Medulloblastoma

MONDO:0007959 Show in embeddings browser

Medulloblastoma is an embryonal, malignant brain tumor that arises in the cerebellum and is the most common malignant pediatric posterior-fossa tumor. WHO CNS5 (2021) classifies medulloblastoma along two parallel axes. The **molecularly defined** axis recognises four entities: WNT-activated; SHH-activated and TP53-wildtype; SHH-activated and TP53-mutant (split into two separate entities because TP53 status carries markedly different prognosis); and non-WNT/non-SHH. The historical transcriptional Groups 3 and 4 are retained under WHO 2021 as *provisional subtypes within non-WNT/non-SHH* rather than as top-level groups, alongside a set of provisional methylation subtypes. A parallel **histologically defined** axis recognises classic, desmoplastic/nodular, medulloblastoma with extensive nodularity (MBEN), and large-cell/anaplastic morphology, which retain independent prognostic weight. These groups differ in developmental cell of origin, driver alterations, age distribution, metastatic propensity, and prognosis. All share a posterior-fossa location, derivation from cerebellar/rhombic-lip progenitor populations, and a clinical syndrome dominated by raised intracranial pressure (headache, vomiting) and cerebellar dysfunction (ataxia). Standard care for children >3 years is maximal-safe resection followed by craniospinal irradiation and multi-agent chemotherapy; subgroup-specific de-escalation and targeted-therapy strategies (e.g., SHH-pathway inhibitors, WNT-subgroup radiation reduction) are active areas of investigation. Subgroup-specific molecular detail is curated in separate dismech entries (e.g., `Medulloblastoma_WNT_Activated`, `Medulloblastoma_SHH_Activated`); Group 3 and Group 4 are not yet curated.

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1
Pathophys.
5
Phenotypes
3
Medical Actions
5
Subtypes
6
Datasets
1
Deep Research
🏷

Classifications

ICD-O Morphology
Embryonal Neoplasm
Harrison's Part
ONCOLOGY HEMATOLOGY
◆

Subtypes

5
WNT-Activated Medulloblastoma
Approximately 10% of medulloblastomas. Driven by CTNNB1 exon 3 mutations or germline APC mutations. Best prognosis (>95% long-term survival); candidate for treatment de-escalation. Curated as `Medulloblastoma_WNT_Activated`.
SHH-Activated Medulloblastoma
Approximately 30% of medulloblastomas. Driven by PTCH1/SMO/SUFU loss or GLI2/MYCN amplification. WHO 2021 splits this group into two distinct entities by TP53 status — SHH-activated and TP53-wildtype, and SHH-activated and TP53-mutant — because TP53-mutant tumours carry a markedly worse prognosis and are enriched for Li-Fraumeni syndrome. Bimodal age distribution (infants and adults). Curated as `Medulloblastoma_SHH_Activated`.
Non-WNT/Non-SHH
The fourth WHO 2021 molecularly defined entity, accounting for roughly 60% of medulloblastomas and encompassing the historical transcriptional Groups 3 and 4, which WHO 2021 retains as provisional subtypes rather than separate entities. Not yet curated as a separate dismech entry.
Group 3
A provisional subtype within non-WNT/non-SHH under WHO 2021, not a top-level entity. Approximately 25% of medulloblastomas. MYC amplification is common; high metastatic rate and worst prognosis. Not yet curated as a separate dismech entry.
Group 4
A provisional subtype within non-WNT/non-SHH under WHO 2021, not a top-level entity. The most common single transcriptional group (approximately 35% of medulloblastomas). Heterogeneous drivers including MYCN amplification and SNCAIP duplication; intermediate prognosis. Not yet curated as a separate dismech entry.
⚙

