🏷

Classifications

Harrison's Chapter

ICD-O Morphology

◆

Subtypes

3

IDH-Mutant Astrocytoma Grade 2

Low-grade diffuse astrocytoma with IDH mutation. Characterized by low cellularity, mild nuclear atypia, and absence of mitotic activity, microvascular proliferation, or necrosis. Patients typically present with seizures and have favorable prognosis with median survival of 10-15 years.

IDH-Mutant Astrocytoma Grade 3

Anaplastic astrocytoma with IDH mutation. Shows increased cellularity, nuclear atypia, and mitotic activity but lacks microvascular proliferation and necrosis. Median survival approximately 5-7 years.

IDH-Mutant Astrocytoma Grade 4

Astrocytoma with IDH mutation and either microvascular proliferation, necrosis, or homozygous CDKN2A/B deletion. Previously termed secondary glioblastoma. Despite grade 4 histology, prognosis is better than IDH-wildtype glioblastoma.

⚙

Pathophysiology

3

IDH1/2 Neomorphic Mutation

Heterozygous mutations in IDH1 (R132H most common, >90%) or IDH2 (R172) confer neomorphic enzyme activity, converting alpha-ketoglutarate to the oncometabolite D-2-hydroxyglutarate (2-HG). This occurs as an early clonal event in gliomagenesis.

astrocyte link

tricarboxylic acid cycle link ⚠ ABNORMAL

brain link

Downstream

2-HG Accumulation and Epigenetic Dysregulation Neomorphic IDH activity produces oncometabolite 2-HG

Show evidence (1 reference)

PMID:40916936 SUPPORT

"This unique immune microenvironment is shaped by 2-hydroxyglutarate (2-HG), an oncometabolite produced by mutant IDH."

This abstract directly states that mutant IDH produces 2-HG, supporting the neomorphic IDH activity described.

2-HG Accumulation and Epigenetic Dysregulation

D-2-hydroxyglutarate competitively inhibits alpha-ketoglutarate-dependent dioxygenases including TET2 (DNA demethylation) and Jumonji-domain histone demethylases. This results in global DNA hypermethylation (G-CIMP phenotype) and histone hypermethylation, blocking cellular differentiation.

DNA methylation link ↑ INCREASED cell differentiation link ↓ DECREASED

Downstream

Blocked Glial Differentiation Epigenetic changes prevent normal astrocyte differentiation

Blocked Glial Differentiation

Epigenetic dysregulation caused by 2-HG prevents normal glial differentiation programs, maintaining cells in a proliferative progenitor-like state. This contributes to tumor formation but also underlies the better prognosis compared to IDH-wildtype tumors due to retained differentiation potential.

astrocyte link

glial cell differentiation link ↓ DECREASED

✶

Histopathology

1

Diffuse Glioma VERY_FREQUENT

Diffuse gliomas include IDH-mutant astrocytoma and oligodendroglioma subtypes.

Show evidence (1 reference)

PMID:36651583 SUPPORT

"oligodendroglioma IDH-mutant and 1p/19q codeleted, astrocytoma IDH-mutant, and"

Abstract lists IDH-mutant oligodendroglioma and astrocytoma among diffuse gliomas.

⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

●

Phenotypes

4

Seizures VERY_FREQUENT Neurological HP:0001250

Headache FREQUENT Neurological HP:0002315

Cognitive Impairment FREQUENT Neurological HP:0100543

Focal Neurological Deficit FREQUENT Neurological HP:0007367

🧬

Genetic Associations

5

IDH1 (Somatic Mutation)

Show evidence (1 reference)

PMID:26061751 SUPPORT Human Clinical

"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"

TCGA data establishes IDH mutation status as a fundamental molecular classifier of lower-grade gliomas, more accurate than histologic class.

IDH2 (Somatic Mutation)

TP53 (Somatic Mutation)

Show evidence (1 reference)

PMID:26061751 SUPPORT Human Clinical

"Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%)."

TCGA data shows TP53 mutations in 94% of IDH-mutant non-codeleted (astrocytic) lower-grade gliomas.

ATRX (Somatic Mutation)

Show evidence (1 reference)

PMID:26061751 SUPPORT Human Clinical

"Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%)."

TCGA data shows ATRX inactivation in 86% of IDH-mutant non-codeleted (astrocytic) lower-grade gliomas.

CDKN2A (Homozygous Deletion)

💊

Treatments

4

Maximal Safe Resection

Action: surgical procedure MAXO:0000004

Surgical resection maximizing extent of resection while preserving neurological function is the initial treatment. Greater extent of resection correlates with improved outcomes.

Radiation Therapy

Action: radiation therapy MAXO:0000014

External beam radiation therapy is standard adjuvant treatment. Timing may be delayed in lower-grade tumors with favorable prognostic factors.

Temozolomide Chemotherapy

Action: chemotherapy MAXO:0000647

Alkylating chemotherapy with temozolomide is used adjuvantly and at recurrence. MGMT promoter methylation predicts response but is common in IDH-mutant tumors.

Vorasidenib (IDH1/2 Inhibitor)

Action: pharmacotherapy MAXO:0000058

Agent: vorasidenib ↗

Brain-penetrant dual IDH1/2 inhibitor approved for grade 2 IDH-mutant gliomas. INDIGO trial demonstrated significant improvement in progression-free survival. Represents first targeted therapy for this tumor type.

🔬

Biochemical Markers

1

2-Hydroxyglutarate (2-HG)

{ }

Source YAML

click to show

name: IDH-Mutant Astrocytoma
creation_date: '2026-01-26T02:55:13Z'
updated_date: '2026-04-11T21:17:25Z'
description: >-
  IDH-mutant astrocytoma is a diffuse glioma defined by mutations in isocitrate
  dehydrogenase 1 or 2 (IDH1/IDH2) and the absence of 1p/19q codeletion. Under the
  WHO 2021 classification, this molecularly defined entity encompasses tumors
  previously classified as diffuse astrocytoma (grade 2), anaplastic astrocytoma
  (grade 3), and astrocytic glioblastoma (grade 4). IDH mutations result in
  neomorphic enzyme activity producing D-2-hydroxyglutarate (2-HG), an oncometabolite
  that inhibits alpha-ketoglutarate-dependent dioxygenases, leading to global DNA
  hypermethylation (G-CIMP phenotype) and impaired cellular differentiation.
  Prognosis is significantly better than IDH-wildtype glioblastoma.
categories:
- Central Nervous System Neoplasm
- Adult Brain Tumor
- Molecularly Defined Tumor
parents:
- diffuse glioma
has_subtypes:
- name: IDH-Mutant Astrocytoma Grade 2
  description: >-
    Low-grade diffuse astrocytoma with IDH mutation. Characterized by low cellularity,
    mild nuclear atypia, and absence of mitotic activity, microvascular proliferation,
    or necrosis. Patients typically present with seizures and have favorable prognosis
    with median survival of 10-15 years.
- name: IDH-Mutant Astrocytoma Grade 3
  description: >-
    Anaplastic astrocytoma with IDH mutation. Shows increased cellularity, nuclear
    atypia, and mitotic activity but lacks microvascular proliferation and necrosis.
    Median survival approximately 5-7 years.
- name: IDH-Mutant Astrocytoma Grade 4
  description: >-
    Astrocytoma with IDH mutation and either microvascular proliferation, necrosis,
    or homozygous CDKN2A/B deletion. Previously termed secondary glioblastoma.
    Despite grade 4 histology, prognosis is better than IDH-wildtype glioblastoma.
pathophysiology:
- name: IDH1/2 Neomorphic Mutation
  description: >-
    Heterozygous mutations in IDH1 (R132H most common, >90%) or IDH2 (R172) confer
    neomorphic enzyme activity, converting alpha-ketoglutarate to the oncometabolite
    D-2-hydroxyglutarate (2-HG). This occurs as an early clonal event in gliomagenesis.
  evidence:
  - reference: PMID:40916936
    reference_title: "Isocitrate dehydrogenase mutation and microenvironment in gliomas: do immunotherapy approaches matter?"
    supports: SUPPORT
    snippet: "This unique immune microenvironment is shaped by 2-hydroxyglutarate (2-HG), an oncometabolite produced by mutant IDH."
    explanation: This abstract directly states that mutant IDH produces 2-HG, supporting the neomorphic IDH activity described.
  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
  locations:
  - preferred_term: brain
    term:
      id: UBERON:0000955
      label: brain
  downstream:
  - target: 2-HG Accumulation and Epigenetic Dysregulation
    description: Neomorphic IDH activity produces oncometabolite 2-HG
- name: 2-HG Accumulation and Epigenetic Dysregulation
  description: >-
    D-2-hydroxyglutarate competitively inhibits alpha-ketoglutarate-dependent
    dioxygenases including TET2 (DNA demethylation) and Jumonji-domain histone
    demethylases. This results in global DNA hypermethylation (G-CIMP phenotype)
    and histone hypermethylation, blocking cellular differentiation.
  biological_processes:
  - preferred_term: DNA methylation
    modifier: INCREASED
    term:
      id: GO:0006304
      label: DNA modification
  - preferred_term: cell differentiation
    modifier: DECREASED
    term:
      id: GO:0030154
      label: cell differentiation
  downstream:
  - target: Blocked Glial Differentiation
    description: Epigenetic changes prevent normal astrocyte differentiation
- name: Blocked Glial Differentiation
  description: >-
    Epigenetic dysregulation caused by 2-HG prevents normal glial differentiation
    programs, maintaining cells in a proliferative progenitor-like state. This
    contributes to tumor formation but also underlies the better prognosis
    compared to IDH-wildtype tumors due to retained differentiation potential.
  cell_types:
  - preferred_term: astrocyte
    term:
      id: CL:0000127
      label: astrocyte
  biological_processes:
  - preferred_term: glial cell differentiation
    modifier: DECREASED
    term:
      id: GO:0010001
      label: glial cell differentiation
histopathology:
- name: Diffuse Glioma
  finding_term:
    preferred_term: Diffuse Glioma
    term:
      id: NCIT:C129325
      label: Diffuse Glioma
  frequency: VERY_FREQUENT
  description: Diffuse gliomas include IDH-mutant astrocytoma and oligodendroglioma subtypes.
  evidence:
  - reference: PMID:36651583
    reference_title: "IDH-mutant diffuse gliomas: tips and tricks in the era of genomic tumor classification."
    supports: SUPPORT
    snippet: "oligodendroglioma IDH-mutant and 1p/19q codeleted, astrocytoma IDH-mutant, and"
    explanation: Abstract lists IDH-mutant oligodendroglioma and astrocytoma among diffuse gliomas.

