS/NF1 subgroup worse) (pereira2026molecularfeaturesin pages 8-9)
Ki67/MIB1 proliferation index (>2% associated with recurrence risk) (vaz2022uncommonglioneuronaltumors pages 9-10)
WHO grade (grade 1 vs. grade 3)
CDKN2A/B deletion status

12. Treatment

Surgical Management (MAXO:0000004 - surgical procedure)

Gross total resection is the cornerstone of treatment and is considered curative for most WHO grade 1 glioneuronal tumors (crainic2023rareneuronalglial pages 1-2, crainic2023rareneuronalglial pages 6-8). For epilepsy-associated tumors, extended resection including the epileptogenic zone improves seizure-free outcomes (crainic2023rareneuronalglial pages 6-8). Temporal lobe surgeries generally achieve better seizure control than extratemporal resections.

Targeted Therapies (MAXO:0001525 - targeted therapy)

The following table summarizes the molecular targets and therapeutic options:

Target/Gene	Alteration Type	Frequency in tumor subtype	Associated tumor subtype(s)	Targeted therapy options	ESCAT classification / guideline status	Clinical trial evidence (NCT)
BRAF	p.V600E missense hotspot	Ganglioglioma ~36.3–36.9%; DNET <1/3 of cases; PLNTY subset; broader mixed neuronal-glial tumor association in OpenTargets (pereira2026molecularfeaturesin pages 1-2, pereira2026molecularfeaturesin pages 2-4, crainic2023rareneuronalglial pages 6-8, bale2022the2021who pages 8-9, OpenTargets Search: mixed neuronal-glial tumor,ganglioglioma,glioneuronal tumor)	Ganglioglioma, anaplastic ganglioglioma, DNET, PLNTY, other LEAT/glioneuronal tumors	Dabrafenib + trametinib; vemurafenib; other BRAF inhibitors; BRAF/MEK combination preferred for progressive/recurrent disease after standard care (crainic2023rareneuronalglial pages 18-19, pereira2026molecularfeaturesin pages 4-5, capper2023eanoguidelineon pages 2-3, capper2023eanoguidelineon pages 9-10)	Standard-of-care target in recurrent CNS tumors/glioneuronal tumors per EANO; highest actionability among reviewed targets (capper2023eanoguidelineon pages 2-3, bent2025updatedeanoguideline pages 1-2, capper2023eanoguidelineon pages 9-10)	NCT02684058 (dabrafenib + trametinib, pediatric BRAF V600 tumors); pediatric long-term follow-up NCT03975829
BRAF	KIAA1549::BRAF fusion / other BRAF fusions	Common in some low-grade glioma/glioneuronal contexts; reported in DLGNT and pilocytic-spectrum tumors; not a dominant alteration in classic ganglioglioma (engelhardt2022frequentfgfr1hotspot pages 1-2, vaz2022uncommonglioneuronaltumors pages 6-7, bent2025updatedeanoguideline pages 3-4)	Diffuse leptomeningeal glioneuronal tumor (DLGNT), pilocytic-spectrum tumors, some mixed neuronal-glial tumors	MEK inhibitors or type II RAF inhibitors considered, preferably in trials for recurrent disease (capper2023eanoguidelineon pages 9-10)	Therapeutically relevant in selected entities including DLGNT; EANO update notes growing relevance of fusion testing (bent2025updatedeanoguideline pages 3-4)	No subtype-specific dedicated trial identified here; may be captured in basket/brain tumor molecular trials
FGFR1	Hotspot mutation (N546K, K656E), mutation/duplication/fusion spectrum	>75% in DNET overall FGFR1-altered spectrum; only ~1.18% in ganglioglioma; in driver-unknown LGG/MNGT, FGFR1 N546/K656 mutations in 12% (13/108) (crainic2023rareneuronalglial pages 6-8, engelhardt2022frequentfgfr1hotspot pages 1-2, pereira2026molecularfeaturesin pages 1-2)	DNET, RGNT, some mixed neuronal-glial tumors, pilocytic-spectrum tumors	FGFR inhibitors (investigational; modest activity so far); molecular testing recommended when targeted options sought (capper2023eanoguidelineon pages 2-3, capper2023eanoguidelineon pages 11-12)	ESCAT IIB for FGFR alterations in glioneuronal tumors such as RGNT/DNET per EANO (capper2023eanoguidelineon pages 11-12)	NCT05267106 (pemigatinib in FGFR1-3 altered primary CNS tumors; terminated)
NTRK1/2/3	Gene fusions	Rare; OpenTargets supports NTRK3 association with mixed neuronal-glial tumor/ganglioglioma (OpenTargets Search: mixed neuronal-glial tumor,ganglioglioma,glioneuronal tumor)	Rare glioneuronal tumors, mixed neuronal-glial tumors, ganglioglioma subset	Larotrectinib, entrectinib for fusion-positive recurrent disease, ideally in trials/registries (capper2023eanoguidelineon pages 2-3, capper2023eanoguidelineon pages 6-7, capper2023eanoguidelineon pages 11-12)	ESCAT IIB; EANO recommends testing in patients who exhausted standard therapy and are fit for targeted treatment (capper2023eanoguidelineon pages 2-3, capper2023eanoguidelineon pages 3-4, capper2023eanoguidelineon pages 11-12)	No mixed neuronal-glial subtype-specific NCT identified here; typically basket trial enrollment
PRKCA	Fusion (especially SLC44A1::PRKCA)	Characteristic / recurrent driver rather than population-frequency estimate provided (crainic2023rareneuronalglial pages 4-5, crainic2023rareneuronalglial pages 5-6, vaz2022uncommonglioneuronaltumors pages 4-6)	Papillary glioneuronal tumor (PGNT)	No established approved matched therapy in current EANO guidance; primarily diagnostic biomarker	Not assigned as an actionable standard target in cited EANO therapeutic recommendations; clinical benefit not established (capper2023eanoguidelineon pages 2-3)	No specific trial identified here
