Diffuse astrocytoma is an infiltrative glial neoplasm of the central nervous system characterised by diffuse parenchymal invasion of astrocytic tumour cells, with a strong tendency toward malignant progression to higher-grade glioma. Under the WHO 2021/CNS5 classification, "diffuse astrocytoma" is no longer a single morphologic grade-2 entity; it is now an umbrella for molecularly defined diffuse gliomas of astrocytic lineage, including IDH-mutant astrocytoma (adult-type, grades 2-4), diffuse midline glioma H3 K27-altered (paediatric-type, grade 4), diffuse hemispheric glioma H3 G34-mutant, and diffuse paediatric-type high-grade glioma H3-wildtype and IDH-wildtype. The defining biological feature across subtypes is diffuse infiltration of brain parenchyma along white-matter tracts, contrasted with the circumscribed growth of pilocytic astrocytoma. Common driver mechanisms include IDH1/2 neomorphic mutations producing the oncometabolite D-2-hydroxyglutarate (2-HG) with downstream global hypermethylation (G-CIMP), cooperating loss of ATRX and TP53 (adult astrocytic lineage), histone H3 oncomutations (K27M, G34R/V) acting as dominant-negative epigenetic drivers in paediatric tumours, and MGMT promoter methylation as a predictor of temozolomide response. Chromosome 1p/19q codeletion status is used here only to distinguish astrocytic from oligodendroglial lineage; the codeleted oligodendroglial entity is curated separately.
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name: Diffuse Astrocytoma
creation_date: '2026-05-14T10:00:00Z'
updated_date: '2026-05-14T10:00:00Z'
description: >-
Diffuse astrocytoma is an infiltrative glial neoplasm of the central nervous
system characterised by diffuse parenchymal invasion of astrocytic tumour
cells, with a strong tendency toward malignant progression to higher-grade
glioma. Under the WHO 2021/CNS5 classification, "diffuse astrocytoma" is no
longer a single morphologic grade-2 entity; it is now an umbrella for
molecularly defined diffuse gliomas of astrocytic lineage, including
IDH-mutant astrocytoma (adult-type, grades 2-4), diffuse midline glioma H3
K27-altered (paediatric-type, grade 4), diffuse hemispheric glioma H3
G34-mutant, and diffuse paediatric-type high-grade glioma H3-wildtype and
IDH-wildtype. The defining biological feature across subtypes is diffuse
infiltration of brain parenchyma along white-matter tracts, contrasted with
the circumscribed growth of pilocytic astrocytoma. Common driver mechanisms
include IDH1/2 neomorphic mutations producing the oncometabolite
D-2-hydroxyglutarate (2-HG) with downstream global hypermethylation
(G-CIMP), cooperating loss of ATRX and TP53 (adult astrocytic lineage),
histone H3 oncomutations (K27M, G34R/V) acting as dominant-negative
epigenetic drivers in paediatric tumours, and MGMT promoter methylation as a
predictor of temozolomide response. Chromosome 1p/19q codeletion status is
used here only to distinguish astrocytic from oligodendroglial lineage; the
codeleted oligodendroglial entity is curated separately.
categories:
- Central Nervous System Neoplasm
- Adult Brain Tumor
- Pediatric Brain Tumor
- Molecularly Defined Tumor
parents:
- diffuse glioma
has_subtypes:
- name: IDH-mutant
display_name: Astrocytoma, IDH-mutant (adult-type, grade 2-4)
description: >-
Adult-type diffuse astrocytic glioma defined by IDH1 or IDH2 mutation and
absence of 1p/19q codeletion. WHO CNS5 graded 2-4 based on histology
(mitoses, microvascular proliferation, necrosis) and CDKN2A/B homozygous
deletion. Curated in detail under IDH_Mutant_Astrocytoma.yaml.
subtype_term:
preferred_term: astrocytoma, IDH-mutant, grade 2
term:
id: MONDO:0956994
label: astrocytoma, IDH-mutant, grade 2
evidence:
- reference: PMID:26061751
reference_title: "Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "three robust, nonoverlapping, prognostically significant subtypes of lower-grade glioma that were captured more accurately by IDH, 1p/19q, and TP53 status than by histologic class"
explanation: TCGA defines IDH-mutant astrocytic glioma (IDH-mutant, 1p/19q-intact, TP53-mutant) as one of three molecular subtypes that supersede histology, supporting the IDH-mutant subtype assignment.
