Pilocytic Astrocytoma

MONDO:0016691 Pathograph 10 Show in embeddings browser astrocytoma pediatric low-grade glioma

Pilocytic astrocytoma (PA) is a circumscribed World Health Organization grade 1 astrocytic glioma and the most common pediatric brain tumor. Most tumors arise in the cerebellum, optic pathway/hypothalamus, or brainstem and are driven by a single MAPK-pathway-activating alteration, most often KIAA1549-BRAF fusion. Clinical behavior is usually indolent, especially after gross total resection, but site-constrained tumors can cause major visual, endocrine, or hydrocephalic morbidity, and pilomyxoid astrocytoma represents a more aggressive histologic subtype within the same broader piloid disease program.

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2
Mappings
4
Pathophys.
3
Histopath.
3
Phenotypes
10
Pathograph
4
Genes
4
Medical Actions
3
Subtypes
5
Datasets
🔗

Mappings

MONDO
MONDO:0016691 pilocytic astrocytoma
skos:exactMatch MONDO
Primary MONDO disease anchor for the pilocytic astrocytoma mechanism graph.
NCIT
NCIT:C4047 Pilocytic Astrocytoma
skos:exactMatch NCIT
NCIT oncology disease mapping retained alongside MONDO per cancer curation guidance.
NCIT
NCIT:C4047 Pilocytic Astrocytoma
skos:exactMatch NCIT
NCIT oncology disease mapping retained alongside MONDO per cancer curation guidance.
◆

Subtypes

3
age group
Childhood Pilocytic Astrocytoma MONDO:0004000 NCIT:C4048
NCIT NCIT:C4048
Pediatric pilocytic astrocytoma usually presents in the first two decades of life and is enriched for posterior fossa location and BRAF rearrangements.
NCIT: Childhood Pilocytic Astrocytoma (skos:exactMatch) NCIT:C4048
Show evidence (1 reference)
PMID:36786200 SUPPORT Human Clinical
"Pilocytic astrocytoma (PA), a central nervous system (CNS) World Health Organization grade 1 tumor, is mainly seen in children or young adults aged 5-19."
Supports modeling PA as a predominantly childhood/young-adult disease and confirms WHO grade 1 status.
anatomic site
Cerebellar Pilocytic Astrocytoma MONDO:0003168 NCIT:C6809
NCIT NCIT:C6809
Posterior fossa PA is the most common anatomic presentation and is often amenable to gross total resection, but obstructive hydrocephalus and postoperative cerebellar morbidity remain important risks.
NCIT: Cerebellar Pilocytic Astrocytoma (skos:exactMatch) NCIT:C6809
Show evidence (1 reference)
PMID:16998597 SUPPORT Human Clinical
"demonstrated predilection for posterior fossa (61.7%)."
Supports cerebellar/posterior fossa PA as the most common anatomic presentation.
histology
Pilomyxoid Astrocytoma MONDO:0016692 NCIT:C40315
NCIT NCIT:C40315
Histologically pilomyxoid tumors usually arise in the hypothalamic/chiasmatic region, occur in younger children, and have shorter progression-free and overall survival than classic PA.
NCIT: Pilomyxoid Astrocytoma (skos:exactMatch) NCIT:C40315
Show evidence (1 reference)
PMID:14683543 SUPPORT Human Clinical
"Hypothalamic/chiasmatic PMAs occurred in a significantly younger population and were associated with substantially shorter PFS and OS times than were typical PAs."
Supports keeping pilomyxoid astrocytoma as a more aggressive histology-axis subtype within the broader pilocytic astrocytoma curation unit.
⚙