phenotypes:
- category: Neurological
  name: Seizures
  frequency: VERY_FREQUENT
  description: >-
    Seizures are the most common presenting symptom, occurring in 60-80% of patients.
    Lower-grade tumors have higher seizure frequency. Seizures may be focal or
    generalized.
  phenotype_term:
    preferred_term: Seizure
    term:
      id: HP:0001250
      label: Seizure
- category: Neurological
  name: Headache
  frequency: FREQUENT
  description: >-
    Headache occurs due to mass effect and increased intracranial pressure.
  phenotype_term:
    preferred_term: Headache
    term:
      id: HP:0002315
      label: Headache
- category: Neurological
  name: Cognitive Impairment
  frequency: FREQUENT
  description: >-
    Cognitive dysfunction including memory problems and executive function deficits
    may occur depending on tumor location.
  phenotype_term:
    preferred_term: Cognitive impairment
    term:
      id: HP:0100543
      label: Cognitive impairment
- category: Neurological
  name: Focal Neurological Deficit
  frequency: FREQUENT
  description: >-
    Motor weakness, sensory changes, or language deficits depending on tumor
    location.
  phenotype_term:
    preferred_term: Focal neurological deficit
    term:
      id: HP:0007367
      label: Atrophy/Degeneration affecting the central nervous system
genetic:
- name: IDH1
  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: "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 data establishes IDH mutation status as a fundamental molecular classifier of lower-grade gliomas, more accurate than histologic class."
  notes: >-
    IDH1 R132H mutation accounts for >90% of IDH-mutant astrocytomas. Can be detected
    by R132H-specific immunohistochemistry. Other R132 variants (R132C, R132S, R132G)
    occur less frequently.
- name: IDH2
  association: Somatic Mutation
  notes: >-
    IDH2 R172 mutations occur in approximately 3% of IDH-mutant gliomas, more common
    in oligodendrogliomas. Requires sequencing for detection.
- 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 data shows TP53 mutations in 94% of IDH-mutant non-codeleted (astrocytic) lower-grade gliomas."
  notes: >-
    TP53 mutations are present in approximately 70% of IDH-mutant astrocytomas and
    are typically mutually exclusive with 1p/19q codeletion, helping distinguish
    astrocytomas from oligodendrogliomas.
- 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 data shows ATRX inactivation in 86% of IDH-mutant non-codeleted (astrocytic) lower-grade gliomas."
  notes: >-
    ATRX loss occurs in approximately 70% of IDH-mutant astrocytomas. Associated with
    alternative lengthening of telomeres (ALT). ATRX loss is mutually exclusive with
    1p/19q codeletion.
- name: CDKN2A
  association: Homozygous Deletion
  notes: >-
    Homozygous deletion of CDKN2A/CDKN2B (9p21) confers grade 4 status regardless
    of
    histological features and is associated with worse prognosis.
biochemical:
- name: 2-Hydroxyglutarate (2-HG)
  notes: >-
    D-2-hydroxyglutarate accumulates to millimolar concentrations in IDH-mutant tumors.
    Can be detected by MR spectroscopy (peak at 2.25 ppm) and serves as a non-invasive
    biomarker. Levels may decrease with effective therapy.
treatments:
- name: Maximal Safe Resection
  description: >-
    Surgical resection maximizing extent of resection while preserving neurological
    function is the initial treatment. Greater extent of resection correlates with
    improved outcomes.
  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. Timing may be
    delayed in lower-grade tumors with favorable prognostic factors.
  treatment_term:
    preferred_term: radiation therapy
    term:
      id: MAXO:0000014
      label: radiation therapy
- name: Temozolomide Chemotherapy
  description: >-
    Alkylating chemotherapy with temozolomide is used adjuvantly and at recurrence.
    MGMT promoter methylation predicts response but is common in IDH-mutant tumors.
  treatment_term:
    preferred_term: chemotherapy
    term:
      id: MAXO:0000647
      label: chemotherapy
- name: Vorasidenib (IDH1/2 Inhibitor)
  description: >-
    Brain-penetrant dual IDH1/2 inhibitor approved for grade 2 IDH-mutant gliomas.
    INDIGO trial demonstrated significant improvement in progression-free survival.
    Represents first targeted therapy for this tumor type.
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
    therapeutic_agent:
    - preferred_term: vorasidenib
      term:
        id: NCIT:C152914
        label: Vorasidenib
disease_term:
  preferred_term: astrocytoma, IDH-mutant, grade 2
  term:
    id: MONDO:0956994
    label: astrocytoma, IDH-mutant, grade 2

classifications:
  icdo_morphology:
    classification_value: Glioma
  harrisons_chapter:
  - classification_value: cancer
  - classification_value: solid tumor
references:
- reference: DOI:10.1007/s11060-023-04250-5
  title: Updates on the WHO diagnosis of IDH-mutant glioma
  found_in:
  - IDH_Mutant_Astrocytoma-deep-research-falcon.md
  findings:
  - statement: The WHO classification of Tumors of the Central Nervous System represents the international standard classification for brain tumors.
    supporting_text: The WHO classification of Tumors of the Central Nervous System represents the international standard classification for brain tumors.
    evidence:
    - reference: DOI:10.1007/s11060-023-04250-5
      reference_title: Updates on the WHO diagnosis of IDH-mutant glioma
      supports: SUPPORT
      evidence_source: OTHER
      snippet: The WHO classification of Tumors of the Central Nervous System represents the international standard classification for brain tumors.
      explanation: Deep research cited this publication as relevant literature for IDH Mutant Astrocytoma.
- reference: DOI:10.1007/s12094-024-03456-x
  title: SEOM-GEINO clinical guidelines for grade 2 gliomas (2023)
  found_in:
  - IDH_Mutant_Astrocytoma-deep-research-falcon.md
  findings:
  - statement: The 2021 World Health Organization (WHO) classification has updated the definition of grade 2 gliomas and the presence of isocitrate dehydrogenase (IDH) mutation has been deemed the cornerstone of diagnosis.
    supporting_text: The 2021 World Health Organization (WHO) classification has updated the definition of grade 2 gliomas and the presence of isocitrate dehydrogenase (IDH) mutation has been deemed the cornerstone of diagnosis.
    evidence:
    - reference: DOI:10.1007/s12094-024-03456-x
      reference_title: SEOM-GEINO clinical guidelines for grade 2 gliomas (2023)
      supports: SUPPORT
      evidence_source: OTHER
      snippet: The 2021 World Health Organization (WHO) classification has updated the definition of grade 2 gliomas and the presence of isocitrate dehydrogenase (IDH) mutation has been deemed the cornerstone of diagnosis.
      explanation: Deep research cited this publication as relevant literature for IDH Mutant Astrocytoma.
- reference: DOI:10.1038/s41582-022-00679-w
  title: Clinical implications of the 2021 edition of the WHO classification of central nervous system tumours
  found_in:
  - IDH_Mutant_Astrocytoma-deep-research-falcon.md
  findings:
  - statement: Clinical implications of the 2021 edition of the WHO classification of central nervous system tumours
    supporting_text: Clinical implications of the 2021 edition of the WHO classification of central nervous system tumours
- reference: DOI:10.1038/s41598-023-32153-y
  title: 'Genomic profiles of IDH-mutant gliomas: MYCN-amplified IDH-mutant astrocytoma had the worst prognosis'
  found_in:
  - IDH_Mutant_Astrocytoma-deep-research-falcon.md
  findings:
  - statement: 'Genomic profiles of IDH-mutant gliomas: MYCN-amplified IDH-mutant astrocytoma had the worst prognosis'
    supporting_text: This study aimed to find any ambiguous genetic outlier for “oligodendroglioma, IDH-mutant and 1p/19q-codeleted (O_IDH_mut)” and “astrocytoma, IDH-mutant (A_IDH_mut)” and to redefine the genetic landscape and prognostic factors of IDH-mutant gliomas.
    evidence:
    - reference: DOI:10.1038/s41598-023-32153-y
      reference_title: 'Genomic profiles of IDH-mutant gliomas: MYCN-amplified IDH-mutant astrocytoma had the worst prognosis'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: This study aimed to find any ambiguous genetic outlier for “oligodendroglioma, IDH-mutant and 1p/19q-codeleted (O_IDH_mut)” and “astrocytoma, IDH-mutant (A_IDH_mut)” and to redefine the genetic landscape and prognostic factors of IDH-mutant gliomas.
      explanation: Deep research cited this publication as relevant literature for IDH Mutant Astrocytoma.
- reference: DOI:10.1056/nejmoa2304194
  title: Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma
  found_in:
  - IDH_Mutant_Astrocytoma-deep-research-falcon.md
  findings:
  - statement: Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma
    supporting_text: Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma
- reference: DOI:10.1093/neuonc/noad158
  title: Epidemiology and survival of adult-type diffuse glioma in Belgium during the molecular era
  found_in:
  - IDH_Mutant_Astrocytoma-deep-research-falcon.md
  findings:
  - statement: Survival data of diffuse adult-type glioma is mostly based on prospective clinical trials or small retrospective cohort studies.
    supporting_text: Survival data of diffuse adult-type glioma is mostly based on prospective clinical trials or small retrospective cohort studies.
    evidence:
    - reference: DOI:10.1093/neuonc/noad158
      reference_title: Epidemiology and survival of adult-type diffuse glioma in Belgium during the molecular era
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Survival data of diffuse adult-type glioma is mostly based on prospective clinical trials or small retrospective cohort studies.
      explanation: Deep research cited this publication as relevant literature for IDH Mutant Astrocytoma.
- reference: DOI:10.1093/neuonc/noae009
  title: Prognostic value of DNA methylation subclassification, aneuploidy, and <i>CDKN2A/B</i> homozygous deletion in predicting clinical outcome of IDH mutant astrocytomas
  found_in:
  - IDH_Mutant_Astrocytoma-deep-research-falcon.md
  findings:
  - statement: Isocitrate dehydrogenase (IDH) mutant astrocytoma grading, until recently, has been entirely based on morphology.
    supporting_text: Isocitrate dehydrogenase (IDH) mutant astrocytoma grading, until recently, has been entirely based on morphology.
    evidence:
    - reference: DOI:10.1093/neuonc/noae009
      reference_title: Prognostic value of DNA methylation subclassification, aneuploidy, and <i>CDKN2A/B</i> homozygous deletion in predicting clinical outcome of IDH mutant astrocytomas
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Isocitrate dehydrogenase (IDH) mutant astrocytoma grading, until recently, has been entirely based on morphology.
      explanation: Deep research cited this publication as relevant literature for IDH Mutant Astrocytoma.
- reference: DOI:10.32074/1591-951x-823
  title: Adult type diffuse gliomas in the new 2021 WHO Classification
  found_in:
  - IDH_Mutant_Astrocytoma-deep-research-falcon.md
  findings:
  - statement: Adult type diffuse gliomas in the new 2021 WHO Classification
    supporting_text: Adult type diffuse gliomas in the new 2021 WHO Classification
- reference: DOI:10.3390/biomedicines12061349
  title: 'The 2021 World Health Organization Central Nervous System Tumor Classification: The Spectrum of Diffuse Gliomas'
  found_in:
  - IDH_Mutant_Astrocytoma-deep-research-falcon.md
  findings:
  - statement: The 2021 edition of the World Health Organization (WHO) classification of central nervous system tumors introduces significant revisions across various tumor types.
    supporting_text: The 2021 edition of the World Health Organization (WHO) classification of central nervous system tumors introduces significant revisions across various tumor types.
    evidence:
    - reference: DOI:10.3390/biomedicines12061349
      reference_title: 'The 2021 World Health Organization Central Nervous System Tumor Classification: The Spectrum of Diffuse Gliomas'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: The 2021 edition of the World Health Organization (WHO) classification of central nervous system tumors introduces significant revisions across various tumor types.
      explanation: Deep research cited this publication as relevant literature for IDH Mutant Astrocytoma.
- reference: DOI:10.3390/cancers16152752
  title: 'Targeting Isocitrate Dehydrogenase (IDH) in Solid Tumors: Current Evidence and Future Perspectives'
  found_in:
  - IDH_Mutant_Astrocytoma-deep-research-falcon.md
  findings:
  - statement: The isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) enzymes are involved in key metabolic processes in human cells, regulating differentiation, proliferation, and oxidative damage response.
    supporting_text: The isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) enzymes are involved in key metabolic processes in human cells, regulating differentiation, proliferation, and oxidative damage response.
    evidence:
    - reference: DOI:10.3390/cancers16152752
      reference_title: 'Targeting Isocitrate Dehydrogenase (IDH) in Solid Tumors: Current Evidence and Future Perspectives'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: The isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) enzymes are involved in key metabolic processes in human cells, regulating differentiation, proliferation, and oxidative damage response.
      explanation: Deep research cited this publication as relevant literature for IDH Mutant Astrocytoma.
- reference: DOI:10.3390/cimb45070335
  title: 'CDKN2A/B Homozygous Deletions in Astrocytomas: A Literature Review'
  found_in:
  - IDH_Mutant_Astrocytoma-deep-research-falcon.md
  findings:
  - statement: Genomic alterations of CDKN2A and CDKN2B in astrocytomas have been an evolving area of study for decades.
    supporting_text: Genomic alterations of CDKN2A and CDKN2B in astrocytomas have been an evolving area of study for decades.
    evidence:
    - reference: DOI:10.3390/cimb45070335
      reference_title: 'CDKN2A/B Homozygous Deletions in Astrocytomas: A Literature Review'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Genomic alterations of CDKN2A and CDKN2B in astrocytomas have been an evolving area of study for decades.
      explanation: Deep research cited this publication as relevant literature for IDH Mutant Astrocytoma.