Pathophysiology

1
Cerebellar Progenitor Proliferation
All molecular subgroups arise from progenitor populations of the developing cerebellum and rhombic lip, and converge on dysregulated proliferation, but they do not share a single cell of origin. SHH tumors derive from external-granule-layer granule-neuron precursors; WNT tumors from lower-rhombic-lip / dorsal brainstem progenitors; and Group 3 and Group 4 (non-WNT/non-SHH) tumors from rhombic-lip-derived progenitors, with Group 4 in particular linked to the unipolar brush cell lineage. The subgroup-specific oncogenic pathways (WNT/beta-catenin, Sonic Hedgehog, MYC-driven programs) feed a common proliferative phenotype across these distinct progenitor lineages. Cell Ontology currently has no class for unipolar brush cells or rhombic-lip progenitors, so the non-SHH lineages are bound to the generic neural progenitor cell class.
cerebellar granule neuron precursor (SHH subgroup cell of origin) CL:0002362 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves cerebellar granule neuron precursor (SHH subgroup cell of origin), annotated with cerebellar granule cell precursor (CL:0002362). CL:0002362 is a cell type from the Cell Ontology. rhombic lip-derived progenitor (WNT and non-WNT/non-SHH cell of origin) CL:0011020 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves rhombic lip-derived progenitor (WNT and non-WNT/non-SHH cell of origin), annotated with neural progenitor cell (CL:0011020). CL:0011020 is a cell type from the Cell Ontology.
cell population proliferation GO:0008283 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased cell population proliferation (GO:0008283). GO:0008283 is a biological process from the Gene Ontology. ↑ INCREASED cerebellum development GO:0021549 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal cerebellum development (GO:0021549). GO:0021549 is a biological process from the Gene Ontology. ⚠ ABNORMAL
cerebellum UBERON:0002037 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in cerebellum (UBERON:0002037). UBERON:0002037 is an anatomical location from the Uberon multi-species anatomy ontology. rhombic lip UBERON:0006215 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in rhombic lip (UBERON:0006215). UBERON:0006215 is an anatomical location from the Uberon multi-species anatomy ontology.
Show evidence (1 reference)
PMID:35489737 SUPPORT Human Clinical
"Medulloblastoma (MB) is the most common malignant pediatric posterior fossa"
Establishes medulloblastoma as the most common malignant pediatric posterior-fossa tumor, anchoring the cerebellar-progenitor framing of the disease.
●

Phenotypes

5
Digestive 1
Vomiting HP:0002013 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Vomiting (HP:0002013). HP:0002013 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:8756384 SUPPORT Human Clinical
"The most common presenting symptoms were vomiting (67%), headache (60%), ataxia (40%), and nausea (39%)."
In a cohort of 72 histologically proven medulloblastoma patients, vomiting was the single most common presenting symptom (67%), supporting vomiting as a hallmark presenting feature of medulloblastoma.
Eye 1
Papilledema HP:0001085 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Papilledema (HP:0001085). HP:0001085 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:34055437 SUPPORT Human Clinical
"Papilledema, ophthalmoparesis, and nystagmus were the most frequent ophthalmological signs."
In a study of pediatric intracranial tumours (with medulloblastoma among the most frequent histopathological diagnoses), papilledema was the most frequent ophthalmological sign, supporting papilledema from raised intracranial pressure as a presenting sign of medulloblastoma.
Head and Neck 1
Macrocephaly HP:0000256 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Macrocephaly (HP:0000256). HP:0000256 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:22120270 SUPPORT Human Clinical
"Children most often presented with a bulging fontanelle, hydrocephalus, or macrocephaly (seven patients)."
In a surgical series of infant brain tumors that included primitive neuroectodermal tumor/medulloblastoma, macrocephaly (with bulging fontanelle and hydrocephalus) was the most common presenting sign, supporting macrocephaly from CSF obstruction as a presenting feature of medulloblastoma in young infants.
Nervous System 2
Headache HP:0002315 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Headache (HP:0002315). HP:0002315 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:8756384 SUPPORT Human Clinical
"The most common presenting symptoms were vomiting (67%), headache (60%), ataxia (40%), and nausea (39%)."
In a cohort of 72 histologically proven medulloblastoma patients, headache was a presenting symptom in 60%, supporting headache as a common presenting feature of medulloblastoma.
Ataxia HP:0001251 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Ataxia (HP:0001251). HP:0001251 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:8756384 SUPPORT Human Clinical
"The most common presenting symptoms were vomiting (67%), headache (60%), ataxia (40%), and nausea (39%)."
In a cohort of 72 histologically proven medulloblastoma patients, ataxia was a presenting symptom in 40%, supporting cerebellar ataxia as a common presenting feature of medulloblastoma.
💊