PDGFRA	p.K385 mutation	Defining recurrent alteration for myxoid glioneuronal tumor (MGT) (capper2023eanoguidelineon pages 11-12, xie2023lowgradeepilepsyassociatedneuroepithelial pages 2-3, bale2022the2021who pages 8-9)	Myxoid glioneuronal tumor	Currently mainly diagnostic; no standard targeted therapy established in cited guidance	Used as a diagnostic marker in EANO/WHO-era classification rather than validated therapeutic target (capper2023eanoguidelineon pages 11-12, bale2022the2021who pages 8-9)	No specific trial identified here
H3-3A (H3F3A)	Histone H3 alterations (e.g., H3 K27M in rare cases)	Rare in ganglioglioma (~0.74% in one systematic review context); OpenTargets association present (pereira2026molecularfeaturesin pages 2-4, OpenTargets Search: mixed neuronal-glial tumor,ganglioglioma,glioneuronal tumor)	Rare ganglioglioma/anaplastic ganglioglioma and mixed neuronal-glial tumors	No established targeted therapy in current glioneuronal standard care; investigational approaches only	Not a proven predictive target for routine targeted treatment in current EANO update (bent2025updatedeanoguideline pages 1-2)	No specific trial identified here
PTEN	Loss / pathway alteration	OpenTargets association present but no direct evidence count in cited dataset; may contribute to BRAFi resistance biology (OpenTargets Search: mixed neuronal-glial tumor,ganglioglioma,glioneuronal tumor, pereira2026molecularfeaturesin pages 4-5)	Mixed neuronal-glial tumor, resistant BRAF-mutant glioneuronal tumors	No established matched therapy in this disease context; relevant to resistance and PI3K/AKT/mTOR biology	Not validated as routine actionable target in current EANO guidance for glioneuronal tumors (bent2025updatedeanoguideline pages 1-2)	No specific trial identified here
NF1 / KRAS / PTPN11 / other RAS-MAPK genes	Somatic mutation / CNV gain / pathway activation	Defined adverse-outcome subgroup in ganglioglioma; exact subgroup small (8 PTPN11-altered GG in one series) (kobow2021moleculardiagnosticsin pages 2-4, pereira2026molecularfeaturesin pages 8-9, engelhardt2022frequentfgfr1hotspot pages 1-2)	Ganglioglioma with atypical histology/adverse seizure outcome; RGNT may carry NF1 co-alterations	No established approved subtype-specific therapy; MAPK-pathway inhibitors considered biologically relevant/investigational (pereira2026molecularfeaturesin pages 8-9, crainic2023rareneuronalglial pages 6-8)	Not established as standard actionable targets; testing may be considered when trials/advanced molecular profiling are pursued (capper2023eanoguidelineon pages 2-3, capper2023eanoguidelineon pages 9-10)	NCT04923126 (mirdametinib in low-grade glioma; includes MAPK-pathway disease context)
PIK3CA / PIK3R1	Co-mutations / PI3K pathway activation	Reported as co-alterations in RGNT and some glioneuronal tumors; no robust prevalence estimate here (crainic2023rareneuronalglial pages 4-5, vaz2022uncommonglioneuronaltumors pages 6-7)	Rosette-forming glioneuronal tumor, some mixed neuronal-glial tumors	No established approved targeted therapy in this indication; pathway relevance mainly mechanistic	Not established as routine actionable target in current EANO recommendations for glioneuronal tumors (capper2023eanoguidelineon pages 2-3, bent2025updatedeanoguideline pages 1-2)	No specific trial identified here
ETV6	Fusion partner in NTRK3-related events / association in OpenTargets	Rare; OpenTargets association only in current evidence set (OpenTargets Search: mixed neuronal-glial tumor,ganglioglioma,glioneuronal tumor)	Rare mixed neuronal-glial tumors / ganglioglioma-related fusion-positive cases	If part of ETV6::NTRK3, therapy would follow NTRK inhibitor pathway (larotrectinib/entrectinib)	Follows NTRK fusion actionability rather than ETV6 alone (capper2023eanoguidelineon pages 2-3, capper2023eanoguidelineon pages 11-12)	Basket trial/registry approach; no specific subtype trial identified here
IDH1	Mutation	Rare / generally not characteristic; OpenTargets association exists but classic glioneuronal tumors are usually IDH-wildtype (OpenTargets Search: mixed neuronal-glial tumor,ganglioglioma,glioneuronal tumor, pereira2026molecularfeaturesin pages 2-4, crainic2023rareneuronalglial pages 6-8)	Rare atypical ganglioglioma or misclassified tumors	No established role in routine therapy for classic mixed neuronal-glial tumors	More relevant to differential diagnosis than to standard targeted treatment in this entity group (bent2025updatedeanoguideline pages 1-2)	No specific trial identified here
MUTYH	Association only in OpenTargets	No supporting evidence count in cited OpenTargets dataset (OpenTargets Search: mixed neuronal-glial tumor,ganglioglioma,glioneuronal tumor)	Mixed neuronal-glial tumor	None established	No therapeutic actionability established	None identified