- name: DMG H3K27-altered
display_name: Diffuse midline glioma, H3 K27-altered (paediatric-type, grade 4)
description: >-
Highly aggressive paediatric-predominant midline glioma defined by H3 K27M
mutation (H3F3A/HIST1H3B/C), EZHIP overexpression, or other mechanisms
causing global H3K27me3 loss. Universally WHO grade 4. Curated in detail
under H3_K27_Altered_Diffuse_Midline_Glioma.yaml.
subtype_term:
preferred_term: diffuse midline glioma, H3 K27-altered
term:
id: MONDO:1060171
label: diffuse midline glioma, H3 K27-altered
evidence:
- reference: PMID:35169084
reference_title: "[Diffuse midline glioma]."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Diffuse midline glioma(DMG), H3 K27M-mutant is an infiltrative midline high-grade glioma with predominantly astrocytic differentiation and a K27M mutation in either H3F3A or HIST1H3B/C."
explanation: Saito 2022 review supports the DMG H3 K27-altered subtype definition with astrocytic differentiation, midline location, and K27M mutation in H3F3A or HIST1H3B/C.
- name: DHG H3G34-mutant
display_name: Diffuse hemispheric glioma, H3 G34-mutant
description: >-
Hemispheric high-grade glioma of adolescents and young adults driven by
glycine-to-arginine or glycine-to-valine substitution at H3F3A position
G34. G34R/V mutations alter local chromatin and frequently co-occur with
ATRX and TP53 loss. WHO grade 4.
evidence:
- reference: PMID:23079654
reference_title: "Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "the two H3F3A mutations give rise to GBMs in separate anatomic compartments"
explanation: Sturm et al. show H3F3A K27M and G34 mutations occupy separate anatomic compartments (midline vs hemispheric), supporting DHG H3 G34-mutant as a distinct hemispheric subtype.
- name: Paediatric HGG
display_name: Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype
description: >-
Paediatric high-grade diffuse glioma lacking IDH and histone H3 driver
mutations. Heterogeneous molecular subgroups defined by methylation
profiling (RTK1, RTK2, MYCN). Aggressive course with poor prognosis.
evidence:
- reference: PMID:34185076
reference_title: "The 2021 WHO Classification of Tumors of the Central Nervous System: a summary."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "New tumor types and subtypes are introduced, some based on novel diagnostic technologies such as DNA methylome profiling."
explanation: WHO CNS5 introduces methylation-profiled subtypes including diffuse paediatric-type high-grade glioma H3-wildtype/IDH-wildtype, supporting recognition of this subtype.
pathophysiology:
- name: Diffuse Parenchymal Infiltration
description: >-
The defining biological behaviour of all diffuse astrocytomas is single-cell
infiltration of brain parenchyma along white-matter tracts and perineuronal
spaces, in contrast with the circumscribed growth of pilocytic and other
non-diffuse gliomas. This invasive pattern precludes complete surgical
resection and underlies recurrence at the resection margin or at distant
sites.
evidence:
- reference: PMID:34185076
reference_title: "The 2021 WHO Classification of Tumors of the Central Nervous System: a summary."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "the 2021 fifth edition introduces major changes that advance the role of molecular diagnostics in CNS tumor classification."
explanation: WHO CNS5 reframes diffuse astrocytoma as a molecularly defined umbrella entity rather than a single morphologic grade-2 lesion, supporting the diffuse-infiltration descriptor across subtypes.
cell_types:
- preferred_term: astrocyte
term:
id: CL:0000127
label: astrocyte
locations:
- preferred_term: brain
term:
id: UBERON:0000955
label: brain
- name: IDH1/2 Neomorphic Mutation and 2-HG Accumulation
description: >-
In the adult-type IDH-mutant subtype, heterozygous mutations in IDH1
(R132H most common) or IDH2 (R172) confer neomorphic activity, converting
alpha-ketoglutarate to the oncometabolite D-2-hydroxyglutarate (2-HG).