Medical Actions

3
Surgical Resection
Action: Definitive Surgical ResectionNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Definitive Surgical Resection (NCIT:C154430). NCIT:C154430 is a clinical intervention from the NCI Thesaurus. NCIT:C154430
Maximal safe resection is the first-line treatment across molecular subgroups. Extent of resection is prognostic; near-total or gross-total resection is achievable in most cases.
Craniospinal Irradiation
Action: Craniospinal IrradiationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Craniospinal Irradiation (NCIT:C116437). NCIT:C116437 is a clinical intervention from the NCI Thesaurus. NCIT:C116437
Craniospinal irradiation (CSI) is standard for medulloblastoma due to the risk of leptomeningeal dissemination. CSI is generally avoided in children <3 years to limit neurocognitive late effects, and dose-reduction trials are exploring lower-intensity CSI for the favorable-prognosis WNT subgroup.
Chemotherapy
Action: ChemotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Chemotherapy (NCIT:C15632). NCIT:C15632 is a clinical intervention from the NCI Thesaurus. NCIT:C15632
Agent: cisplatin CHEBI:27899 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses cisplatin (CHEBI:27899). CHEBI:27899 is a therapeutic agent from Chemical Entities of Biological Interest. vincristine CHEBI:28445 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses vincristine (CHEBI:28445). CHEBI:28445 is a therapeutic agent from Chemical Entities of Biological Interest. cyclophosphamide CHEBI:4027 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses cyclophosphamide (CHEBI:4027). CHEBI:4027 is a therapeutic agent from Chemical Entities of Biological Interest. lomustine CHEBI:6520 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses lomustine (CHEBI:6520). CHEBI:6520 is a therapeutic agent from Chemical Entities of Biological Interest.
Multi-agent adjuvant chemotherapy is standard. In infants, intensive chemotherapy regimens are used to delay or avoid radiation; in the WNT subgroup, de-escalation trials are exploring reduced-intensity regimens.
📊

Related Datasets

6
Linking genes, genomic instability and molecular subgroups in medulloblastoma ega:EGAS00001000085
Brain tumors are the second most common pediatric cancer and carry the highest mortality rates in this age group. Medulloblastoma is the most frequent malignant brain tumor of childhood. Recent studies indicate that medulloblastoma comprises at least four sub-entities (SHH-signaling, WNT-signaling, Group-C, Group-D) that differ in molecular alterations, cell of origin, clinicopathological features and outcome. Further characterization of the entire spectrum of genomic alterations underlying the formation of these distinct groups is urgently needed to identify diagnostic and prognostic biomarkers for clinical management and uncover novel therapeutic targets.
human WGS
PMID:22265402
European Genome-phenome Archive study, matched because the disease is named in the study's own title ("Medulloblastoma"); description-level mentions were not accepted. EGA study_type: Whole Genome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.
Stratifying and Targeting Pediatric Medulloblastoma through Genomics ega:EGAS00001000273
In this project, genomic analyses of pediatric medulloblastoma samples, obtained through the international medulloblastoma consortium, will be performed. RNA and miRNA expression profiles of 1000 samples, representing all four subgroups (Wnt, Shh, Group C, and D), will be studied to identify novel subtypes within each subgroup. The resulting subtype-specific expression profiles will support the development of reliable and robust biomarkers to more accurately and reliably classify medulloblastomas for treatment in clinical trials. For that purpose, two assays will be developed: an antibody-based immunohistochemical assay and an orthogonal nucleic acid-based hybridization assay.
human
PMID:22832581
European Genome-phenome Archive study, matched because the disease is named in the study's own title ("Medulloblastoma"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.
Genetic landscape of pediatric Medulloblastoma ega:EGAS00001000347
Medulloblastoma is a heterogenous disease made up of at least four distinct subtypes of disease which appear to exploit and disrupt naturally occurring developmental pathways of cellular growth and hindbrain development. To better understand the driver mutations of this disease, we performed whole genome sequencing of 37 medulloblastomas and the corresponding normal DNA of the 37 affected children treated at St. Jude Children's Research Hospital. We have found several novel mutations which appear subtype specific. These mutations were checked for frequency in a separate tumor cohort of 56 children with medulloblastoma, also treated on the St.
human WGS
European Genome-phenome Archive study, matched because the disease is named in the study's own title ("Medulloblastoma"); description-level mentions were not accepted. EGA study_type: Whole Genome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.
Proteomics, post-translational modifications, and integrative analyses reveal heterogeneity of molecular mechanisms within medulloblastoma subgroups massive:MSV000082644
Archer TC, Ehrenberger T, Mundt F, Gold MP, Krug K, Mah CK, Mahoney EL, Daniel CJ, LeNail A, Ramamoorthy D, Mertins P, Mani DR, Zhang H, Gillette MA, Clauser K, Noble M, Tang LC, Francois JP, Silterra J, Jensen J, Tamayo P, Korshunov A, Pfister SM, Kool M, Northcott PA, Sears RC, Lipton JO, Carr SA, Mesirov JP, Pomeroy SL, Fraenkel E. Cancer Cell 2018. There is a pressing need to identify therapeutic targets in tumors with low mutation rates such as the malignant pediatric brain tumor medulloblastoma.
Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Medulloblastoma"). Retrieved 2026-08-02.
TAp73 is a marker of glutamine addiction in medulloblastoma metabolomics_workbench:ST000898
Located via OmicsDI, which aggregates across omics repositories; this record comes from metabolomics_workbench. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Medulloblastoma"). Retrieved 2026-08-02.
Sequencing of Medulloblastoma dbgap:phs000409
Medulloblastoma is a heterogenous disease made up of at least four distinct subtypes of disease which appear to exploit and disrupt naturally occurring developmental pathways of cellular growth and hindbrain development. To better understand the driver mutations of this disease, we performed whole genome sequencing of 37 medulloblastomas and the corresponding normal DNA of the 37 affected children treated at St. Jude Children's Research Hospital. We have found several novel mutations which appear subtype specific.
Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Medulloblastoma"). Retrieved 2026-08-02.
{ }