📚

References & Deep Research

References

11

DOI:10.1007/s11060-023-04250-5

Updates on the WHO diagnosis of IDH-mutant glioma

1 finding

The WHO classification of Tumors of the Central Nervous System represents the international standard classification for brain tumors.

"The WHO classification of Tumors of the Central Nervous System represents the international standard classification for brain tumors."

Show evidence (1 reference)

DOI:10.1007/s11060-023-04250-5 SUPPORT Other

"The WHO classification of Tumors of the Central Nervous System represents the international standard classification for brain tumors."

Deep research cited this publication as relevant literature for IDH Mutant Astrocytoma.

DOI:10.1007/s12094-024-03456-x

SEOM-GEINO clinical guidelines for grade 2 gliomas (2023)

1 finding

The 2021 World Health Organization (WHO) classification has updated the definition of grade 2 gliomas and the presence of isocitrate dehydrogenase (IDH) mutation has been deemed the cornerstone of diagnosis.

"The 2021 World Health Organization (WHO) classification has updated the definition of grade 2 gliomas and the presence of isocitrate dehydrogenase (IDH) mutation has been deemed the cornerstone of diagnosis."

Show evidence (1 reference)

DOI:10.1007/s12094-024-03456-x SUPPORT Other

"The 2021 World Health Organization (WHO) classification has updated the definition of grade 2 gliomas and the presence of isocitrate dehydrogenase (IDH) mutation has been deemed the cornerstone of diagnosis."

Deep research cited this publication as relevant literature for IDH Mutant Astrocytoma.

DOI:10.1038/s41582-022-00679-w

Clinical implications of the 2021 edition of the WHO classification of central nervous system tumours

1 finding

Clinical implications of the 2021 edition of the WHO classification of central nervous system tumours

"Clinical implications of the 2021 edition of the WHO classification of central nervous system tumours"

DOI:10.1038/s41598-023-32153-y

Genomic profiles of IDH-mutant gliomas: MYCN-amplified IDH-mutant astrocytoma had the worst prognosis

1 finding

Genomic profiles of IDH-mutant gliomas: MYCN-amplified IDH-mutant astrocytoma had the worst prognosis

"This study aimed to find any ambiguous genetic outlier for “oligodendroglioma, IDH-mutant and 1p/19q-codeleted (O_IDH_mut)” and “astrocytoma, IDH-mutant (A_IDH_mut)” and to redefine the genetic landscape and prognostic factors of IDH-mutant gliomas."

Show evidence (1 reference)

DOI:10.1038/s41598-023-32153-y SUPPORT Human Clinical

"This study aimed to find any ambiguous genetic outlier for “oligodendroglioma, IDH-mutant and 1p/19q-codeleted (O_IDH_mut)” and “astrocytoma, IDH-mutant (A_IDH_mut)” and to redefine the genetic landscape and prognostic factors of IDH-mutant gliomas."

Deep research cited this publication as relevant literature for IDH Mutant Astrocytoma.

DOI:10.1056/nejmoa2304194

Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma

1 finding

Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma

"Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma"

DOI:10.1093/neuonc/noad158

Epidemiology and survival of adult-type diffuse glioma in Belgium during the molecular era

1 finding

Survival data of diffuse adult-type glioma is mostly based on prospective clinical trials or small retrospective cohort studies.

"Survival data of diffuse adult-type glioma is mostly based on prospective clinical trials or small retrospective cohort studies."

Show evidence (1 reference)

DOI:10.1093/neuonc/noad158 SUPPORT Human Clinical

"Survival data of diffuse adult-type glioma is mostly based on prospective clinical trials or small retrospective cohort studies."

Deep research cited this publication as relevant literature for IDH Mutant Astrocytoma.

DOI:10.1093/neuonc/noae009

Prognostic value of DNA methylation subclassification, aneuploidy, and <i>CDKN2A/B</i> homozygous deletion in predicting clinical outcome of IDH mutant astrocytomas

1 finding

Isocitrate dehydrogenase (IDH) mutant astrocytoma grading, until recently, has been entirely based on morphology.

"Isocitrate dehydrogenase (IDH) mutant astrocytoma grading, until recently, has been entirely based on morphology."

Show evidence (1 reference)

DOI:10.1093/neuonc/noae009 SUPPORT Human Clinical

"Isocitrate dehydrogenase (IDH) mutant astrocytoma grading, until recently, has been entirely based on morphology."

Deep research cited this publication as relevant literature for IDH Mutant Astrocytoma.

DOI:10.32074/1591-951x-823

Adult type diffuse gliomas in the new 2021 WHO Classification

1 finding

Adult type diffuse gliomas in the new 2021 WHO Classification

"Adult type diffuse gliomas in the new 2021 WHO Classification"

DOI:10.3390/biomedicines12061349

The 2021 World Health Organization Central Nervous System Tumor Classification: The Spectrum of Diffuse Gliomas

1 finding

The 2021 edition of the World Health Organization (WHO) classification of central nervous system tumors introduces significant revisions across various tumor types.

"The 2021 edition of the World Health Organization (WHO) classification of central nervous system tumors introduces significant revisions across various tumor types."

Show evidence (1 reference)

DOI:10.3390/biomedicines12061349 SUPPORT Human Clinical

"The 2021 edition of the World Health Organization (WHO) classification of central nervous system tumors introduces significant revisions across various tumor types."

Deep research cited this publication as relevant literature for IDH Mutant Astrocytoma.

DOI:10.3390/cancers16152752

Targeting Isocitrate Dehydrogenase (IDH) in Solid Tumors: Current Evidence and Future Perspectives

1 finding

The isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) enzymes are involved in key metabolic processes in human cells, regulating differentiation, proliferation, and oxidative damage response.

"The isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) enzymes are involved in key metabolic processes in human cells, regulating differentiation, proliferation, and oxidative damage response."

Show evidence (1 reference)

DOI:10.3390/cancers16152752 SUPPORT Human Clinical

"The isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) enzymes are involved in key metabolic processes in human cells, regulating differentiation, proliferation, and oxidative damage response."

Deep research cited this publication as relevant literature for IDH Mutant Astrocytoma.

DOI:10.3390/cimb45070335

CDKN2A/B Homozygous Deletions in Astrocytomas: A Literature Review

1 finding

Genomic alterations of CDKN2A and CDKN2B in astrocytomas have been an evolving area of study for decades.

"Genomic alterations of CDKN2A and CDKN2B in astrocytomas have been an evolving area of study for decades."

Show evidence (1 reference)

DOI:10.3390/cimb45070335 SUPPORT Human Clinical

"Genomic alterations of CDKN2A and CDKN2B in astrocytomas have been an evolving area of study for decades."

Deep research cited this publication as relevant literature for IDH Mutant Astrocytoma.

Deep Research

1

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Disease Characteristics Research Template

Edison Scientific Literature 38 citations 2026-04-05T17:22:17.344985

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Characteristics Research Template

Target Disease

Disease Name: IDH-Mutant Astrocytoma
MONDO ID: (if available)
Category:

Research Objectives

Please provide a comprehensive research report on IDH-Mutant Astrocytoma covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.

For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.

1. Disease Information

Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed

What is the disease? Provide a concise overview.
What are the key identifiers? (OMIM, Orphanet, ICD-10/ICD-11, MeSH, Mondo)
What are the common synonyms and alternative names?
Is the information derived from individual patients (e.g., EHR) or aggregated disease-level resources?

2. Etiology

Disease Causal Factors: What are the primary causes? (genetic, environmental, infectious, mechanistic)
Risk Factors:

Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases
Genetic risk factors (causal variants, susceptibility loci, modifier genes)
Environmental risk factors (toxins, lifestyle, occupational exposures, age, sex, family history)
Protective Factors:

Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases
Genetic protective factors (protective variants, modifier alleles)
Environmental protective factors (diet, lifestyle, exposures that reduce risk)
Gene-Environment Interactions: How do genetic and environmental factors interact to influence disease?

Search first: CTD, PubMed, PheGenI, GxE databases

3. Phenotypes

Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC

For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities

For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype

4. Genetic/Molecular Information

Causal Genes: Gene mutations or chromosomal abnormalities responsible for disease (gene symbols, OMIM IDs)

Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene
Pathogenic Variants:
Affected genes (gene symbols, HGNC IDs) > Search first: OMIM, NCBI Gene, Ensembl, HGNC, UniProt, GeneCards
Variant classification (pathogenic, likely pathogenic, VUS per ACMG/AMP guidelines) > Search first: ClinVar, ClinGen, ACMG/AMP guidelines, VarSome
Variant type/class (missense, frameshift, nonsense, splice-site, structural)
Allele frequency in population databases > Search first: gnomAD, 1000 Genomes, ExAC, TOPMed, dbSNP
Somatic vs germline origin > Search first: COSMIC (somatic), ClinVar, ICGC, TCGA
Functional consequences (loss of function, gain of function, dominant negative)
Modifier Genes: Genes that modify disease severity or expression
Epigenetic Information: DNA methylation, histone modifications, chromatin changes affecting disease

Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
Chromosomal Abnormalities: Large-scale genetic changes (aneuploidy, translocations, inversions)

Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser

5. Environmental Information

Environmental Factors: Non-genetic contributing factors (toxins, radiation, pollution, occupational exposure)

Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases
Lifestyle Factors: Behavioral factors (smoking, diet, exercise, alcohol consumption)

Search first: CDC databases, WHO, PubMed, NHANES
Infectious Agents: If applicable, pathogens causing or triggering disease (bacteria, viruses, fungi, parasites)

Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON

6. Mechanism / Pathophysiology

Molecular Pathways: Specific signaling cascades or biochemical pathways involved (Wnt, MAPK, mTOR, PI3K-AKT, etc.)

Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc
Cellular Processes: Cell-level mechanisms (apoptosis, autophagy, cell cycle dysregulation, inflammation, etc.)