Table: This table summarizes the main molecular alterations linked to mixed neuronal-glial tumors and maps them to current or emerging targeted treatment options. It emphasizes where evidence is strongest—especially for BRAF V600E—and where alterations are primarily diagnostic rather than therapeutically validated.

BRAF V600E-targeted therapy: The EANO guideline (2023) recommends that BRAF p.V600E targeted treatment should be considered part of the standard of care for patients with recurrent gliomas, pending regulatory approval (capper2023eanoguidelineon pages 2-3). FDA-approved BRAF inhibitors include vemurafenib (Zelboraf), dabrafenib (Tafinlar), and encorafenib (Braftovi) (pereira2026molecularfeaturesin pages 4-5). Combination BRAF/MEK inhibitor therapy (e.g., dabrafenib + trametinib) is preferred as it can overcome resistance to single-agent BRAF inhibitors and has been shown to produce durable responses (crainic2023rareneuronalglial pages 18-19, capper2023eanoguidelineon pages 9-10). In a multi-institutional study of BRAF-mutant pediatric high-grade gliomas (including anaplastic gangliogliomas) treated with upfront molecular targeted therapy, 3-year progression-free and overall survival were 65% and 82%, respectively, superior to historical controls (rosenberg2022upfrontmoleculartargeted pages 5-6).

NTRK inhibitors: Larotrectinib and entrectinib have received conditional tumor-agnostic approval for NTRK fusion-positive tumors (capper2023eanoguidelineon pages 6-7). However, evidence of clinical benefit specifically in adult CNS tumors remains limited, and treatment should preferably occur within clinical trials (capper2023eanoguidelineon pages 2-3, capper2023eanoguidelineon pages 11-12).

FGFR inhibitors: Clinical trials have evaluated FGFR inhibitors (e.g., pemigatinib, NCT05267106) for FGFR-altered CNS tumors, though activity has been modest (capper2023eanoguidelineon pages 2-3, capper2023eanoguidelineon pages 11-12). FGFR alterations are classified as ESCAT IIB in glioneuronal tumors (capper2023eanoguidelineon pages 11-12).

Radiotherapy (MAXO:0000015 - radiation therapy)

Radiotherapy is reserved for subtotal resection of aggressive tumors, tumors in eloquent brain areas, or recurrent disease (crainic2023rareneuronalglial pages 6-8, talloa2022brafandmek pages 10-11). Focal radiation therapy should be used cautiously in young children due to long-term cognitive side effects (talloa2022brafandmek pages 10-11).

Chemotherapy

Temozolomide has limited evidence for improving survival but may be considered for anaplastic features or inoperable recurrent tumors (crainic2023rareneuronalglial pages 6-8). For DLGNT, bevacizumab has been used successfully in some cases (crainic2023rareneuronalglial pages 18-19).

Clinical Trials

NCT02684058: Dabrafenib + trametinib in pediatric BRAF V600 mutation-positive LGG/relapsed HGG (Phase 2, completed, 151 participants)
NCT04923126: Mirdametinib (MEK inhibitor) in children/adolescents/young adults with low-grade glioma (Phase 1/2, recruiting, 132 participants)
NCT05267106: Pemigatinib (FGFR inhibitor) in FGFR1-3 altered primary CNS tumors (Phase 2, terminated, 83 participants)
NCT05259605: EORTC observational study assessing treatment and outcome using WHO 2021 classification (recruiting, 1650 participants)

13. Prevention

Primary Prevention

No established primary prevention strategies exist for mixed neuronal-glial tumors. As these tumors arise from somatic mutations during neural development, there are no modifiable risk factors or vaccination strategies available.