Source YAML

click to show 
name: Medulloblastoma
creation_date: '2026-05-12T00:00:00Z'
description: >-
  Medulloblastoma is an embryonal, malignant brain tumor that arises in the
  cerebellum and is the most common malignant pediatric posterior-fossa
  tumor. WHO CNS5 (2021) classifies medulloblastoma along two parallel axes.
  The **molecularly defined** axis recognises four entities: WNT-activated;
  SHH-activated and TP53-wildtype; SHH-activated and TP53-mutant (split into
  two separate entities because TP53 status carries markedly different
  prognosis); and non-WNT/non-SHH. The historical transcriptional Groups 3
  and 4 are retained under WHO 2021 as *provisional subtypes within
  non-WNT/non-SHH* rather than as top-level groups, alongside a set of
  provisional methylation subtypes. A parallel **histologically defined**
  axis recognises classic, desmoplastic/nodular, medulloblastoma with
  extensive nodularity (MBEN), and large-cell/anaplastic morphology, which
  retain independent prognostic weight. These groups differ in developmental
  cell of origin, driver alterations, age distribution, metastatic
  propensity, and prognosis. All share a posterior-fossa location,
  derivation from cerebellar/rhombic-lip progenitor populations, and a
  clinical syndrome dominated by raised intracranial pressure (headache,
  vomiting) and cerebellar dysfunction (ataxia). Standard care for children >3 years is
  maximal-safe resection followed by craniospinal irradiation and multi-agent
  chemotherapy; subgroup-specific de-escalation and targeted-therapy strategies
  (e.g., SHH-pathway inhibitors, WNT-subgroup radiation reduction) are active
  areas of investigation. Subgroup-specific molecular detail is curated in
  separate dismech entries (e.g., `Medulloblastoma_WNT_Activated`,
  `Medulloblastoma_SHH_Activated`); Group 3 and Group 4 are not yet curated.
categories:
- Central Nervous System Neoplasm
- Pediatric Brain Tumor
- Embryonal Tumor
- Molecularly Defined Tumor
has_subtypes:
- name: WNT
  display_name: WNT-Activated Medulloblastoma
  description: >-
    Approximately 10% of medulloblastomas. Driven by CTNNB1 exon 3 mutations
    or germline APC mutations. Best prognosis (>95% long-term survival);
    candidate for treatment de-escalation. Curated as
    `Medulloblastoma_WNT_Activated`.
- name: SHH
  display_name: SHH-Activated Medulloblastoma
  description: >-
    Approximately 30% of medulloblastomas. Driven by PTCH1/SMO/SUFU loss or
    GLI2/MYCN amplification. WHO 2021 splits this group into two distinct
    entities by TP53 status — SHH-activated and TP53-wildtype, and
    SHH-activated and TP53-mutant — because TP53-mutant tumours carry a
    markedly worse prognosis and are enriched for Li-Fraumeni syndrome.
    Bimodal age distribution (infants and adults). Curated as
    `Medulloblastoma_SHH_Activated`.
- name: Non-WNT/Non-SHH
  description: >-
    The fourth WHO 2021 molecularly defined entity, accounting for roughly
    60% of medulloblastomas and encompassing the historical transcriptional
    Groups 3 and 4, which WHO 2021 retains as provisional subtypes rather
    than separate entities. Not yet curated as a separate dismech entry.
- name: Group 3
  description: >-
    A provisional subtype within non-WNT/non-SHH under WHO 2021, not a
    top-level entity. Approximately 25% of medulloblastomas. MYC
    amplification is common; high metastatic rate and worst prognosis. Not
    yet curated as a separate dismech entry.
- name: Group 4
  description: >-
    A provisional subtype within non-WNT/non-SHH under WHO 2021, not a
    top-level entity. The most common single transcriptional group
    (approximately 35% of medulloblastomas). Heterogeneous drivers including
    MYCN amplification and SNCAIP duplication; intermediate prognosis. Not
    yet curated as a separate dismech entry.
pathophysiology:
- name: Cerebellar Progenitor Proliferation
  description: >-
    All molecular subgroups arise from progenitor populations of the
    developing cerebellum and rhombic lip, and converge on dysregulated
    proliferation, but they do not share a single cell of origin. SHH tumors
    derive from external-granule-layer granule-neuron precursors; WNT tumors
    from lower-rhombic-lip / dorsal brainstem progenitors; and Group 3 and
    Group 4 (non-WNT/non-SHH) tumors from rhombic-lip-derived progenitors,
    with Group 4 in particular linked to the unipolar brush cell lineage.
    The subgroup-specific oncogenic pathways (WNT/beta-catenin, Sonic
    Hedgehog, MYC-driven programs) feed a common proliferative phenotype
    across these distinct progenitor lineages. Cell Ontology currently has no