Search first: Gene Ontology (GO), Reactome, KEGG, PubMed
Protein Dysfunction: How protein structure or function is altered (misfolding, aggregation, loss of function, gain of function)

Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold
Metabolic Changes: Alterations in metabolic processes (energy metabolism, lipid metabolism, amino acid metabolism)

Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA
Immune System Involvement: Role of immune response (autoimmunity, immunodeficiency, chronic inflammation)

Search first: ImmPort, Immunome Database, IEDB, Gene Ontology
Tissue Damage Mechanisms: How tissues/ are injured (oxidative stress, ischemia, fibrosis, necrosis)

Search first: PubMed, Gene Ontology, Reactome
Biochemical Abnormalities: Specific molecular defects (enzyme deficiencies, receptor dysfunction, ion channel defects)

Search first: BRENDA, UniProt, KEGG, OMIM, PubMed
Epigenetic Changes: DNA methylation, histone modifications affecting gene expression in disease

Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
Molecular Profiling (if available):
Transcriptomics/gene expression changes > Search first: GEO (Gene Expression Omnibus), ArrayExpress, GTEx, Human Cell Atlas, SRA
Proteomics findings > Search first: PRIDE, ProteomeXchange, Human Protein Atlas, STRING, BioGRID
Metabolomics signatures > Search first: MetaboLights, Metabolomics Workbench, HMDB, METLIN
Lipidomics alterations > Search first: LIPID MAPS, SwissLipids, LipidHome, Metabolomics Workbench
Genomic structural features > Search first: UCSC Genome Browser, Ensembl, NCBI, dbVar, DGV
Advanced Technologies (if applicable):
Single-cell analysis findings (cell-type specific mechanisms, cellular heterogeneity) > Search first: Human Cell Atlas, Single Cell Portal, GEO, CELLxGENE
Spatial transcriptomics findings > Search first: GEO, Spatial Research, Vizgen, 10x Genomics data
Multi-omics integration results > Search first: TCGA, ICGC, cBioPortal, LinkedOmics, PubMed
Functional genomics screens (CRISPR, RNAi) > Search first: DepMap, GenomeRNAi, PubMed, BioGRID ORCS

For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types

7. Anatomical Structures Affected

Organ Level:
Primary organs directly affected
Secondary organ involvement (complications, secondary effects)
Body systems involved (cardiovascular, nervous, digestive, respiratory, endocrine, etc.)

Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT
Tissue and Cell Level:
Specific tissue types affected (epithelial, connective, muscle, nervous)
Specific cell populations targeted (with Cell Ontology terms)

Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB
Subcellular Level:
Cellular compartments involved (mitochondria, nucleus, ER, lysosomes) (with GO Cellular Component terms)

Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas
Localization:
Specific anatomical sites (with UBERON terms) > Search first: FMA, Uberon, NeuroNames (for brain), SNOMED CT
Lateralization (unilateral, bilateral, asymmetric) > Search first: HPO, clinical literature, imaging databases

8. Temporal Development

Onset:
Typical age of onset (congenital, pediatric, adult, geriatric)
Onset pattern (acute, subacute, chronic, insidious)

Search first: OMIM, Orphanet, HPO, PubMed
Progression:
Disease stages (early, intermediate, advanced, end-stage) > Search first: Cancer Staging Manual (AJCC), WHO classifications, PubMed
Progression rate (rapid, slow, variable)
Disease course pattern (episodic, relapsing-remitting, progressive, stable)
Disease duration (self-limited, chronic lifelong)

Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM
Patterns:
Remission patterns (spontaneous, treatment-induced) > Search first: Clinical trial databases, disease registries, PubMed
Critical periods (time windows of vulnerability or opportunity for intervention) > Search first: PubMed, developmental biology databases, clinical guidelines

9. Inheritance and Population

Epidemiology:
Prevalence (cases per 100,000 at given time)
Incidence (new cases per 100,000 per year)

Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries
For Genetic Etiology:
Inheritance pattern (AD, AR, X-linked, mitochondrial, multifactorial, polygenic) > Search first: OMIM, Orphanet, ClinVar, GTR (Genetic Testing Registry)
Penetrance (complete, incomplete, age-dependent) > Search first: ClinVar, OMIM, PubMed, ClinGen
Expressivity (variable, consistent) > Search first: OMIM, ClinVar, PubMed
Genetic anticipation (increasing severity in successive generations) > Search first: OMIM, PubMed (especially for repeat expansion disorders)
Germline mosaicism > Search first: ClinVar, OMIM, genetic counseling literature, PubMed
Founder effects (population-specific mutations) > Search first: gnomAD, population genetics databases, PubMed
Consanguinity role > Search first: OMIM, population studies, genetic counseling resources
Carrier frequency > Search first: gnomAD, carrier screening databases, GeneReviews, GTR
Population Demographics:
Affected populations (ethnic or demographic groups with higher prevalence) > Search first: gnomAD, 1000 Genomes, PAGE Study, PubMed, population registries
Geographic distribution (endemic areas, regional variation) > Search first: WHO, CDC, GBD, Orphanet, geographic epidemiology databases
Geographic distribution of specific variants
Sex ratio (male:female) > Search first: Disease registries, OMIM, PubMed, epidemiological databases
Age distribution of affected individuals > Search first: CDC, disease registries, SEER, Orphanet

10. Diagnostics

Clinical Tests:
Laboratory tests (blood, urine, tissue chemistry, specific enzyme assays) > Search first: LOINC, LabTests Online, PubMed
Biomarkers (proteins, metabolites, genetic markers, circulating biomarkers) > Search first: FDA Biomarker List, BEST (Biomarkers, EndpointS, and other Tools), PubMed
Imaging studies (X-ray, CT, MRI, PET, ultrasound) > Search first: RadLex, DICOM, Radiopaedia, imaging databases
Functional tests (pulmonary function, cardiac stress tests) > Search first: LOINC, clinical guidelines, PubMed
Electrophysiology (EEG, EMG, ECG, nerve conduction studies) > Search first: LOINC, clinical neurophysiology databases, PubMed
Biopsy findings (histopathology, immunohistochemistry) > Search first: SNOMED CT, College of American Pathologists resources, PubMed
Pathology findings (microscopic examination) > Search first: SNOMED CT, Digital Pathology databases, PubMed
Genetic Testing:

Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen
Overview of recommended genetic testing approach
Whole genome sequencing (WGS) utility > Search first: GTR, ClinVar, GEL (Genomics England), gnomAD
Whole exome sequencing (WES) utility > Search first: GTR, ClinVar, OMIM, GeneMatcher
Gene panels (which panels, which genes) > Search first: GTR, ClinVar, laboratory-specific databases
Single gene testing > Search first: GTR, ClinVar, OMIM, GeneReviews
Chromosomal microarray (CMA) > Search first: DECIPHER, ClinVar, dbVar, ECARUCA
Karyotyping > Search first: Chromosome Abnormality Database, ClinVar, cytogenetics resources
FISH > Search first: ClinVar, cytogenetics databases, PubMed
Mitochondrial DNA testing > Search first: MITOMAP, MSeqDR, ClinVar, GTR
Repeat expansion testing > Search first: GTR, ClinVar, repeat expansion databases, PubMed
Omics-Based Diagnostics (if applicable):
RNA sequencing / transcriptomics > Search first: GEO, ArrayExpress, GTEx, RNA-seq databases
Proteomics > Search first: PRIDE, ProteomeXchange, FDA Biomarker database
Metabolomics > Search first: MetaboLights, Metabolomics Workbench, HMDB
Epigenomics > Search first: GEO, ENCODE, Roadmap Epigenomics, MethBase
Liquid biopsy > Search first: COSMIC, ClinVar, liquid biopsy databases, PubMed
Clinical Criteria:
Standardized diagnostic criteria (DSM, ICD, society guidelines) > Search first: DSM-5, ICD-11, clinical society guidelines, UpToDate
Differential diagnosis (other conditions to rule out, with distinguishing features) > Search first: DynaMed, UpToDate, clinical decision support systems
Screening:
Screening methods for asymptomatic individuals (newborn screening, carrier screening, cascade screening) > Search first: ACMG recommendations, CDC newborn screening, GTR

11. Outcome/Prognosis

Survival and Mortality:
Survival rate (5-year, 10-year, overall) > Search first: SEER, cancer registries, disease-specific registries, PubMed
Life expectancy (with and without treatment if applicable) > Search first: Orphanet, disease registries, actuarial databases, PubMed
Mortality rate > Search first: CDC, WHO, GBD, national mortality databases
Disease-specific mortality (deaths directly attributable to disease) > Search first: Disease registries, CDC Wonder, GBD, PubMed
Morbidity and Function:
Morbidity (disease-related disability and health impacts) > Search first: GBD, WHO, disability databases, PubMed
Disability outcomes (long-term functional impairments) > Search first: ICF (International Classification of Functioning), disability registries
Quality of life measures (EQ-5D, SF-36, PROMIS, disease-specific tools) > Search first: EQ-5D database, SF-36, PROMIS, PubMed
Disease Course:
Complications (secondary problems: infections, organ failure, etc.) > Search first: ICD codes, disease registries, clinical databases, PubMed
Recovery potential (likelihood and extent of recovery, with vs without treatment) > Search first: Natural history studies, rehabilitation databases, PubMed
Prediction:
Prognostic factors (age, disease severity, biomarkers, treatment response) > Search first: Prognostic models databases, clinical calculators, PubMed
Prognostic biomarkers (molecular markers predicting disease course) > Search first: FDA Biomarker database, PubMed, cancer prognostic databases

12. Treatment

Pharmacotherapy:
Pharmacological treatments (drug names, drug classes, mechanisms of action) > Search first: DrugBank, RxNorm, ATC classification, DailyMed, FDA databases
Pharmacogenomics (how genetic variants affect drug metabolism, efficacy, toxicity) > Search first: PharmGKB, CPIC (Clinical Pharmacogenetics), FDA Table of PGx Biomarkers
Advanced Therapeutics:
Gene therapy (viral vectors, CRISPR, gene replacement, gene editing) > Search first: ClinicalTrials.gov, FDA gene therapy database, ASGCT resources
Cell therapy (stem cell transplant, CAR-T, cellular therapeutics) > Search first: ClinicalTrials.gov, FDA cell therapy database, FACT standards
RNA-based therapies (ASOs, siRNA, mRNA therapies) > Search first: ClinicalTrials.gov, FDA approvals, PubMed
Targeted therapies (treatments directed at specific molecular targets) > Search first: My Cancer Genome, OncoKB, ClinicalTrials.gov, FDA approvals
Immunotherapies (checkpoint inhibitors, monoclonal antibodies) > Search first: Cancer Immunotherapy Database, FDA approvals, ClinicalTrials.gov
Surgical and Interventional:
Surgical interventions (types of surgery, timing, outcomes) > Search first: CPT codes, surgical registries, clinical guidelines, PubMed
Supportive and Rehabilitative:
Supportive care (symptom management, pain control, nutrition) > Search first: Clinical guidelines, Cochrane Library, PubMed
Rehabilitation (physical therapy, occupational therapy, speech therapy) > Search first: Rehabilitation medicine databases, clinical guidelines, PubMed
Experimental:
Experimental treatments in clinical trials (with NCT identifiers if available) > Search first: ClinicalTrials.gov, EU Clinical Trials Register, WHO ICTRP
Treatment Outcomes:
Treatment response rates > Search first: Clinical trial databases, FDA reviews, systematic reviews, PubMed
Side effects and adverse events > Search first: FDA Adverse Event Reporting System (FAERS), MedWatch, PubMed
Treatment Strategy:
Treatment algorithms (clinical pathways, decision trees) > Search first: Clinical practice guidelines, NCCN Guidelines, UpToDate
Combination therapies > Search first: ClinicalTrials.gov, treatment guidelines, PubMed
Personalized medicine approaches (genotype-guided treatment) > Search first: My Cancer Genome, CIViC, PharmGKB, precision medicine databases

For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.