Secondary Prevention (Early Detection)

Early neuroimaging (MRI) evaluation in children presenting with new-onset seizures
Genetic counseling for families with NF1 or other cancer predisposition syndromes
Epilepsy monitoring and evaluation for surgical candidacy in drug-resistant cases

Tertiary Prevention

Post-surgical surveillance imaging to monitor for recurrence
Long-term epilepsy follow-up and anti-seizure medication management
Neurocognitive monitoring and rehabilitation, particularly in pediatric patients

14. Other Species / Natural Disease

Limited data exist on naturally occurring mixed neuronal-glial tumors in other species. Ganglioglioma-like tumors have been rarely reported in veterinary neuropathology in domestic animals. BRAF V600E-equivalent mutations and MAPK pathway alterations have been identified in canine tumors, supporting evolutionary conservation of oncogenic mechanisms. However, no systematic comparative pathology data specific to glioneuronal tumors are available in the current literature.

15. Model Organisms

Genetic Models

Experimental models have demonstrated that expression of BRAF V600E in neural progenitors during embryonic development reproduces ganglioglioma histopathological features and leads to epileptic seizures (kobow2021moleculardiagnosticsin pages 2-4). These models have been crucial for understanding the developmental origin of these tumors and the mechanism of epileptogenicity.

Mouse models: Conditional BRAF V600E expression in neural progenitors (genetically engineered mouse models)
Cell lines: Patient-derived primary tumor cultures have been used for drug sensitivity studies

Model Limitations

Difficulty recapitulating the mixed neuronal-glial phenotype in full
Limited availability of immortalized cell lines due to the low-grade, slow-growing nature of most subtypes
Differences between murine and human neural development may affect translational relevance

Summary

Mixed neuronal-glial tumors are a diverse group of rare, predominantly low-grade CNS neoplasms characterized by dual neuronal-glial composition, strong association with epilepsy, and frequent MAPK pathway alterations. The WHO 2021 classification substantially expanded and refined this tumor family through integration of molecular markers and DNA methylation profiling. BRAF V600E is the most actionable therapeutic target, with dabrafenib/trametinib combination therapy approaching standard-of-care status for recurrent disease per EANO guidelines. Gross total surgical resection remains the primary curative modality, with excellent long-term survival exceeding 80% for WHO grade 1 subtypes. Ongoing molecular characterization continues to identify new tumor entities and refine prognostic stratification within this heterogeneous tumor group.