2-HG accumulates to millimolar concentrations and competitively inhibits
alpha-ketoglutarate-dependent dioxygenases.
evidence:
- reference: PMID:40916936
reference_title: "Isocitrate dehydrogenase mutation and microenvironment in gliomas: do immunotherapy approaches matter?"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "This unique immune microenvironment is shaped by 2-hydroxyglutarate (2-HG), an oncometabolite produced by mutant IDH."
explanation: Confirms 2-HG as the oncometabolite produced by mutant IDH in gliomas, supporting the neomorphic enzyme activity described in this mechanism.
cell_types:
- preferred_term: astrocyte
term:
id: CL:0000127
label: astrocyte
biological_processes:
- preferred_term: tricarboxylic acid cycle
modifier: ABNORMAL
term:
id: GO:0006099
label: tricarboxylic acid cycle
downstream:
- target: G-CIMP Hypermethylation and Blocked Differentiation
description: 2-HG inhibits TET and Jumonji demethylases, causing genome-wide hypermethylation
- name: G-CIMP Hypermethylation and Blocked Differentiation
description: >-
Inhibition of TET2 (DNA demethylase) and Jumonji-domain histone demethylases
by 2-HG produces the glioma CpG island methylator phenotype (G-CIMP) with
global DNA and histone hypermethylation. The resulting transcriptional
reprogramming blocks normal glial differentiation, sustaining cells in a
proliferative progenitor-like state.
evidence:
- reference: PMID:22343889
reference_title: "IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: "mutation of a single gene, isocitrate dehydrogenase 1 (IDH1), establishes G-CIMP by remodelling the methylome."
explanation: Turcan et al. demonstrate in primary human astrocytes that mutant IDH1 is sufficient to establish the glioma CpG island methylator phenotype, directly supporting the G-CIMP mechanism downstream of 2-HG.
biological_processes:
- preferred_term: DNA methylation
modifier: INCREASED
term:
id: GO:0006304
label: DNA modification
- preferred_term: glial cell differentiation
modifier: DECREASED
term:
id: GO:0010001
label: glial cell differentiation
downstream:
- target: ATRX/TP53 Cooperative Loss
description: G-CIMP background cooperates with ATRX/TP53 loss to define astrocytic lineage
- name: ATRX/TP53 Cooperative Loss
description: >-
In the adult IDH-mutant astrocytic lineage, ATRX loss-of-function mutations
co-occur with TP53 mutations at very high frequency (approximately 86% ATRX
and 94% TP53 in IDH-mutant non-codeleted lower-grade gliomas), and are
mutually exclusive with 1p/19q codeletion. ATRX loss licenses alternative
lengthening of telomeres (ALT); TP53 loss removes a key tumour-suppressor
checkpoint. The ATRX-mutant / TP53-mutant / 1p19q-intact triad operationally
defines astrocytic versus oligodendroglial differentiation in IDH-mutant
diffuse glioma.
evidence:
- reference: PMID:26061751
reference_title: "Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%)."
explanation: TCGA cohort directly quantifies the ATRX/TP53 cooperative loss in IDH-mutant non-codeleted (astrocytic-lineage) diffuse glioma.
cell_types:
- preferred_term: astrocyte
term:
id: CL:0000127
label: astrocyte
- name: H3 K27M Oncohistone Dominant-Negative PRC2 Inhibition
description: >-
In paediatric-type midline diffuse astrocytomas, the H3 K27M substitution
in H3F3A or HIST1H3B/C generates an oncohistone that, although present in
only a minority of total H3 molecules, sequesters and inhibits PRC2/EZH2.
Global loss of H3K27 trimethylation derepresses developmental and
proliferative programmes, driving aggressive growth in midline structures
(pons, thalamus, spinal cord).
evidence:
- reference: PMID:35169084
reference_title: "[Diffuse midline glioma]."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Diffuse midline glioma(DMG), H3 K27M-mutant is an infiltrative midline high-grade glioma with predominantly astrocytic differentiation and a K27M mutation in either H3F3A or HIST1H3B/C."
explanation: Saito 2022 confirms the H3 K27M oncohistone in H3F3A or HIST1H3B/C drives the midline paediatric-type subtype, supporting this mechanism's role in astrocytic-lineage diffuse midline glioma.