13. Prevention

Prevention Levels:
Primary prevention (preventing disease occurrence: vaccination, risk factor modification) > Search first: CDC, WHO, USPSTF recommendations, Cochrane Library
Secondary prevention (early detection and treatment: screening programs, early intervention) > Search first: USPSTF, CDC screening guidelines, WHO
Tertiary prevention (preventing complications in those with disease) > Search first: Clinical guidelines, disease management protocols, PubMed
Immunization: Vaccine strategies (if applicable)

Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database
Screening and Early Detection:
Screening programs (population-based: newborn screening, cancer screening) > Search first: CDC screening programs, USPSTF, cancer screening databases
Genetic screening (carrier screening, preimplantation genetic diagnosis, prenatal testing) > Search first: ACMG recommendations, ACOG guidelines, GTR
Risk stratification (identifying high-risk individuals for targeted prevention) > Search first: Risk prediction models, clinical calculators, PubMed
Behavioral Interventions: Lifestyle modifications to reduce risk

Search first: CDC, WHO, behavioral intervention databases, Cochrane Library
Counseling: Genetic counseling (risk assessment, family planning guidance)

Search first: NSGC resources, ACMG guidelines, GeneReviews
Public Health:
Public health interventions (sanitation, vector control, health education) > Search first: CDC, WHO, public health databases, PubMed
Environmental interventions (reducing environmental risk factors) > Search first: EPA databases, WHO environmental health, PubMed
Prophylaxis: Preventive medications or procedures

Search first: Clinical guidelines, FDA approvals, PubMed

14. Other Species / Natural Disease

Taxonomy: Species affected (with NCBI Taxon identifiers)

Search first: NCBI Taxonomy
Breed: Specific breeds affected (with VBO identifiers if applicable)

Search first: VBO (Vertebrate Breed Ontology)
Gene: Orthologous genes in other species (with NCBI Gene IDs)

Search first: NCBI Gene
Natural Disease:
Naturally occurring disease in other species (companion animals, wildlife) > Search first: OMIA (Online Mendelian Inheritance in Animals), VetCompass, PubMed
Veterinary relevance and importance in animal health > Search first: OMIA, veterinary databases, PubMed
Comparative Biology:
Comparative pathology (similarities and differences across species) > Search first: OMIA, comparative pathology databases, PubMed
Evolutionary conservation of disease mechanisms > Search first: HomoloGene, OrthoMCL, Alliance of Genome Resources
Transmission (if applicable):
Zoonotic potential > Search first: CDC zoonotic diseases, WHO zoonoses, GIDEON
Cross-species susceptibility > Search first: NCBI Taxonomy, veterinary databases, PubMed

15. Model Organisms

Model Types:
Model organism type (mammalian, invertebrate, cellular, in vitro) > Search first: Alliance of Genome Resources, model organism databases
Specific model systems (mouse, rat, zebrafish, Drosophila, C. elegans, yeast, cell lines, organoids, iPSCs) > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, SGD, ATCC, Cellosaurus
Induced models (drug treatment, surgical intervention, environmental manipulation) > Search first: MGI, model organism databases, PubMed
Genetic Models:
Types available (knockout, knock-in, transgenic, conditional, humanized) > Search first: MGI, IMPC, KOMP, EuMMCR, IMSR
Model Characteristics:
Phenotype recapitulation (how well model reproduces human disease features) > Search first: Model organism databases, comparative studies, PubMed
Model limitations (aspects of human disease not captured) > Search first: Model organism databases, PubMed, review articles
Applications:
Research applications (what aspects of disease can be studied) > Search first: Model organism databases, PubMed
Resources:
Model databases > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, IMSR, EMMA, MMRRC

Citation Requirements

Cite primary literature (PMID preferred) for all mechanistic and clinical claims
Prioritize recent reviews and landmark papers
Include direct quotes from abstracts where possible to support key statements
Distinguish evidence source types: human clinical, model organism, in vitro, computational

Output Format

Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease

This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details

Disease characteristics research report: IDH‑Mutant Astrocytoma

Target disease

Disease name: Astrocytoma, IDH‑mutant (adult-type diffuse glioma)
Category: Primary malignant brain tumor; adult-type diffuse glioma
MONDO ID: Not recovered from the provided sources in this run (requires ontology lookup outside the retrieved papers).

Executive overview (current understanding)

Astrocytoma, IDH‑mutant is an adult-type diffusely infiltrating glioma defined by an IDH1 or IDH2 hotspot mutation and the absence of whole-arm 1p/19q codeletion (which would instead define oligodendroglioma). WHO CNS5 (2021) integrates molecular findings into both classification and grading (grades 2–4), including the key change that CDKN2A/B homozygous deletion is sufficient for CNS WHO grade 4 assignment even in the absence of necrosis or microvascular proliferation. (antonelli2022adulttypediffuse pages 1-2, horbinski2022clinicalimplicationsof pages 4-5)

Topic	Key finding	Quantitative details	Source (year, URL)	Citation
WHO 2021 entity definition	Adult-type diffuse glioma entity is Astrocytoma, IDH-mutant; requires IDH1 or IDH2 mutation and absence of whole-arm 1p/19q codeletion.	WHO CNS5 recognizes grades 2, 3, and 4 within one molecularly defined entity.	Antonelli & Poliani, 2022, https://doi.org/10.32074/1591-951x-823	(antonelli2022adulttypediffuse pages 1-2, antonelli2022adulttypediffuse pages 2-4)
WHO 2021 grading: grade 2	Grade 2: diffusely infiltrating astrocytoma without brisk mitotic activity, necrosis, or microvascular proliferation.	Histology-based lower grade within IDH-mutant astrocytoma.	Galbraith et al., 2024, https://doi.org/10.1093/neuonc/noae009	(galbraith2024prognosticvalueof pages 1-2)
WHO 2021 grading: grade 3	Grade 3: increased mitotic activity/significant mitoses, but no necrosis or microvascular proliferation.	Practical pathology review notes mitotic rate ≥2–3 and Ki-67 up to ~10% associated with grade 3/worse survival.	Galbraith et al., 2024, https://doi.org/10.1093/neuonc/noae009; Antonelli & Poliani, 2022, https://doi.org/10.32074/1591-951x-823	(galbraith2024prognosticvalueof pages 1-2, antonelli2022adulttypediffuse pages 2-4)
WHO 2021 grading: grade 4	Grade 4: necrosis and/or microvascular proliferation or CDKN2A/B homozygous deletion, even if classic histologic grade-4 features are absent.	CDKN2A/B homozygous deletion is sufficient for CNS WHO grade 4 assignment.	Horbinski et al., 2022, https://doi.org/10.1038/s41582-022-00679-w; Reuss, 2023, https://doi.org/10.1007/s11060-023-04250-5	(horbinski2022clinicalimplicationsof pages 4-5, reuss2023updatesonthe pages 1-2)
Core molecular feature: IDH hotspots	Canonical hotspot mutations define the entity; IDH1 R132H is the dominant alteration, with rarer noncanonical IDH1/IDH2 variants.	IDH1 R132H present in >90% of cases by review; one genomic cohort found 96.8% IDH1 R132H, with rare R132S/R132G and IDH2 R172G (~1.1% each).	Antonelli & Poliani, 2022, https://doi.org/10.32074/1591-951x-823; Lee et al., 2023, https://doi.org/10.1038/s41598-023-32153-y	(antonelli2022adulttypediffuse pages 2-4, lee2023genomicprofilesof pages 5-7)
Core molecular feature: ATRX	ATRX loss/inactivation is typical and supports astrocytic lineage.	ATRX alterations in 82.1% of one 95-case cohort; ATRX mutation and ATRX loss by IHC were 100% concordant in that study.	Lee et al., 2023, https://doi.org/10.1038/s41598-023-32153-y	(lee2023genomicprofilesof pages 5-7, lee2023genomicprofilesof pages 1-2)
Core molecular feature: TP53	TP53 mutation is common and often co-occurs with ATRX alteration in IDH-mutant astrocytoma.	TP53 mutations in 86.3% of one 95-case cohort.	Lee et al., 2023, https://doi.org/10.1038/s41598-023-32153-y	(lee2023genomicprofilesof pages 5-7, lee2023genomicprofilesof pages 1-2)
Core molecular feature: 1p/19q status	Whole-arm 1p/19q codeletion must be absent; if present with IDH mutation, diagnosis shifts to oligodendroglioma.	In one astrocytoma cohort, true 1p/19q codeletion was rare (1.1%) and represented diagnostic confounding rather than typical biology.	Antonelli & Poliani, 2022, https://doi.org/10.32074/1591-951x-823; Lee et al., 2023, https://doi.org/10.1038/s41598-023-32153-y	(antonelli2022adulttypediffuse pages 4-6, lee2023genomicprofilesof pages 5-7)
Core molecular feature: MGMT promoter methylation	MGMT promoter methylation is common in IDH-mutant astrocytoma, though frequency varies by cohort.	Review: commonly observed; genomic cohort: 73.7% (70/95) overall.	Antonelli & Poliani, 2022, https://doi.org/10.32074/1591-951x-823; Lee et al., 2023, https://doi.org/10.1038/s41598-023-32153-y	(antonelli2022adulttypediffuse pages 2-4, lee2023genomicprofilesof pages 7-8)
Core molecular feature: G-CIMP	IDH mutation drives a glioma CpG island methylator phenotype (G-CIMP) / hypermethylated epigenetic state.	Qualitative hallmark; no single prevalence estimate reported in the extracted passages.	Antonelli & Poliani, 2022, https://doi.org/10.32074/1591-951x-823	(antonelli2022adulttypediffuse pages 2-4)
Additional adverse molecular markers	CDKN2A/B homozygous deletion is a major negative prognostic marker; MYCN amplification may identify especially poor-risk tumors.	CDKN2A/B homozygous deletion reported in about 22% overall in a review and 22.6% (14/95) in one cohort; MYCN amplification 6.5% (4/95) in one cohort.	Yuile et al., 2023, https://doi.org/10.3390/cimb45070335; Lee et al., 2023, https://doi.org/10.1038/s41598-023-32153-y	(yuile2023cdkn2abhomozygousdeletions pages 1-2, lee2023genomicprofilesof pages 7-8, lee2023genomicprofilesof pages 8-10)
Epidemiology: population-based incidence	Belgian registry reclassified adult diffuse gliomas in the molecular era; provides real-world incidence context but not a standalone incidence for all IDH-mutant astrocytoma grades combined.	Overall adult diffuse glioma ASR 8.55/100,000 person-years; grade 4 lesions 6.72/100,000; histologic astrocytoma grade 2 0.60/100,000 and grade 3 0.48/100,000. Full molecular status available in 67.1% of cases.	Pinson et al., 2024, https://doi.org/10.1093/neuonc/noad158	(pinson2024epidemiologyandsurvival pages 1-2, pinson2024epidemiologyandsurvival pages 3-4, pinson2024epidemiologyandsurvival pages 2-3)
Epidemiology: demographics	IDH-mutant astrocytoma tends to affect younger adults than IDH-wildtype glioblastoma.	Belgian registry median age: grade 2 37 y, grade 3 40 y; review source notes median age around ~40 y with slight male predominance.	Pinson et al., 2024, https://doi.org/10.1093/neuonc/noad158; Antonelli & Poliani, 2022, https://doi.org/10.32074/1591-951x-823	(pinson2024epidemiologyandsurvival pages 3-4, antonelli2022adulttypediffuse pages 2-4)
Survival: Belgian registry lower grades	Registry-based survival is favorable relative to IDH-wildtype disease.	3-year survival for IDH-mutant astrocytoma: grade 2 86.0%, grade 3 75.7%.	Pinson et al., 2024, https://doi.org/10.1093/neuonc/noad158	(pinson2024epidemiologyandsurvival pages 1-2)
Survival: Belgian registry grade 4	Molecularly defined grade 4 IDH-mutant astrocytoma has better survival than IDH-wildtype glioblastoma but remains aggressive.	Median OS 25.9 months; 3-year survival 40.1%. Comparator IDH-wildtype glioblastoma median OS 9.3 months.	Pinson et al., 2024, https://doi.org/10.1093/neuonc/noad158	(pinson2024epidemiologyandsurvival pages 3-4, pinson2024epidemiologyandsurvival pages 1-2)
Recent development: INDIGO / vorasidenib	Phase 3 INDIGO established benefit of the brain-penetrant mutant IDH1/2 inhibitor vorasidenib in residual/recurrent grade 2 IDH-mutant glioma after surgery.	Median PFS 27.7 vs 11.1 months for vorasidenib vs placebo; HR 0.39 (95% CI 0.27–0.56); time to next intervention HR 0.26; grade ≥3 ALT elevation 9.6% vs 0%.	Mellinghoff et al., 2023, https://doi.org/10.1056/NEJMoa2304194	(mellinghoff2023vorasidenibinidh1 pages 1-3, mellinghoff2023vorasidenibinidh1 media cdd01275)