    class for unipolar brush cells or rhombic-lip progenitors, so the
    non-SHH lineages are bound to the generic neural progenitor cell class.
  evidence:
  - reference: PMID:35489737
    reference_title: "Molecular Stratification of Medulloblastoma: Clinical Outcomes and Therapeutic Interventions."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Medulloblastoma (MB) is the most common malignant pediatric posterior fossa"
    explanation: Establishes medulloblastoma as the most common malignant pediatric posterior-fossa tumor, anchoring the cerebellar-progenitor framing of the disease.
  cell_types:
  - preferred_term: cerebellar granule neuron precursor (SHH subgroup cell of origin)
    term:
      id: CL:0002362
      label: cerebellar granule cell precursor
  - preferred_term: rhombic lip-derived progenitor (WNT and non-WNT/non-SHH cell of origin)
    term:
      id: CL:0011020
      label: neural progenitor cell
  biological_processes:
  - preferred_term: cell population proliferation
    modifier: INCREASED
    term:
      id: GO:0008283
      label: cell population proliferation
  - preferred_term: cerebellum development
    modifier: ABNORMAL
    term:
      id: GO:0021549
      label: cerebellum development
  locations:
  - preferred_term: cerebellum
    term:
      id: UBERON:0002037
      label: cerebellum
  - preferred_term: rhombic lip
    term:
      id: UBERON:0006215
      label: rhombic lip
phenotypes:
- category: Neurological
  name: Headache
  description: >-
    Headache from increased intracranial pressure due to obstructive
    hydrocephalus, typically worse in the morning. Common at presentation
    across molecular subgroups.
  phenotype_term:
    preferred_term: Headache
    term:
      id: HP:0002315
      label: Headache
  evidence:
  - reference: PMID:8756384
    reference_title: "Is there a correlation between duration of presenting symptoms and stage of medulloblastoma at the time of diagnosis?"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The most common presenting symptoms were vomiting (67%), headache (60%), ataxia (40%), and nausea (39%)."
    explanation: In a cohort of 72 histologically proven medulloblastoma patients, headache was a presenting symptom in 60%, supporting headache as a common presenting feature of medulloblastoma.
- category: Neurological
  name: Ataxia
  description: >-
    Cerebellar ataxia reflecting tumor involvement of cerebellar structures;
    truncal with midline tumors, appendicular with lateral hemispheric tumors.
  phenotype_term:
    preferred_term: Ataxia
    term:
      id: HP:0001251
      label: Ataxia
  evidence:
  - reference: PMID:8756384
    reference_title: "Is there a correlation between duration of presenting symptoms and stage of medulloblastoma at the time of diagnosis?"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The most common presenting symptoms were vomiting (67%), headache (60%), ataxia (40%), and nausea (39%)."
    explanation: In a cohort of 72 histologically proven medulloblastoma patients, ataxia was a presenting symptom in 40%, supporting cerebellar ataxia as a common presenting feature of medulloblastoma.
- category: Neurological
  name: Vomiting
  description: >-
    Vomiting from raised intracranial pressure, characteristically in the
    morning; a common presenting symptom across subgroups.
  phenotype_term:
    preferred_term: Vomiting
    term:
      id: HP:0002013
      label: Vomiting
  evidence:
  - reference: PMID:8756384
    reference_title: "Is there a correlation between duration of presenting symptoms and stage of medulloblastoma at the time of diagnosis?"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The most common presenting symptoms were vomiting (67%), headache (60%), ataxia (40%), and nausea (39%)."
    explanation: In a cohort of 72 histologically proven medulloblastoma patients, vomiting was the single most common presenting symptom (67%), supporting vomiting as a hallmark presenting feature of medulloblastoma.
- category: Neurological
  name: Macrocephaly
  description: >-
    Increased head circumference in infants due to hydrocephalus from CSF
    obstruction; may be the presenting sign in young infants before other
    cerebellar signs emerge.
  phenotype_term:
    preferred_term: Macrocephaly
    term:
      id: HP:0000256
      label: Macrocephaly
  evidence:
  - reference: PMID:22120270
    reference_title: "Surgical treatment of brain tumors in infants younger than six months of age and review of the literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Children most often presented with a bulging fontanelle, hydrocephalus, or macrocephaly (seven patients)."