References

(crainic2023rareneuronalglial pages 1-2): Nicolas Crainic, Julia Furtner, Johan Pallud, Franck Bielle, Giuseppe Lombardi, Roberta Rudà, and Ahmed Idbaih. Rare neuronal, glial and glioneuronal tumours in adults. Cancers, 15:1120, Feb 2023. URL: https://doi.org/10.3390/cancers15041120, doi:10.3390/cancers15041120. This article has 7 citations.
(vaz2022uncommonglioneuronaltumors pages 1-4): A. Vaz, M.S. Cavalcanti, E.B. da Silva Junior, R. Ramina, and B.C. de Almeida Teixeira. Uncommon glioneuronal tumors: a radiologic and pathologic synopsis. American Journal of Neuroradiology, 43:1080-1089, May 2022. URL: https://doi.org/10.3174/ajnr.a7465, doi:10.3174/ajnr.a7465. This article has 25 citations and is from a peer-reviewed journal.
(bale2022the2021who pages 1-2): Tejus A. Bale and Marc K. Rosenblum. The 2021 who classification of tumors of the central nervous system: an update on pediatric low‐grade gliomas and glioneuronal tumors. Brain Pathology, Feb 2022. URL: https://doi.org/10.1111/bpa.13060, doi:10.1111/bpa.13060. This article has 279 citations and is from a domain leading peer-reviewed journal.
(bale2022the2021who pages 2-3): Tejus A. Bale and Marc K. Rosenblum. The 2021 who classification of tumors of the central nervous system: an update on pediatric low‐grade gliomas and glioneuronal tumors. Brain Pathology, Feb 2022. URL: https://doi.org/10.1111/bpa.13060, doi:10.1111/bpa.13060. This article has 279 citations and is from a domain leading peer-reviewed journal.
(OpenTargets Search: mixed neuronal-glial tumor,ganglioglioma,glioneuronal tumor): Open Targets Query (mixed neuronal-glial tumor,ganglioglioma,glioneuronal tumor, 20 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(pereira2026molecularfeaturesin pages 1-2): Benedito Jamilson Araújo Pereira, Sueli Mieko Oba-Shinjo, Ivy Karoline Herculano de Azevedo, Yuri Reis Casal, Wen Hung Tzu, Antônio Nogueira de Almeida, Wellingson Silva Paiva, and Suely Kazue Nagahashi Marie. Molecular features in gangliogliomas: a systematic review. Child's Nervous System, Feb 2026. URL: https://doi.org/10.1007/s00381-026-07170-7, doi:10.1007/s00381-026-07170-7. This article has 1 citations.
(pereira2026molecularfeaturesin pages 2-4): Benedito Jamilson Araújo Pereira, Sueli Mieko Oba-Shinjo, Ivy Karoline Herculano de Azevedo, Yuri Reis Casal, Wen Hung Tzu, Antônio Nogueira de Almeida, Wellingson Silva Paiva, and Suely Kazue Nagahashi Marie. Molecular features in gangliogliomas: a systematic review. Child's Nervous System, Feb 2026. URL: https://doi.org/10.1007/s00381-026-07170-7, doi:10.1007/s00381-026-07170-7. This article has 1 citations.
(crainic2023rareneuronalglial pages 6-8): Nicolas Crainic, Julia Furtner, Johan Pallud, Franck Bielle, Giuseppe Lombardi, Roberta Rudà, and Ahmed Idbaih. Rare neuronal, glial and glioneuronal tumours in adults. Cancers, 15:1120, Feb 2023. URL: https://doi.org/10.3390/cancers15041120, doi:10.3390/cancers15041120. This article has 7 citations.
(kobow2021moleculardiagnosticsin pages 2-4): Katja Kobow, Stéphanie Baulac, Andreas von Deimling, and Jeong Ho Lee. Molecular diagnostics in drug‐resistant focal epilepsy define new disease entities. Brain Pathology, Jul 2021. URL: https://doi.org/10.1111/bpa.12963, doi:10.1111/bpa.12963. This article has 25 citations and is from a domain leading peer-reviewed journal.
(xie2023lowgradeepilepsyassociatedneuroepithelial pages 2-3): Mingguo Xie, Xiongfei Wang, Zejun Duan, and Guoming Luan. Low-grade epilepsy-associated neuroepithelial tumors: tumor spectrum and diagnosis based on genetic alterations. Frontiers in Neuroscience, Jan 2023. URL: https://doi.org/10.3389/fnins.2022.1071314, doi:10.3389/fnins.2022.1071314. This article has 30 citations and is from a peer-reviewed journal.
(crainic2023rareneuronalglial pages 4-5): Nicolas Crainic, Julia Furtner, Johan Pallud, Franck Bielle, Giuseppe Lombardi, Roberta Rudà, and Ahmed Idbaih. Rare neuronal, glial and glioneuronal tumours in adults. Cancers, 15:1120, Feb 2023. URL: https://doi.org/10.3390/cancers15041120, doi:10.3390/cancers15041120. This article has 7 citations.
(vaz2022uncommonglioneuronaltumors pages 4-6): A. Vaz, M.S. Cavalcanti, E.B. da Silva Junior, R. Ramina, and B.C. de Almeida Teixeira. Uncommon glioneuronal tumors: a radiologic and pathologic synopsis. American Journal of Neuroradiology, 43:1080-1089, May 2022. URL: https://doi.org/10.3174/ajnr.a7465, doi:10.3174/ajnr.a7465. This article has 25 citations and is from a peer-reviewed journal.
(vaz2022uncommonglioneuronaltumors pages 6-7): A. Vaz, M.S. Cavalcanti, E.B. da Silva Junior, R. Ramina, and B.C. de Almeida Teixeira. Uncommon glioneuronal tumors: a radiologic and pathologic synopsis. American Journal of Neuroradiology, 43:1080-1089, May 2022. URL: https://doi.org/10.3174/ajnr.a7465, doi:10.3174/ajnr.a7465. This article has 25 citations and is from a peer-reviewed journal.
(singh2023currentstatusof pages 3-4): Jyotsna Singh, Saumya Sahu, Trishala Mohan, Swati Mahajan, Mehar C Sharma, Chitra Sarkar, and Vaishali Suri. Current status of dna methylation profiling in neuro-oncology as a diagnostic support tool: a review. Neuro-oncology practice, 10 6:518-526, Jul 2023. URL: https://doi.org/10.1093/nop/npad040, doi:10.1093/nop/npad040. This article has 11 citations and is from a peer-reviewed journal.