cell_types:
- preferred_term: astrocyte
term:
id: CL:0000127
label: astrocyte
molecular_functions:
- preferred_term: histone H3K27 methyltransferase activity
modifier: DECREASED
term:
id: GO:0046976
label: histone H3K27 methyltransferase activity
locations:
- preferred_term: pons
term:
id: UBERON:0000988
label: pons
- name: H3 G34R/V Hemispheric Oncohistone
description: >-
In diffuse hemispheric glioma of adolescents and young adults, H3F3A
glycine-to-arginine (G34R) or glycine-to-valine (G34V) substitutions alter
local chromatin near the H3 N-terminal tail, perturbing K36 methylation and
reprogramming gene expression in cis. G34-mutant tumours typically arise in
cerebral hemispheres and co-occur with ATRX loss, TP53 mutation, and
alternative lengthening of telomeres.
evidence:
- reference: PMID:22286061
reference_title: "Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Mutations in ATRX (α-thalassaemia/mental retardation syndrome X-linked) and DAXX (death-domain associated protein), encoding two subunits of a chromatin remodelling complex required for H3.3 incorporation at pericentric heterochromatin and telomeres, were identified in 31% of samples overall, and in 100% of tumours harbouring a G34R or G34V H3.3 mutation."
explanation: Schwartzentruber et al. demonstrate near-universal co-occurrence of ATRX mutation with H3.3 G34R/G34V hemispheric mutations, supporting the H3 G34 oncohistone mechanism with ATRX cooperation.
- reference: PMID:23079654
reference_title: "Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "the two H3F3A mutations give rise to GBMs in separate anatomic compartments"
explanation: Sturm et al. show that H3.3 K27M and G34 mutations define anatomically distinct subgroups (midline vs hemispheric), supporting separate hemispheric origin of G34-mutant tumours.
cell_types:
- preferred_term: astrocyte
term:
id: CL:0000127
label: astrocyte
- name: MGMT Promoter Methylation as a Therapy-Response Axis
description: >-
Methylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter
epigenetically silences MGMT expression and reduces tumour-cell capacity to
repair O6-methylguanine adducts generated by alkylating chemotherapy
(temozolomide). MGMT promoter methylation is a predictive biomarker for
temozolomide benefit and is enriched in IDH-mutant astrocytomas through the
G-CIMP background. It is a therapy-response axis, not an oncogenic driver
per se.
evidence:
- reference: PMID:15758010
reference_title: "MGMT gene silencing and benefit from temozolomide in glioblastoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylated MGMT promoter did not have such a benefit."
explanation: Hegi et al. establish in a randomized clinical trial that MGMT promoter methylation predicts temozolomide benefit, directly supporting MGMT as a therapy-response axis in diffuse astrocytic glioma.
biological_processes:
- preferred_term: DNA repair
modifier: DECREASED
term:
id: GO:0006281
label: DNA repair
- name: Chromosome 1p/19q Status Defines Astrocytic vs Oligodendroglial Lineage
description: >-
Whole-arm codeletion of chromosomes 1p and 19q, in the context of IDH
mutation, defines oligodendroglioma (curated separately). Its absence in
IDH-mutant diffuse glioma, together with ATRX loss and TP53 mutation,
operationally classifies the tumour as astrocytic. 1p/19q status is
therefore used here purely as a lineage discriminator, not as a driver of
astrocytic pathophysiology.
evidence:
- reference: PMID:36651583
reference_title: "IDH-mutant diffuse gliomas: tips and tricks in the era of genomic tumor classification."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "diffuse gliomas typically occurring in adults are classified as oligodendroglioma IDH-mutant and 1p/19q codeleted, astrocytoma IDH-mutant, and"
explanation: WHO CNS5 review confirms 1p/19q codeletion (in the context of IDH mutation) is the operational lineage discriminator separating oligodendroglioma from astrocytoma.
phenotypes:
- category: Neurological
name: Seizures
frequency: VERY_FREQUENT
description: >-
Seizures are the most common presenting symptom of supratentorial diffuse
astrocytoma, occurring in approximately 60-80% of patients. Lower-grade
tumours have higher seizure frequency than higher-grade lesions.
phenotype_term:
preferred_term: Seizure
term:
id: HP:0001250
label: Seizure
- category: Neurological
name: Headache
frequency: FREQUENT
description: >-
Headache from mass effect or raised intracranial pressure, particularly
in higher-grade tumours and those with peritumoural oedema.
phenotype_term:
preferred_term: Headache
term:
id: HP:0002315
label: Headache
- category: Neurological
name: Cognitive Impairment
frequency: FREQUENT
description: >-
Memory loss, executive dysfunction, and personality change, especially
with frontal lobe involvement.