Table: This table condenses the most actionable disease-characteristics evidence for Astrocytoma, IDH-mutant, including WHO 2021 grading, hallmark molecular features, key registry epidemiology/survival statistics, and the pivotal INDIGO vorasidenib result. It is useful as a compact reference for knowledge-base population and citation tracking.

1. Disease information

1.1 Definition and scope

WHO CNS5 (2021) adult-type diffuse glioma taxonomy: WHO CNS5 defines three adult-type diffuse gliomas: (i) Astrocytoma, IDH‑mutant; (ii) Oligodendroglioma, IDH‑mutant and 1p/19q‑codeleted; (iii) Glioblastoma, IDH‑wildtype. (antonelli2022adulttypediffuse pages 1-2, horbinski2022clinicalimplicationsof pages 4-5)
Entity definition: Astrocytoma, IDH‑mutant is characterized by an IDH1/2 mutation and lack of 1p/19q codeletion, and commonly shows TP53 and ATRX inactivation. (antonelli2022adulttypediffuse pages 2-4, antonelli2022adulttypediffuse pages 4-6)

1.2 Synonyms and alternative names

Common historical/clinical usage includes “diffuse astrocytoma (IDH‑mutant)”, “anaplastic astrocytoma (IDH‑mutant)”, and what was historically termed “IDH‑mutant glioblastoma”, now reclassified in WHO CNS5 as astrocytoma, IDH‑mutant, CNS WHO grade 4. (horbinski2022clinicalimplicationsof pages 4-5)

1.3 Derived from individual patients vs aggregated resources

The evidence summarized here is derived primarily from: - Aggregated, authoritative standards/reviews (e.g., Nature Reviews Neurology clinical implications of WHO CNS5). (horbinski2022clinicalimplicationsof pages 4-5) - Registry-based epidemiology (Belgian Cancer Registry reclassified to WHO 2021). (pinson2024epidemiologyandsurvival pages 1-2) - Clinical cohorts / institutional series and randomized clinical trials (e.g., INDIGO phase 3). (mellinghoff2023vorasidenibinidh1 pages 1-3)

2. Etiology

2.1 Causal factors (molecular drivers)

Somatic hotspot mutations in IDH1/IDH2 (most often IDH1 R132H) are early/defining driver events in this entity. (antonelli2022adulttypediffuse pages 2-4, lee2023genomicprofilesof pages 5-7)
Mutant IDH gains neomorphic enzymatic activity producing D‑2‑hydroxyglutarate (2‑HG), with downstream epigenetic effects (DNA/histone methylation changes) linked to altered differentiation programs. (carosi2024targetingisocitratedehydrogenase pages 4-6, gue2024the2021world pages 4-5)

2.2 Risk factors (host/environment)

The retrieved sources focus on molecular classification and treatment; they do not provide strong, quantified environmental or lifestyle risk factors specific to IDH‑mutant astrocytoma.

2.3 Protective factors / gene–environment interactions

Not established in the retrieved sources.

3. Phenotypes (clinical, imaging, pathology)

3.1 Typical clinical presentation

Clinical presentation is location-dependent (e.g., cortical involvement), and WHO CNS5 reviews emphasize that adult-type IDH‑mutant diffuse gliomas often present as grade 2–3 lesions and are typically supratentorial. (antonelli2022adulttypediffuse pages 1-2, antonelli2022adulttypediffuse pages 2-4)
Seizures are a common presenting feature in lower-grade diffuse gliomas in general; however, explicit frequency estimates for IDH‑mutant astrocytoma were not extracted from the retrieved texts in this run.

3.2 Imaging phenotypes

Reviews note that MRI often suggests lower grade (2–3) and that gadolinium enhancement can be associated with higher grade. (antonelli2022adulttypediffuse pages 1-2)
For WHO CNS5 radiology-oriented summaries, the T2–FLAIR mismatch sign is highlighted as supportive of IDH‑mutant astrocytoma in appropriate contexts (qualitative statement; no sensitivity/specificity extracted here). (gue2024the2021world pages 5-7)

3.3 Pathology (histology)

WHO CNS5 grading integrates histology with molecular findings. Histologic grade 4 features include necrosis and/or microvascular proliferation. (galbraith2024prognosticvalueof pages 1-2, horbinski2022clinicalimplicationsof pages 4-5)

3.4 Suggested HPO terms (examples; frequency not established in retrieved sources)

Because frequency-by-phenotype was not available in the retrieved sources, the following are suggested mappings commonly used for diffuse glioma symptom documentation: - Seizure: HP:0001250 - Headache: HP:0002315 - Focal neurological deficit (broad): HP:0001284 (or more specific terms per deficit) - Cognitive impairment: HP:0100543 - Increased intracranial pressure: HP:0002516

4. Genetic / molecular information

4.1 Causal/defining genes

IDH1, IDH2 (hotspot missense mutations; IDH1 R132H dominant). (antonelli2022adulttypediffuse pages 2-4, lee2023genomicprofilesof pages 5-7)

4.2 Highly recurrent cooperating alterations

ATRX alteration/loss and TP53 mutation are typical for IDH‑mutant astrocytoma and support astrocytic lineage vs oligodendroglioma. (antonelli2022adulttypediffuse pages 2-4, antonelli2022adulttypediffuse pages 4-6)
In a genomic cohort of 95 IDH‑mutant astrocytomas, TP53 mutations were 86.3% and ATRX alterations 82.1%. (lee2023genomicprofilesof pages 1-2, lee2023genomicprofilesof pages 5-7)

4.3 Key pathogenic variants (somatic)

IDH1/2 hotspots: IDH1 R132H dominant; rare noncanonical IDH1/IDH2 variants occur. In one cohort: IDH1 R132H 96.8%, with R132S, R132G, and IDH2 R172G each ~1.1%. (lee2023genomicprofilesof pages 5-7)

4.4 Chromosomal alterations and grading biomarker

CDKN2A/B homozygous deletion is now a WHO CNS5 molecular criterion sufficient for CNS WHO grade 4 assignment, even absent necrosis/microvascular proliferation. (horbinski2022clinicalimplicationsof pages 4-5, reuss2023updatesonthe pages 1-2)
Frequency examples:
Literature review: CDKN2A/B homozygous deletion reported in ~22% of IDH‑mutant astrocytomas. (yuile2023cdkn2abhomozygousdeletions pages 1-2)
A genomic cohort: 22.6% (14/95) had CDKN2A/2B homozygous deletion. (lee2023genomicprofilesof pages 7-8)

4.5 Epigenetics (DNA methylation; G‑CIMP) and methylation subtyping

IDH mutation is associated with a CpG island hypermethylation phenotype (often referred to as G‑CIMP). (antonelli2022adulttypediffuse pages 2-4)
DNA methylation profiling has an increasing clinical role in CNS5 and can support classification while also providing copy number information (e.g., for 1p/19q codeletion). (reuss2023updatesonthe pages 1-2)
In an NYU cohort (n=98) with validation (TCGA and Heidelberg), DNA methylation subclassification and CDKN2A/B homozygous deletion stratified overall survival, while histologic grade alone did not significantly stratify OS/PFS in that dataset (OS p=0.0016 and p=0.0286 respectively). (galbraith2024prognosticvalueof pages 1-2)

5. Environmental information

No specific environmental, lifestyle, or infectious causal factors were established from the retrieved sources.

6. Mechanism / pathophysiology

6.1 Causal chain (high-level)

Somatic IDH1/IDH2 hotspot mutation → neomorphic enzyme activity producing D‑2‑hydroxyglutarate (2‑HG). (gue2024the2021world pages 4-5)
2‑HG competitively inhibits α‑ketoglutarate–dependent dioxygenases (including TET and histone demethylases) → genome-wide epigenetic remodeling / hypermethylation programs (G‑CIMP). (gue2024the2021world pages 4-5, antonelli2022adulttypediffuse pages 2-4)
Epigenetic rewiring impacts differentiation programs and tumor cell states; accumulation of additional alterations (TP53, ATRX; and in aggressive cases CDKN2A/B homozygous deletion) drives malignant progression and worsened prognosis. (antonelli2022adulttypediffuse pages 2-4, horbinski2022clinicalimplicationsof pages 4-5)

6.2 Immune microenvironment and emerging multi-omics

The retrieved corpus included high-level discussion that IDH-mutant tumors are “epigenetically driven” and well-suited to single-cell/spatial multi-omics to resolve tumor–microenvironment interactions; however, detailed single-cell quantitative findings specific to IDH‑mutant astrocytoma were not captured in evidence snippets for 2023–2024 in this run. (laurengeleprince2024impactofd2hg pages 15-18)

6.3 Suggested ontology terms

GO Biological Process (examples): - DNA methylation or regulation of DNA methylation (e.g., DNA methylation, chromatin organization) - Regulation of cell cycle (relevant to CDKN2A/B loss)

Cell Ontology (CL) (examples): - Astrocyte (tumor lineage resemblance) - Oligodendrocyte progenitor cell (OPC)-like malignant states are frequently discussed in glioma literature; not quantified here - Microglia/macrophage (tumor-associated myeloid populations; not quantified here)

7. Anatomical structures affected

Primary site is the central nervous system (brain); adult-type diffuse gliomas are often supratentorial. (antonelli2022adulttypediffuse pages 2-4, antonelli2022adulttypediffuse pages 1-2)

UBERON suggestions (examples): - Brain: UBERON:0000955 - Cerebral cortex: UBERON:0000956 - Frontal lobe (if documented clinically): UBERON:0001870 (frontal lobe is mentioned as a predilection in a WHO CNS5 radiology-oriented review). (gue2024the2021world pages 4-5)