(bent2025updatedeanoguideline pages 3-4): Martin J van den Bent, Enrico Franceschi, Mehdi Touat, Pim J French, Ahmed Idbaih, Giuseppe Lombardi, Roberta Rudà, Leonille Schweizer, David Capper, Marc Sanson, Pieter Wesseling, Michael Weller, Marica Eoli, Elena Anghileri, Franck Bielle, Phillipp Euskirchen, Marjolein Geurts, Patrick Y Wen, and Matthias Preusser. Updated eano guideline on rational molecular testing of gliomas, glioneuronal, and neuronal tumors in adults for targeted therapy selection—update 1. Neuro-Oncology, 27:331-337, Oct 2025. URL: https://doi.org/10.1093/neuonc/noae213, doi:10.1093/neuonc/noae213. This article has 27 citations and is from a domain leading peer-reviewed journal.
(rio2024newcnstumor pages 2-4): Ramiro José del Río, Santiago Ezequiel Cicutti, Daniel C. Moreira, and Javier Danilo Gonzalez Ramos. New cns tumor classification: the importance in pediatric neurosurgical practice. Surgical Neurology International, 15:130, Apr 2024. URL: https://doi.org/10.25259/sni_681_2023, doi:10.25259/sni_681_2023. This article has 2 citations and is from a peer-reviewed journal.
(bale2022the2021who pages 8-9): Tejus A. Bale and Marc K. Rosenblum. The 2021 who classification of tumors of the central nervous system: an update on pediatric low‐grade gliomas and glioneuronal tumors. Brain Pathology, Feb 2022. URL: https://doi.org/10.1111/bpa.13060, doi:10.1111/bpa.13060. This article has 279 citations and is from a domain leading peer-reviewed journal.
(capper2023eanoguidelineon pages 11-12): David Capper, Guido Reifenberger, Pim J French, Leonille Schweizer, Michael Weller, Mehdi Touat, Simone P Niclou, Philipp Euskirchen, Christine Haberler, Monika E Hegi, Sebastian Brandner, Emilie Le Rhun, Roberta Rudà, Marc Sanson, Ghazaleh Tabatabai, Felix Sahm, Patrick Y Wen, Pieter Wesseling, Matthias Preusser, and Martin J van den Bent. Eano guideline on rational molecular testing of gliomas, glioneuronal, and neuronal tumors in adults for targeted therapy selection. Neuro-Oncology, 25:813-826, Jan 2023. URL: https://doi.org/10.1093/neuonc/noad008, doi:10.1093/neuonc/noad008. This article has 129 citations and is from a domain leading peer-reviewed journal.
(bale2022the2021who pages 5-6): Tejus A. Bale and Marc K. Rosenblum. The 2021 who classification of tumors of the central nervous system: an update on pediatric low‐grade gliomas and glioneuronal tumors. Brain Pathology, Feb 2022. URL: https://doi.org/10.1111/bpa.13060, doi:10.1111/bpa.13060. This article has 279 citations and is from a domain leading peer-reviewed journal.
(crainic2023rareneuronalglial pages 5-6): Nicolas Crainic, Julia Furtner, Johan Pallud, Franck Bielle, Giuseppe Lombardi, Roberta Rudà, and Ahmed Idbaih. Rare neuronal, glial and glioneuronal tumours in adults. Cancers, 15:1120, Feb 2023. URL: https://doi.org/10.3390/cancers15041120, doi:10.3390/cancers15041120. This article has 7 citations.
(bale2022the2021who pages 3-5): Tejus A. Bale and Marc K. Rosenblum. The 2021 who classification of tumors of the central nervous system: an update on pediatric low‐grade gliomas and glioneuronal tumors. Brain Pathology, Feb 2022. URL: https://doi.org/10.1111/bpa.13060, doi:10.1111/bpa.13060. This article has 279 citations and is from a domain leading peer-reviewed journal.
(vaz2022uncommonglioneuronaltumors pages 8-9): A. Vaz, M.S. Cavalcanti, E.B. da Silva Junior, R. Ramina, and B.C. de Almeida Teixeira. Uncommon glioneuronal tumors: a radiologic and pathologic synopsis. American Journal of Neuroradiology, 43:1080-1089, May 2022. URL: https://doi.org/10.3174/ajnr.a7465, doi:10.3174/ajnr.a7465. This article has 25 citations and is from a peer-reviewed journal.
(pereira2026molecularfeaturesin pages 4-5): Benedito Jamilson Araújo Pereira, Sueli Mieko Oba-Shinjo, Ivy Karoline Herculano de Azevedo, Yuri Reis Casal, Wen Hung Tzu, Antônio Nogueira de Almeida, Wellingson Silva Paiva, and Suely Kazue Nagahashi Marie. Molecular features in gangliogliomas: a systematic review. Child's Nervous System, Feb 2026. URL: https://doi.org/10.1007/s00381-026-07170-7, doi:10.1007/s00381-026-07170-7. This article has 1 citations.
(engelhardt2022frequentfgfr1hotspot pages 1-2): Sophie Engelhardt, Felix Behling, Rudi Beschorner, Franziska Eckert, Patricia Kohlhof, Marcos Tatagiba, Ghazaleh Tabatabai, Martin U. Schuhmann, Martin Ebinger, and Jens Schittenhelm. Frequent fgfr1 hotspot alterations in driver-unknown low-grade glioma and mixed neuronal-glial tumors. Journal of Cancer Research and Clinical Oncology, 148:857-866, Jan 2022. URL: https://doi.org/10.1007/s00432-021-03906-x, doi:10.1007/s00432-021-03906-x. This article has 25 citations and is from a peer-reviewed journal.
(pereira2026molecularfeaturesin pages 8-9): Benedito Jamilson Araújo Pereira, Sueli Mieko Oba-Shinjo, Ivy Karoline Herculano de Azevedo, Yuri Reis Casal, Wen Hung Tzu, Antônio Nogueira de Almeida, Wellingson Silva Paiva, and Suely Kazue Nagahashi Marie. Molecular features in gangliogliomas: a systematic review. Child's Nervous System, Feb 2026. URL: https://doi.org/10.1007/s00381-026-07170-7, doi:10.1007/s00381-026-07170-7. This article has 1 citations.
(ostrom2021cbtrusstatisticalreport pages 50-51): Quinn T Ostrom, Gino Cioffi, Kristin Waite, Carol Kruchko, and Jill S Barnholtz-Sloan. Cbtrus statistical report: primary brain and other central nervous system tumors diagnosed in the united states in 2014-2018. Neuro-oncology, 23 Supplement_3:iii1-iii105, Oct 2021. URL: https://doi.org/10.1093/neuonc/noab200, doi:10.1093/neuonc/noab200. This article has 1958 citations and is from a domain leading peer-reviewed journal.
(iijima2024genotyperelevantneuroimagingfeatures pages 9-9): Keiya Iijima, Hiroyuki Fujii, Fumio Suzuki, Kumiko Murayama, Yu-ichi Goto, Yuko Saito, Terunori Sano, Hiroyoshi Suzuki, Hajime Miyata, Yukio Kimura, Takuma Nakashima, Hiromichi Suzuki, Masaki Iwasaki, and Noriko Sato. Genotype-relevant neuroimaging features in low-grade epilepsy-associated tumors. Frontiers in Neurology, Jul 2024. URL: https://doi.org/10.3389/fneur.2024.1419104, doi:10.3389/fneur.2024.1419104. This article has 2 citations and is from a peer-reviewed journal.