    explanation: In a surgical series of infant brain tumors that included primitive neuroectodermal tumor/medulloblastoma, macrocephaly (with bulging fontanelle and hydrocephalus) was the most common presenting sign, supporting macrocephaly from CSF obstruction as a presenting feature of medulloblastoma in young infants.
- category: Neurological
  name: Papilledema
  description: >-
    Optic-disc swelling from raised intracranial pressure; may produce
    visual symptoms if prolonged.
  phenotype_term:
    preferred_term: Papilledema
    term:
      id: HP:0001085
      label: Papilledema
  evidence:
  - reference: PMID:34055437
    reference_title: "Neuroophthalmic Manifestations of Intracranial Tumours in Children."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Papilledema, ophthalmoparesis, and nystagmus were the most frequent ophthalmological signs."
    explanation: In a study of pediatric intracranial tumours (with medulloblastoma among the most frequent histopathological diagnoses), papilledema was the most frequent ophthalmological sign, supporting papilledema from raised intracranial pressure as a presenting sign of medulloblastoma.
treatments:
- name: Surgical Resection
  description: >-
    Maximal safe resection is the first-line treatment across molecular
    subgroups. Extent of resection is prognostic; near-total or gross-total
    resection is achievable in most cases.
  therapeutic_modality: SURGERY
  treatment_term:
    preferred_term: Definitive Surgical Resection
    term:
      id: NCIT:C154430
      label: Definitive Surgical Resection
- name: Craniospinal Irradiation
  description: >-
    Craniospinal irradiation (CSI) is standard for medulloblastoma due to the
    risk of leptomeningeal dissemination. CSI is generally avoided in children
    <3 years to limit neurocognitive late effects, and dose-reduction trials
    are exploring lower-intensity CSI for the favorable-prognosis WNT
    subgroup.
  treatment_term:
    preferred_term: Craniospinal Irradiation
    term:
      id: NCIT:C116437
      label: Craniospinal Irradiation
- name: Chemotherapy
  description: >-
    Multi-agent adjuvant chemotherapy is standard. In infants, intensive
    chemotherapy regimens are used to delay or avoid radiation; in the WNT
    subgroup, de-escalation trials are exploring reduced-intensity regimens.
  treatment_term:
    preferred_term: Chemotherapy
    term:
      id: NCIT:C15632
      label: Chemotherapy
    therapeutic_agent:
    - preferred_term: cisplatin
      term:
        id: CHEBI:27899
        label: cisplatin
    - preferred_term: vincristine
      term:
        id: CHEBI:28445
        label: vincristine
    - preferred_term: cyclophosphamide
      term:
        id: CHEBI:4027
        label: cyclophosphamide
    - preferred_term: lomustine
      term:
        id: CHEBI:6520
        label: lomustine
notes: >-
  This entry is a parent / root-level dismech record for medulloblastoma
  organising the four molecular subgroups recognised under WHO 2021. Subgroup-
  specific pathophysiology, driver genetics, and subgroup-targeted therapy are
  curated in separate dismech files where available
  (`Medulloblastoma_WNT_Activated`, `Medulloblastoma_SHH_Activated`). Group 3
  and Group 4 entries are scoped as follow-up work.
disease_term:
  preferred_term: medulloblastoma
  term:
    id: MONDO:0007959
    label: medulloblastoma
classifications:
  icdo_morphology:
    classification_value: Embryonal Neoplasm
    notes: >-
      Derived from this entry's disease term MONDO:0007959 (medulloblastoma),
      which carries the cross-reference ICDO:9470/3 and whose NCIT
      cross-reference NCIT:C3222 (Medulloblastoma) is a descendant of
      NCIT:C3264 (Embryonal Neoplasm), the term this enum value is bound to.
      Medulloblastoma is a CNS embryonal tumour, so ``Glioma`` would be the
      wrong morphology axis despite its intracranial site.
  harrisons_chapter:
  - classification_value: ONCOLOGY_HEMATOLOGY
    notes: >-
      Medulloblastoma is managed as a CNS solid-tumor oncology problem
      (resection, craniospinal irradiation, cytotoxic chemotherapy).
datasets:
- accession: ega:EGAS00001000085
  title: Linking genes, genomic instability and molecular subgroups in medulloblastoma
  description: Brain tumors are the second most common pediatric cancer and carry the highest mortality rates in this age group. Medulloblastoma is the most frequent malignant brain tumor of childhood. Recent studies indicate that medulloblastoma comprises at least four sub-entities (SHH-signaling, WNT-signaling, Group-C, Group-D) that differ in molecular alterations, cell of origin, clinicopathological features and outcome. Further characterization of the entire spectrum of genomic alterations underlying the formation of these distinct groups is urgently needed to identify diagnostic and prognostic biomarkers for clinical management and uncover novel therapeutic targets.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: WGS