8. Temporal development

WHO CNS5 grades 2–4 represent a spectrum from lower-grade infiltrating disease (grade 2), increased mitotic activity (grade 3), to grade 4 behavior defined by necrosis/microvascular proliferation and/or CDKN2A/B homozygous deletion. (galbraith2024prognosticvalueof pages 1-2, horbinski2022clinicalimplicationsof pages 4-5)
Registry evidence indicates that for IDH‑mutant astrocytoma, histologic grade may be less prognostic than key molecular events (e.g., CDKN2A/B deletion; methylation subclass). (pinson2024epidemiologyandsurvival pages 1-2, galbraith2024prognosticvalueof pages 1-2)

9. Inheritance and population

9.1 Epidemiology (recent registry evidence prioritized)

Belgian Cancer Registry (2017–2019; reclassified to WHO 2021): - Full molecular status available in 67.1% of adult-type diffuse glioma cases. (pinson2024epidemiologyandsurvival pages 1-2) - For IDH‑mutant astrocytoma: - 3-year survival probability: grade 2 86.0%, grade 3 75.7%. (pinson2024epidemiologyandsurvival pages 1-2) - Grade 4 IDH‑mutant astrocytoma: median OS 25.9 months and 3-year survival 40.1%. (pinson2024epidemiologyandsurvival pages 3-4) - The registry reported overall adult diffuse glioma age-standardized incidence 8.55 per 100,000 person-years, and grade 4 lesions 6.72 per 100,000 person-years (not specific to IDH‑mutant astrocytoma alone). (pinson2024epidemiologyandsurvival pages 1-2)

9.2 Demographics

IDH‑mutant astrocytoma tends to present in younger adults than IDH‑wildtype glioblastoma; Belgian registry medians for IDH‑mutant astrocytoma were 37 years (grade 2) and 40 years (grade 3). (pinson2024epidemiologyandsurvival pages 3-4)

9.3 Inheritance

The retrieved sources do not establish a Mendelian inheritance pattern for IDH‑mutant astrocytoma as a disease entity; it is primarily driven by somatic alterations in tumor tissue.

10. Diagnostics

10.1 Standard integrated diagnostic workflow (WHO CNS5)

WHO CNS5 endorses integrated reporting: “Diagnostics should include different layers, namely histology, WHO grading and molecular findings.” (reuss2023updatesonthe pages 1-2)

Common first-line tests and methods (examples from WHO CNS5 diagnostic review and pathology guidance): - IDH1 R132H immunohistochemistry as routine screening; if negative in a suggestive case, proceed to IDH1/IDH2 sequencing for noncanonical variants. (antonelli2022adulttypediffuse pages 2-4) - ATRX immunohistochemistry (loss supports astrocytoma lineage) and p53 immunohistochemistry (strong/diffuse expression supports TP53 mutation, acknowledging limitations). (antonelli2022adulttypediffuse pages 2-4) - 1p/19q codeletion testing (FISH or molecular methods) to exclude oligodendroglioma. (antonelli2022adulttypediffuse pages 4-6) - CDKN2A/B status determination (commonly by FISH in some workflows; also inferable from copy-number derived from methylation arrays). (antonelli2022adulttypediffuse pages 4-6, reuss2023updatesonthe pages 1-2) - DNA methylation profiling: has “substantial” influence on WHO CNS5 and can provide both classification support and copy-number information (including 1p/19q). (reuss2023updatesonthe pages 1-2)

10.2 Differential diagnosis (high-level)

Oligodendroglioma (requires IDH mutation + whole-arm 1p/19q codeletion). (horbinski2022clinicalimplicationsof pages 4-5)
IDH-wildtype glioblastoma (molecularly defined by TERT promoter mutation, EGFR amplification, +7/−10 among other features; beyond scope here but included in WHO CNS5 guidance). (horbinski2022clinicalimplicationsof pages 4-5)

11. Outcome / prognosis

11.1 Prognostic molecular features

CDKN2A/B homozygous deletion is an adverse prognostic marker and a grade-4 defining criterion in WHO CNS5. (horbinski2022clinicalimplicationsof pages 4-5, yuile2023cdkn2abhomozygousdeletions pages 1-2)
DNA methylation subclassification can outperform histologic grade for OS stratification in institutional cohorts, and can separate IDH‑mutant astrocytomas into epigenetic risk groups. (galbraith2024prognosticvalueof pages 1-2)

11.2 Survival statistics (recent)

Belgian registry (WHO 2021 era): grade 4 IDH‑mutant astrocytoma median OS 25.9 months; grade 2–3 have high 3-year survival (86.0% and 75.7%). (pinson2024epidemiologyandsurvival pages 3-4, pinson2024epidemiologyandsurvival pages 1-2)

12. Treatment

12.1 Current applications and real-world implementations

Maximal safe resection is standard initial management. (laurengeleprince2024impactofd2hg pages 15-18)
WHO CNS5 clinical guidance recommends treating grade 4 IDH‑mutant astrocytoma with radiation therapy and temozolomide, analogously to IDH‑wildtype glioblastoma. (horbinski2022clinicalimplicationsof pages 4-5)

12.2 Evidence-based adjuvant therapy (grade 2)

SEOM‑GEINO grade 2 glioma guidelines (published 2024; based on 2023 guideline process): - Early RT improves PFS: EORTC 22845 median PFS 5.3 vs 3.4 years, OS ~7.4 years in both arms. (vazsalgado2024seomgeinoclinicalguidelines pages 4-5) - RT followed by PCV is recommended for high-risk grade 2 patients; RTOG 9802: RT+PCV OS 13.3 vs 7.8 years (HR 0.59, p=0.003). (vazsalgado2024seomgeinoclinicalguidelines pages 4-5)

12.3 Key recent development (2023): targeted IDH inhibition (vorasidenib)

INDIGO phase 3 trial (NEJM; publication date Aug 2023; URL https://doi.org/10.1056/NEJMoa2304194): - Abstract quote (efficacy): “Progression-free survival was significantly improved in the vorasidenib group as compared with the placebo group (median progression-free survival, 27.7 months vs. 11.1 months; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.27 to 0.56; P<0.001).” (mellinghoff2023vorasidenibinidh1 pages 1-3) - Abstract quote (safety): “An increased alanine aminotransferase level of grade 3 or higher occurred in 9.6% of the patients who received vorasidenib and in no patients who received placebo.” (mellinghoff2023vorasidenibinidh1 pages 1-3) - Figure/table evidence for key endpoints and ALT: median PFS 27.7 vs 11.1 months, HR 0.39; ALT increase grade ≥3 9.6% vs 0%. (mellinghoff2023vorasidenibinidh1 media cdd01275)

12.4 MAXO term suggestions (examples)

Surgical tumor resection: MAXO:0000445 (surgical excision; placeholder—exact MAXO mapping should be validated)
Radiotherapy: MAXO:0000127 (radiation therapy; placeholder)
Temozolomide chemotherapy: MAXO:0000647 (antineoplastic drug therapy; placeholder)
Targeted therapy with IDH inhibitor (vorasidenib): MAXO:0000058 (targeted therapy; placeholder)

Note: MAXO IDs above are suggestions and should be verified against the MAXO ontology.

13. Prevention

No established primary prevention strategies were identified in the retrieved sources. For most diffuse gliomas, primary prevention is limited; secondary prevention generally involves prompt evaluation of symptoms and imaging rather than population screening.

14. Other species / natural disease

Not addressed in the retrieved sources.

15. Model organisms

Not addressed in the retrieved sources collected in this run (no specific GEMMs, PDX, or organoid papers were retrieved/extracted as evidence).

Expert opinions and authoritative analysis (selected)

WHO CNS5 clinical implications review emphasizes that the updated molecularly integrated classification has direct therapeutic implications, including the grade 4 assignment based on CDKN2A/B deletion and the recommendation to treat grade 4 IDH‑mutant astrocytoma similarly to glioblastoma. (horbinski2022clinicalimplicationsof pages 4-5)
WHO diagnostic updates underscore the need for integrated diagnostics and state that DNA methylation profiling substantially influences WHO CNS5 and can provide both classification and copy-number information. (reuss2023updatesonthe pages 1-2)

Limitations of this run (evidence completeness)

PMIDs were not available in the evidence snippets returned by the tools for many key sources (NEJM/Nature Reviews/Neuro-Oncology), so this report cites DOIs/URLs and publication months/years as available in the retrieved bibliographic records.
Several requested areas (protective/environmental factors, phenotype frequencies/QoL metrics, model organisms) were not covered by the retrieved evidence in this tool run and would require additional targeted retrieval.