phenotype_term:
preferred_term: Cognitive impairment
term:
id: HP:0100543
label: Cognitive impairment
- category: Neurological
name: Hemiparesis
frequency: FREQUENT
description: >-
Unilateral motor weakness is the most common focal neurological deficit
seen with diffuse astrocytomas affecting corticospinal pathways; other
focal deficits (sensory loss, aphasia, visual field defects) co-occur
depending on tumour location but are not enumerated separately here.
phenotype_term:
preferred_term: Hemiparesis
term:
id: HP:0001269
label: Hemiparesis
genetic:
- name: IDH1
association: Somatic Mutation
notes: >-
IDH1 R132H is the dominant driver in the adult-type IDH-mutant subtype
(>90% of IDH-mutant astrocytomas). Detectable by R132H-specific
immunohistochemistry; other R132 variants require sequencing.
- name: IDH2
association: Somatic Mutation
notes: >-
IDH2 R172 mutations account for ~3% of IDH-mutant diffuse gliomas and are
enriched in oligodendrogliomas; in astrocytic lineage they require
sequencing for detection.
- name: ATRX
association: Somatic Mutation
evidence:
- reference: PMID:26061751
reference_title: "Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%)."
explanation: TCGA cohort supports ATRX inactivation at 86% in IDH-mutant non-codeleted (astrocytic-lineage) lower-grade gliomas.
notes: >-
Inactivating ATRX mutations occur in ~70-86% of IDH-mutant astrocytomas
and are associated with alternative lengthening of telomeres (ALT). ATRX
loss is mutually exclusive with 1p/19q codeletion and is part of the
operational definition of astrocytic versus oligodendroglial lineage.
- name: TP53
association: Somatic Mutation
evidence:
- reference: PMID:26061751
reference_title: "Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%)."
explanation: TCGA cohort supports TP53 mutation at 94% in IDH-mutant non-codeleted (astrocytic-lineage) lower-grade gliomas.
notes: >-
TP53 mutations occur in up to 94% of IDH-mutant non-1p19q-codeleted
diffuse gliomas; in the WHO CNS5 framework they support an astrocytic
rather than oligodendroglial diagnosis.
- name: H3F3A
association: Somatic Mutation
evidence:
- reference: PMID:22286061
reference_title: "Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Recurrent mutations in H3F3A, which encodes the replication-independent histone 3 variant H3.3, were observed in 31% of tumours, and led to amino acid substitutions at two critical positions within the histone tail (K27M, G34R/G34V)"
explanation: Schwartzentruber et al. establish that H3F3A K27M and G34R/G34V mutations are recurrent drivers in paediatric high-grade glioma, supporting the H3F3A assignment for paediatric-type subtypes.
notes: >-
K27M mutations drive the midline paediatric-type subtype (DMG, H3
K27-altered). G34R or G34V substitutions drive the hemispheric
paediatric/young-adult subtype (DHG, H3 G34-mutant). H3F3A encodes the
replication-independent histone variant H3.3.
- name: HIST1H3B
association: Somatic Mutation
notes: >-
H3.1 K27M mutations in HIST1H3B (and less commonly HIST1H3C) drive a
subset of pontine paediatric midline diffuse astrocytomas (DIPG variant).
- name: CDKN2A
association: Homozygous Deletion
notes: >-
Homozygous deletion of CDKN2A/CDKN2B (9p21) upgrades IDH-mutant
astrocytoma to WHO grade 4 independent of histology and predicts poor
outcome.
- name: MGMT
association: Epigenetic Silencing
evidence:
- reference: PMID:15758010
reference_title: "MGMT gene silencing and benefit from temozolomide in glioblastoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Epigenetic silencing of the MGMT (O6-methylguanine-DNA methyltransferase) DNA-repair gene by promoter methylation compromises DNA repair and has been associated with longer survival in patients with glioblastoma who receive alkylating agents."
explanation: Hegi et al. directly establish MGMT promoter methylation as an epigenetic silencing event predictive of temozolomide benefit in diffuse astrocytic glioma.
notes: >-
Promoter methylation of MGMT silences expression and predicts response to
temozolomide; enriched in IDH-mutant tumours via the G-CIMP background.