  publication: PMID:22265402
  notes: 'European Genome-phenome Archive study, matched because the disease is named in the study''s own title ("Medulloblastoma"); description-level mentions were not accepted. EGA study_type: Whole Genome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.'
- accession: ega:EGAS00001000273
  title: Stratifying and Targeting Pediatric Medulloblastoma through Genomics
  description: 'In this project, genomic analyses of pediatric medulloblastoma samples, obtained through the international medulloblastoma consortium, will be performed. RNA and miRNA expression profiles of 1000 samples, representing all four subgroups (Wnt, Shh, Group C, and D), will be studied to identify novel subtypes within each subgroup. The resulting subtype-specific expression profiles will support the development of reliable and robust biomarkers to more accurately and reliably classify medulloblastomas for treatment in clinical trials. For that purpose, two assays will be developed: an antibody-based immunohistochemical assay and an orthogonal nucleic acid-based hybridization assay.'
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  publication: PMID:22832581
  notes: 'European Genome-phenome Archive study, matched because the disease is named in the study''s own title ("Medulloblastoma"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.'
- accession: ega:EGAS00001000347
  title: Genetic landscape of pediatric Medulloblastoma
  description: Medulloblastoma is a heterogenous disease made up of at least four distinct subtypes of disease which appear to exploit and disrupt naturally occurring developmental pathways of cellular growth and hindbrain development. To better understand the driver mutations of this disease, we performed whole genome sequencing of 37 medulloblastomas and the corresponding normal DNA of the 37 affected children treated at St. Jude Children's Research Hospital. We have found several novel mutations which appear subtype specific. These mutations were checked for frequency in a separate tumor cohort of 56 children with medulloblastoma, also treated on the St.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: WGS
  notes: 'European Genome-phenome Archive study, matched because the disease is named in the study''s own title ("Medulloblastoma"); description-level mentions were not accepted. EGA study_type: Whole Genome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.'
- accession: massive:MSV000082644
  title: Proteomics, post-translational modifications, and integrative analyses reveal heterogeneity of molecular mechanisms within medulloblastoma subgroups
  description: 'Archer TC, Ehrenberger T, Mundt F, Gold MP, Krug K, Mah CK, Mahoney EL, Daniel CJ, LeNail A, Ramamoorthy D, Mertins P, Mani DR, Zhang H, Gillette MA, Clauser K, Noble M, Tang LC, Francois JP, Silterra J, Jensen J, Tamayo P, Korshunov A, Pfister SM, Kool M, Northcott PA, Sears RC, Lipton JO, Carr SA, Mesirov JP, Pomeroy SL, Fraenkel E. Cancer Cell 2018. There is a pressing need to identify therapeutic targets in tumors with low mutation rates such as the malignant pediatric brain tumor medulloblastoma.'
  notes: Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Medulloblastoma"). Retrieved 2026-08-02.
- accession: metabolomics_workbench:ST000898
  title: TAp73 is a marker of glutamine addiction in medulloblastoma
  notes: Located via OmicsDI, which aggregates across omics repositories; this record comes from metabolomics_workbench. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Medulloblastoma"). Retrieved 2026-08-02.
- accession: dbgap:phs000409
  title: Sequencing of Medulloblastoma
  description: ' Medulloblastoma is a heterogenous disease made up of at least four distinct subtypes of disease which appear to exploit and disrupt naturally occurring developmental pathways of cellular growth and hindbrain development. To better understand the driver mutations of this disease, we performed whole genome sequencing of 37 medulloblastomas and the corresponding normal DNA of the 37 affected children treated at St. Jude Children''s Research Hospital. We have found several novel mutations which appear subtype specific.'
  notes: Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Medulloblastoma"). Retrieved 2026-08-02.
📚