(capper2023eanoguidelineon pages 3-4): David Capper, Guido Reifenberger, Pim J French, Leonille Schweizer, Michael Weller, Mehdi Touat, Simone P Niclou, Philipp Euskirchen, Christine Haberler, Monika E Hegi, Sebastian Brandner, Emilie Le Rhun, Roberta Rudà, Marc Sanson, Ghazaleh Tabatabai, Felix Sahm, Patrick Y Wen, Pieter Wesseling, Matthias Preusser, and Martin J van den Bent. Eano guideline on rational molecular testing of gliomas, glioneuronal, and neuronal tumors in adults for targeted therapy selection. Neuro-Oncology, 25:813-826, Jan 2023. URL: https://doi.org/10.1093/neuonc/noad008, doi:10.1093/neuonc/noad008. This article has 129 citations and is from a domain leading peer-reviewed journal.
(vaz2022uncommonglioneuronaltumors pages 9-10): A. Vaz, M.S. Cavalcanti, E.B. da Silva Junior, R. Ramina, and B.C. de Almeida Teixeira. Uncommon glioneuronal tumors: a radiologic and pathologic synopsis. American Journal of Neuroradiology, 43:1080-1089, May 2022. URL: https://doi.org/10.3174/ajnr.a7465, doi:10.3174/ajnr.a7465. This article has 25 citations and is from a peer-reviewed journal.
(crainic2023rareneuronalglial pages 18-19): Nicolas Crainic, Julia Furtner, Johan Pallud, Franck Bielle, Giuseppe Lombardi, Roberta Rudà, and Ahmed Idbaih. Rare neuronal, glial and glioneuronal tumours in adults. Cancers, 15:1120, Feb 2023. URL: https://doi.org/10.3390/cancers15041120, doi:10.3390/cancers15041120. This article has 7 citations.
(capper2023eanoguidelineon pages 2-3): David Capper, Guido Reifenberger, Pim J French, Leonille Schweizer, Michael Weller, Mehdi Touat, Simone P Niclou, Philipp Euskirchen, Christine Haberler, Monika E Hegi, Sebastian Brandner, Emilie Le Rhun, Roberta Rudà, Marc Sanson, Ghazaleh Tabatabai, Felix Sahm, Patrick Y Wen, Pieter Wesseling, Matthias Preusser, and Martin J van den Bent. Eano guideline on rational molecular testing of gliomas, glioneuronal, and neuronal tumors in adults for targeted therapy selection. Neuro-Oncology, 25:813-826, Jan 2023. URL: https://doi.org/10.1093/neuonc/noad008, doi:10.1093/neuonc/noad008. This article has 129 citations and is from a domain leading peer-reviewed journal.
(capper2023eanoguidelineon pages 9-10): David Capper, Guido Reifenberger, Pim J French, Leonille Schweizer, Michael Weller, Mehdi Touat, Simone P Niclou, Philipp Euskirchen, Christine Haberler, Monika E Hegi, Sebastian Brandner, Emilie Le Rhun, Roberta Rudà, Marc Sanson, Ghazaleh Tabatabai, Felix Sahm, Patrick Y Wen, Pieter Wesseling, Matthias Preusser, and Martin J van den Bent. Eano guideline on rational molecular testing of gliomas, glioneuronal, and neuronal tumors in adults for targeted therapy selection. Neuro-Oncology, 25:813-826, Jan 2023. URL: https://doi.org/10.1093/neuonc/noad008, doi:10.1093/neuonc/noad008. This article has 129 citations and is from a domain leading peer-reviewed journal.
(bent2025updatedeanoguideline pages 1-2): Martin J van den Bent, Enrico Franceschi, Mehdi Touat, Pim J French, Ahmed Idbaih, Giuseppe Lombardi, Roberta Rudà, Leonille Schweizer, David Capper, Marc Sanson, Pieter Wesseling, Michael Weller, Marica Eoli, Elena Anghileri, Franck Bielle, Phillipp Euskirchen, Marjolein Geurts, Patrick Y Wen, and Matthias Preusser. Updated eano guideline on rational molecular testing of gliomas, glioneuronal, and neuronal tumors in adults for targeted therapy selection—update 1. Neuro-Oncology, 27:331-337, Oct 2025. URL: https://doi.org/10.1093/neuonc/noae213, doi:10.1093/neuonc/noae213. This article has 27 citations and is from a domain leading peer-reviewed journal.
(capper2023eanoguidelineon pages 6-7): David Capper, Guido Reifenberger, Pim J French, Leonille Schweizer, Michael Weller, Mehdi Touat, Simone P Niclou, Philipp Euskirchen, Christine Haberler, Monika E Hegi, Sebastian Brandner, Emilie Le Rhun, Roberta Rudà, Marc Sanson, Ghazaleh Tabatabai, Felix Sahm, Patrick Y Wen, Pieter Wesseling, Matthias Preusser, and Martin J van den Bent. Eano guideline on rational molecular testing of gliomas, glioneuronal, and neuronal tumors in adults for targeted therapy selection. Neuro-Oncology, 25:813-826, Jan 2023. URL: https://doi.org/10.1093/neuonc/noad008, doi:10.1093/neuonc/noad008. This article has 129 citations and is from a domain leading peer-reviewed journal.
(rosenberg2022upfrontmoleculartargeted pages 5-6): Tom Rosenberg, Kee Kiat Yeo, Audrey Mauguen, Sanda Alexandrescu, Sanjay P Prabhu, Jessica W Tsai, Seth Malinowski, Mrinal Joshirao, Karishma Parikh, Sameer Farouk Sait, Marc K Rosenblum, Jamal K Benhamida, George Michaiel, Hung N Tran, Sonika Dahiya, Kara Kachurak, Gregory K Friedman, Julie I Krystal, Michael A Huang, Ashley S Margol, Karen D Wright, Dolly Aguilera, Tobey J MacDonald, Susan N Chi, and Matthias A Karajannis. Upfront molecular targeted therapy for the treatment of braf-mutant pediatric high-grade glioma. Neuro-oncology, 24:1964-1975, Apr 2022. URL: https://doi.org/10.1093/neuonc/noac096, doi:10.1093/neuonc/noac096. This article has 62 citations and is from a domain leading peer-reviewed journal.
(talloa2022brafandmek pages 10-11): Dario Talloa, Silvia Triarico, Pierpaolo Agresti, Stefano Mastrangelo, Giorgio Attinà, Alberto Romano, Palma Maurizi, and Antonio Ruggiero. Braf and mek targeted therapies in pediatric central nervous system tumors. Cancers, 14:4264, Aug 2022. URL: https://doi.org/10.3390/cancers14174264, doi:10.3390/cancers14174264. This article has 34 citations.