References

(antonelli2022adulttypediffuse pages 1-2): Manila Antonelli and Pietro Luigi Poliani. Adult type diffuse gliomas in the new 2021 who classification. Pathologica, 114:397-409, Dec 2022. URL: https://doi.org/10.32074/1591-951x-823, doi:10.32074/1591-951x-823. This article has 67 citations.
(horbinski2022clinicalimplicationsof pages 4-5): Craig Horbinski, Tamar Berger, Roger J. Packer, and Patrick Y. Wen. Clinical implications of the 2021 edition of the who classification of central nervous system tumours. Nature Reviews Neurology, 18:515-529, Jun 2022. URL: https://doi.org/10.1038/s41582-022-00679-w, doi:10.1038/s41582-022-00679-w. This article has 334 citations and is from a highest quality peer-reviewed journal.
(antonelli2022adulttypediffuse pages 2-4): Manila Antonelli and Pietro Luigi Poliani. Adult type diffuse gliomas in the new 2021 who classification. Pathologica, 114:397-409, Dec 2022. URL: https://doi.org/10.32074/1591-951x-823, doi:10.32074/1591-951x-823. This article has 67 citations.
(galbraith2024prognosticvalueof pages 1-2): Kristyn Galbraith, Mekka Garcia, Siyu Wei, Anna Chen, Chanel Schroff, Jonathan Serrano, Donato Pacione, Dimitris G Placantonakis, Christopher M William, Arline Faustin, David Zagzag, Marissa Barbaro, Maria Del Pilar Guillermo Prieto Eibl, Mitsuaki Shirahata, David Reuss, Quynh T Tran, Zahangir Alom, Andreas von Deimling, Brent A Orr, Erik P Sulman, John G Golfinos, Daniel A Orringer, Rajan Jain, Evan Lieberman, Yang Feng, and Matija Snuderl. Prognostic value of dna methylation subclassification, aneuploidy, and cdkn2a/b homozygous deletion in predicting clinical outcome of idh mutant astrocytomas. Neuro-oncology, 26:1042-1051, Jan 2024. URL: https://doi.org/10.1093/neuonc/noae009, doi:10.1093/neuonc/noae009. This article has 15 citations and is from a domain leading peer-reviewed journal.
(reuss2023updatesonthe pages 1-2): David.E. Reuss. Updates on the who diagnosis of idh-mutant glioma. Journal of Neuro-Oncology, 162:461-469, Jan 2023. URL: https://doi.org/10.1007/s11060-023-04250-5, doi:10.1007/s11060-023-04250-5. This article has 73 citations and is from a peer-reviewed journal.
(lee2023genomicprofilesof pages 5-7): Kwanghoon Lee, Seong-Ik Kim, Eric Eunshik Kim, Yu-Mi Shim, Jae-Kyung Won, Chul-Kee Park, Seung Hong Choi, Hongseok Yun, Hyunju Lee, and Sung-Hye Park. Genomic profiles of idh-mutant gliomas: mycn-amplified idh-mutant astrocytoma had the worst prognosis. Scientific Reports, Apr 2023. URL: https://doi.org/10.1038/s41598-023-32153-y, doi:10.1038/s41598-023-32153-y. This article has 23 citations and is from a peer-reviewed journal.
(lee2023genomicprofilesof pages 1-2): Kwanghoon Lee, Seong-Ik Kim, Eric Eunshik Kim, Yu-Mi Shim, Jae-Kyung Won, Chul-Kee Park, Seung Hong Choi, Hongseok Yun, Hyunju Lee, and Sung-Hye Park. Genomic profiles of idh-mutant gliomas: mycn-amplified idh-mutant astrocytoma had the worst prognosis. Scientific Reports, Apr 2023. URL: https://doi.org/10.1038/s41598-023-32153-y, doi:10.1038/s41598-023-32153-y. This article has 23 citations and is from a peer-reviewed journal.
(antonelli2022adulttypediffuse pages 4-6): Manila Antonelli and Pietro Luigi Poliani. Adult type diffuse gliomas in the new 2021 who classification. Pathologica, 114:397-409, Dec 2022. URL: https://doi.org/10.32074/1591-951x-823, doi:10.32074/1591-951x-823. This article has 67 citations.
(lee2023genomicprofilesof pages 7-8): Kwanghoon Lee, Seong-Ik Kim, Eric Eunshik Kim, Yu-Mi Shim, Jae-Kyung Won, Chul-Kee Park, Seung Hong Choi, Hongseok Yun, Hyunju Lee, and Sung-Hye Park. Genomic profiles of idh-mutant gliomas: mycn-amplified idh-mutant astrocytoma had the worst prognosis. Scientific Reports, Apr 2023. URL: https://doi.org/10.1038/s41598-023-32153-y, doi:10.1038/s41598-023-32153-y. This article has 23 citations and is from a peer-reviewed journal.
(yuile2023cdkn2abhomozygousdeletions pages 1-2): Alexander Yuile, Laveniya Satgunaseelan, Joe Q. Wei, Michael Rodriguez, Michael Back, Nick Pavlakis, Amanda Hudson, Marina Kastelan, Helen R. Wheeler, and Adrian Lee. Cdkn2a/b homozygous deletions in astrocytomas: a literature review. Current Issues in Molecular Biology, 45:5276-5292, Jun 2023. URL: https://doi.org/10.3390/cimb45070335, doi:10.3390/cimb45070335. This article has 34 citations.
(lee2023genomicprofilesof pages 8-10): Kwanghoon Lee, Seong-Ik Kim, Eric Eunshik Kim, Yu-Mi Shim, Jae-Kyung Won, Chul-Kee Park, Seung Hong Choi, Hongseok Yun, Hyunju Lee, and Sung-Hye Park. Genomic profiles of idh-mutant gliomas: mycn-amplified idh-mutant astrocytoma had the worst prognosis. Scientific Reports, Apr 2023. URL: https://doi.org/10.1038/s41598-023-32153-y, doi:10.1038/s41598-023-32153-y. This article has 23 citations and is from a peer-reviewed journal.
(pinson2024epidemiologyandsurvival pages 1-2): Harry Pinson, Geert Silversmit, Dimitri Vanhauwaert, Katrijn Vanschoenbeek, Jean-Pierre Kalala Okito, Steven De Vleeschouwer, Tom Boterberg, and Cindy De Gendt. Epidemiology and survival of adult-type diffuse glioma in belgium during the molecular era. Neuro-oncology, 26:191-202, Aug 2024. URL: https://doi.org/10.1093/neuonc/noad158, doi:10.1093/neuonc/noad158. This article has 25 citations and is from a domain leading peer-reviewed journal.
(pinson2024epidemiologyandsurvival pages 3-4): Harry Pinson, Geert Silversmit, Dimitri Vanhauwaert, Katrijn Vanschoenbeek, Jean-Pierre Kalala Okito, Steven De Vleeschouwer, Tom Boterberg, and Cindy De Gendt. Epidemiology and survival of adult-type diffuse glioma in belgium during the molecular era. Neuro-oncology, 26:191-202, Aug 2024. URL: https://doi.org/10.1093/neuonc/noad158, doi:10.1093/neuonc/noad158. This article has 25 citations and is from a domain leading peer-reviewed journal.
(pinson2024epidemiologyandsurvival pages 2-3): Harry Pinson, Geert Silversmit, Dimitri Vanhauwaert, Katrijn Vanschoenbeek, Jean-Pierre Kalala Okito, Steven De Vleeschouwer, Tom Boterberg, and Cindy De Gendt. Epidemiology and survival of adult-type diffuse glioma in belgium during the molecular era. Neuro-oncology, 26:191-202, Aug 2024. URL: https://doi.org/10.1093/neuonc/noad158, doi:10.1093/neuonc/noad158. This article has 25 citations and is from a domain leading peer-reviewed journal.
(mellinghoff2023vorasidenibinidh1 pages 1-3): Ingo K. Mellinghoff, Martin J. van den Bent, Deborah T. Blumenthal, Mehdi Touat, Katherine B. Peters, Jennifer Clarke, Joe Mendez, Shlomit Yust-Katz, Liam Welsh, Warren P. Mason, François Ducray, Yoshie Umemura, Burt Nabors, Matthias Holdhoff, Andreas F. Hottinger, Yoshiki Arakawa, Juan M. Sepulveda, Wolfgang Wick, Riccardo Soffietti, James R. Perry, Pierre Giglio, Macarena de la Fuente, Elizabeth A. Maher, Steven Schoenfeld, Dan Zhao, Shuchi S. Pandya, Lori Steelman, Islam Hassan, Patrick Y. Wen, and Timothy F. Cloughesy. Vorasidenib in idh1- or idh2-mutant low-grade glioma. New England Journal of Medicine, 389:589-601, Aug 2023. URL: https://doi.org/10.1056/nejmoa2304194, doi:10.1056/nejmoa2304194. This article has 772 citations and is from a highest quality peer-reviewed journal.
(mellinghoff2023vorasidenibinidh1 media cdd01275): Ingo K. Mellinghoff, Martin J. van den Bent, Deborah T. Blumenthal, Mehdi Touat, Katherine B. Peters, Jennifer Clarke, Joe Mendez, Shlomit Yust-Katz, Liam Welsh, Warren P. Mason, François Ducray, Yoshie Umemura, Burt Nabors, Matthias Holdhoff, Andreas F. Hottinger, Yoshiki Arakawa, Juan M. Sepulveda, Wolfgang Wick, Riccardo Soffietti, James R. Perry, Pierre Giglio, Macarena de la Fuente, Elizabeth A. Maher, Steven Schoenfeld, Dan Zhao, Shuchi S. Pandya, Lori Steelman, Islam Hassan, Patrick Y. Wen, and Timothy F. Cloughesy. Vorasidenib in idh1- or idh2-mutant low-grade glioma. New England Journal of Medicine, 389:589-601, Aug 2023. URL: https://doi.org/10.1056/nejmoa2304194, doi:10.1056/nejmoa2304194. This article has 772 citations and is from a highest quality peer-reviewed journal.
(carosi2024targetingisocitratedehydrogenase pages 4-6): Francesca Carosi, Elisabetta Broseghini, Laura Fabbri, Giacomo Corradi, Riccardo Gili, Valentina Forte, Roberta Roncarati, Daria Maria Filippini, and Manuela Ferracin. Targeting isocitrate dehydrogenase (idh) in solid tumors: current evidence and future perspectives. Cancers, 16:2752, Aug 2024. URL: https://doi.org/10.3390/cancers16152752, doi:10.3390/cancers16152752. This article has 27 citations.
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(gue2024the2021world pages 5-7): Racine Gue and Dhairya A. Lakhani. The 2021 world health organization central nervous system tumor classification: the spectrum of diffuse gliomas. Biomedicines, 12:1349, Jun 2024. URL: https://doi.org/10.3390/biomedicines12061349, doi:10.3390/biomedicines12061349. This article has 13 citations.
(laurengeleprince2024impactofd2hg pages 15-18): A Laurenge-Leprince. Impact of d-2hg on the tumor microenvironment of idh-mutated gliomas. Unknown journal, 2024.
(vazsalgado2024seomgeinoclinicalguidelines pages 4-5): María Ángeles Vaz-Salgado, Belén Cigarral García, Isaura Fernández Pérez, Beatriz Jiménez Munárriz, Paula Sampedro Domarco, Ainhoa Hernández González, María Vieito Villar, Raquel Luque Caro, María Luisa Villamayor Delgado, and Juan Manuel Sepúlveda Sánchez. Seom-geino clinical guidelines for grade 2 gliomas (2023). Clinical and Translational Oncology, 26:2856-2865, Apr 2024. URL: https://doi.org/10.1007/s12094-024-03456-x, doi:10.1007/s12094-024-03456-x. This article has 4 citations and is from a peer-reviewed journal.

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Classifications

Subtypes

Pathophysiology

Histopathology

Pathograph

Phenotypes

Genetic Associations

Treatments

Biochemical Markers

Source YAML

References & Deep Research

References

Deep Research

Disease Characteristics Research Template

Target Disease

Research Objectives

1. Disease Information

2. Etiology

3. Phenotypes

4. Genetic/Molecular Information

5. Environmental Information

6. Mechanism / Pathophysiology

7. Anatomical Structures Affected

8. Temporal Development

9. Inheritance and Population

10. Diagnostics

11. Outcome/Prognosis

12. Treatment

13. Prevention

14. Other Species / Natural Disease

15. Model Organisms

Citation Requirements

Output Format

Disease characteristics research report: IDH‑Mutant Astrocytoma

Target disease

Executive overview (current understanding)

1. Disease information

1.1 Definition and scope

1.2 Synonyms and alternative names

1.3 Derived from individual patients vs aggregated resources

2. Etiology

2.1 Causal factors (molecular drivers)

2.2 Risk factors (host/environment)

2.3 Protective factors / gene–environment interactions

3. Phenotypes (clinical, imaging, pathology)

3.1 Typical clinical presentation

3.2 Imaging phenotypes

3.3 Pathology (histology)

3.4 Suggested HPO terms (examples; frequency not established in retrieved sources)

4. Genetic / molecular information

4.1 Causal/defining genes

4.2 Highly recurrent cooperating alterations

4.3 Key pathogenic variants (somatic)

4.4 Chromosomal alterations and grading biomarker

4.5 Epigenetics (DNA methylation; G‑CIMP) and methylation subtyping

5. Environmental information

6. Mechanism / pathophysiology

6.1 Causal chain (high-level)

6.2 Immune microenvironment and emerging multi-omics

6.3 Suggested ontology terms

7. Anatomical structures affected

8. Temporal development

9. Inheritance and population

9.1 Epidemiology (recent registry evidence prioritized)

9.2 Demographics

9.3 Inheritance

10. Diagnostics

10.1 Standard integrated diagnostic workflow (WHO CNS5)

10.2 Differential diagnosis (high-level)

11. Outcome / prognosis

11.1 Prognostic molecular features

11.2 Survival statistics (recent)

12. Treatment

12.1 Current applications and real-world implementations

12.2 Evidence-based adjuvant therapy (grade 2)

12.3 Key recent development (2023): targeted IDH inhibition (vorasidenib)

12.4 MAXO term suggestions (examples)

13. Prevention