References & Deep Research

Deep Research

1
Medulloblastoma Deep Research Fallback ▸

Medulloblastoma Deep Research Fallback

Provider Attempts

No deep-research provider was invoked for this root-level entry. The two existing subgroup-specific dismech files (Medulloblastoma_WNT_Activated, Medulloblastoma_SHH_Activated) already have full deep-research artifacts in research/ from their own curation. This root entry was curated directly from the verified literature already cached in references_cache/ and shared by both subgroup files; no provider was re-run because the root scope only synthesises features that are shared across the four WHO 2021 molecular subgroups (WNT, SHH, Group 3, Group 4).

Integrated Literature Synthesis

Medulloblastoma (MONDO:0007959) is an embryonal, malignant brain tumor that arises in the cerebellum and is the most common malignant pediatric posterior-fossa tumor. PMID:35489737 ("Molecular Stratification of Medulloblastoma: Clinical Outcomes and Therapeutic Interventions") establishes that "Recent WHO (2021) guidelines stratified MB into four molecular subgroups with four and eight further subgroups for SHH and non-WNT/non-SHH MB, respectively." The four subgroups are listed via has_subtypes rather than as a pathophysiology node — per the reviewer feedback, classification logic belongs in has_subtypes and description, not in pathophysiology[].

Cellular origin / shared mechanism. Across subgroups, tumors derive from cerebellar progenitor populations and converge on dysregulated proliferation in the developing cerebellum (CL:0001031 cerebellar granule cell, GO:0008283 cell-population proliferation INCREASED, GO:0021549 cerebellum development ABNORMAL, UBERON:0002037 cerebellum). WNT tumors derive from lower-rhombic-lip progenitors; SHH tumors from external-granule-layer granule-neuron precursors. The subgroup-specific oncogenic pathways (WNT/beta-catenin, Sonic Hedgehog, MYC-driven programs) feed this common proliferative endpoint — the single shared pathophysiology node curated here.

Clinical syndrome. Five HP-bound phenotypes are captured without frequency: tags (Headache HP:0002315, Ataxia HP:0001251, Vomiting HP:0002013, Macrocephaly HP:0000256, Papilledema HP:0001085). Per the PR review the frequency tags were removed because no quantitative cohort evidence was cited in scope to support specific frequency bands; reintroduce per the frequency-evidence SOP once subgroup-pooled clinical-cohort data are curated.

Management. Three modalities of standard care across subgroups: - Surgical resection (MAXO:0000004). - Craniospinal irradiation (MAXO:0000014), generally avoided in children <3 years to limit neurocognitive late effects. - Multi-agent chemotherapy (MAXO:0000647) with cisplatin (CHEBI:27899), vincristine (CHEBI:28445), cyclophosphamide (CHEBI:4027), and lomustine (CHEBI:6520) as the canonical agents (added in response to PR review).

Out of scope for the root entry

  • The previously-included histopathology block has been removed because it relied on NCIT:C3222 (the disease) as the finding_term and evidenced an epidemiological claim, not a pathologist-level histological finding. True histology (densely packed small blue round cells, Homer Wright rosettes, desmoplastic-nodular vs anaplastic large-cell morphology, synaptophysin expression) belongs in subgroup-specific entries and in a future repo-wide reframing of histopathology[] (the WNT and SHH subtype files carry the same "epidemiology as histopathology" pattern; flagged for follow-up).
  • Subgroup-specific driver mutations, prognosis stratification, and targeted therapy (SHH-pathway inhibitors, WNT radiation de-escalation, ONC201 for H3K27M-mutant variants) live in the existing subtype files.
  • Group 3 and Group 4 dismech entries are scoped as follow-up curation.
  • CSF biomarkers and leptomeningeal-dissemination staging biology are scoped as follow-up.