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Subtypes

Pathophysiology

Pathograph

Phenotypes

Genetic Associations

Medical Actions

Clinical Trials

Source YAML

References & Deep Research

References

Deep Research

1. Disease Information

Overview

Key Identifiers

Subtypes per WHO 2021 Classification

2. Etiology

Disease Causal Factors

Genetic Risk Factors

Environmental and Lifestyle Risk Factors

Gene-Environment Interactions

3. Phenotypes

Primary Phenotypes

4. Genetic/Molecular Information

Causal Genes and Pathogenic Variants

Epigenetic Information

Chromosomal Abnormalities

5. Environmental Information

6. Mechanism / Pathophysiology

Molecular Pathways

Cellular Processes

Causal Chain

7. Anatomical Structures Affected

Primary Organs

Tissue and Cell Level

8. Temporal Development

Onset

Progression

9. Inheritance and Population

Epidemiology

Population Demographics

10. Diagnostics

Clinical Tests

Differential Diagnosis

11. Outcome/Prognosis

Survival and Mortality

Prognostic Factors

12. Treatment

Surgical Management (MAXO:0000004 - surgical procedure)

Targeted Therapies (MAXO:0001525 - targeted therapy)

Radiotherapy (MAXO:0000015 - radiation therapy)

Chemotherapy

Clinical Trials

13. Prevention

Primary Prevention

Secondary Prevention (Early Detection)

Tertiary Prevention

14. Other Species / Natural Disease

15. Model Organisms

Genetic Models

Model Limitations

Summary

Artifacts