- name: Chromosome 1p/19q
association: Co-deletion (Absence)
notes: >-
Whole-arm codeletion of 1p and 19q is required for the oligodendroglioma
diagnosis. Its absence, in the presence of IDH mutation and ATRX/TP53
alterations, defines astrocytic lineage in IDH-mutant diffuse glioma.
biochemical:
- name: 2-Hydroxyglutarate (2-HG)
notes: >-
D-2-hydroxyglutarate accumulates to millimolar intratumoural concentrations
in IDH-mutant astrocytomas. Detectable non-invasively by MR spectroscopy
(peak at 2.25 ppm). Serves as a pharmacodynamic biomarker for IDH-inhibitor
therapy.
histopathology:
- name: Diffuse Glioma
finding_term:
preferred_term: Diffuse Glioma
term:
id: NCIT:C129325
label: Diffuse Glioma
frequency: VERY_FREQUENT
description: >-
All molecularly defined subtypes of diffuse astrocytoma share the histologic
pattern of diffuse parenchymal infiltration by atypical astrocytic cells,
distinguishing them from circumscribed gliomas (e.g., pilocytic astrocytoma).
evidence:
- reference: PMID:36651583
reference_title: "IDH-mutant diffuse gliomas: tips and tricks in the era of genomic tumor classification."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "oligodendroglioma IDH-mutant and 1p/19q codeleted, astrocytoma IDH-mutant, and"
explanation: WHO CNS5 review lists astrocytoma IDH-mutant among diffuse gliomas, supporting the histopathologic class assignment.
treatments:
- name: Maximal Safe Resection
description: >-
Surgical resection maximising extent of resection while preserving
neurological function. Greater extent of resection is associated with
improved progression-free and overall survival across diffuse astrocytoma
subtypes; however, complete resection is rarely achievable because of the
infiltrative growth pattern.
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
- name: Radiation Therapy
description: >-
External beam radiation therapy is standard adjuvant treatment for higher
grade or high-risk diffuse astrocytomas. In paediatric DMG H3 K27-altered,
radiation provides only transient palliative benefit.
treatment_term:
preferred_term: radiation therapy
term:
id: MAXO:0000014
label: radiation therapy
- name: Temozolomide Chemotherapy
description: >-
Oral alkylating chemotherapy used adjuvantly and at recurrence. MGMT
promoter methylation predicts response and is enriched in IDH-mutant
astrocytomas via the G-CIMP background.
treatment_term:
preferred_term: chemotherapy
term:
id: MAXO:0000647
label: chemotherapy
- name: Vorasidenib (Mutant-IDH Inhibitor)
description: >-
Brain-penetrant dual mutant IDH1/IDH2 inhibitor approved for residual or
recurrent grade 2 IDH-mutant gliomas after the INDIGO trial demonstrated
significant progression-free survival improvement. Targets the IDH-mutant
subtype specifically.
treatment_term:
preferred_term: pharmacotherapy
term:
id: MAXO:0000058
label: pharmacotherapy
therapeutic_agent:
- preferred_term: vorasidenib
term:
id: NCIT:C152914
label: Vorasidenib
clinical_trials:
- name: NCT04164901
phase: PHASE_III
status: COMPLETED
description: >-
INDIGO — pivotal Phase 3, multicentre, randomised, double-blind,
placebo-controlled trial of vorasidenib (AG-881) in residual or recurrent
Grade 2 IDH-mutant glioma after surgery. Demonstrated significant
progression-free survival benefit and supported FDA approval of
vorasidenib for the IDH-mutant subtype.
target_phenotypes:
- preferred_term: Glioma
term:
id: HP:0009733
label: Glioma
evidence:
- reference: clinicaltrials:NCT04164901
supports: SUPPORT
snippet: "Study AG881-C-004 is a phase 3, multicenter, randomized, double-blind, placebo-controlled study comparing the efficacy of vorasidenib to placebo in participants with residual or recurrent Grade 2 glioma with an IDH1 or IDH2 mutation who have undergone surgery as their only treatment."
explanation: Trial summary confirms the INDIGO study design (Phase 3 vorasidenib vs placebo) and the IDH-mutant Grade 2 glioma target population.
disease_term:
preferred_term: diffuse astrocytoma
term:
id: MONDO:0016686
label: diffuse astrocytoma
classifications:
icdo_morphology:
classification_value: Glioma
harrisons_chapter:
- classification_value: cancer
- classification_value: solid tumor