Pathophysiology

4
BRAF Fusion Oncogene Formation
Most pilocytic astrocytomas are initiated by tandem-duplication-mediated KIAA1549-BRAF fusion or related RAF fusions that remove BRAF autoinhibition and create constitutive upstream MAPK signaling.
neural stem cell CL:0000047 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves neural stem cell (CL:0000047). CL:0000047 is a cell type from the Cell Ontology.
KIAA1549 hgnc:22219 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves KIAA1549 (hgnc:22219). hgnc:22219 is a gene from the HUGO Gene Nomenclature Committee. BRAF hgnc:1097 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves BRAF (hgnc:1097). hgnc:1097 is a gene from the HUGO Gene Nomenclature Committee.
brain UBERON:0000955 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in brain (UBERON:0000955). UBERON:0000955 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Constitutive MAPK Cascade Activation RAF fusion signaling converges on sustained MAPK pathway output
Show evidence (1 reference)
PMID:28448514 SUPPORT Human Clinical
"A recurrent feature of PA is deregulation of the mitogen activated protein kinase (MAPK) pathway most often through KIAA1549-BRAF fusion, but also by other BRAF- or RAF1-gene fusions and point mutations (e.g. BRAFV600E)."
Human tumor profiling supports BRAF fusion formation as the dominant upstream initiating event in PA.
Constitutive MAPK Cascade Activation
Diverse driver lesions including KIAA1549-BRAF fusion, other RAF fusions, BRAFV600E mutation, and NF1 loss converge on persistent MAPK cascade activation, which is the shared core signaling dependency across PA subtypes.
BRAF hgnc:1097 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves BRAF (hgnc:1097). hgnc:1097 is a gene from the HUGO Gene Nomenclature Committee. RAF1 hgnc:9829 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves RAF1 (hgnc:9829). hgnc:9829 is a gene from the HUGO Gene Nomenclature Committee. NF1 hgnc:7765 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves NF1 (hgnc:7765). hgnc:7765 is a gene from the HUGO Gene Nomenclature Committee.
MAPK cascade GO:0000165 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased MAPK cascade (GO:0000165). GO:0000165 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Oncogene-Induced Senescence Sustained MAPK signaling can trigger a senescence brake in piloid tumors
Show evidence (2 references)
PMID:28448514 SUPPORT Human Clinical
"A recurrent feature of PA is deregulation of the mitogen activated protein kinase (MAPK) pathway most often through KIAA1549-BRAF fusion, but also by other BRAF- or RAF1-gene fusions and point mutations (e.g. BRAFV600E)."
Supports MAPK-pathway activation as the disease-level convergent signaling mechanism.
PMID:38837168 SUPPORT Other
"the loss of the NF1 gene activates 3 distinct Ras effector pathways, including the PI3K/AKT/mTOR pathway, the MEK/ERK pathway, and the cAMP pathway, which mediate glioma tumorigenesis"
Supports NF1 loss as an alternative upstream lesion converging on MAPK-pathway activation in gliomagenesis relevant to NF1-associated PA.
Oncogene-Induced Senescence
Activated BRAF in neural stem and progenitor cells induces a senescence program that limits proliferation and helps explain the usual WHO grade 1, indolent biology of pilocytic astrocytoma.
neural stem cell CL:0000047 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves neural stem cell (CL:0000047). CL:0000047 is a cell type from the Cell Ontology.
BRAF hgnc:1097 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves BRAF (hgnc:1097). hgnc:1097 is a gene from the HUGO Gene Nomenclature Committee.
cellular senescence GO:0090398 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased cellular senescence (GO:0090398). GO:0090398 is a biological process from the Gene Ontology. ↑ INCREASED negative regulation of cell population proliferation GO:0008285 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased negative regulation of cell population proliferation (GO:0008285). GO:0008285 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Senescence-Constrained Low-Grade Progression Barrier The BRAF-induced senescence program limits proliferation and helps maintain the usual low-grade, indolent tumor state.
Show evidence (2 references)
PMID:21636552 SUPPORT In Vitro
"BRAF(V600E)-expressing cells subsequently stopped proliferating and induced markers of oncogene-induced senescence including acidic β-galactosidase, PAI-1, and p16(INK4a) whereas controls did not."
Functional experiments show that activated BRAF can trigger a senescence brake after initial transformation in neural progenitor contexts relevant to PA.
PMID:21636552 SUPPORT In Vitro
"Induction of senescence by BRAF may help explain the low-grade pathobiology of pilocytic astrocytoma"
Directly supports senescence as a mechanistic explanation for the usual indolent, grade 1 biology of PA.
Senescence-Constrained Low-Grade Progression Barrier
Oncogene-induced senescence constrains proliferation after BRAF-driven partial transformation and helps account for the usual WHO grade 1, indolent state. This is modeled as a barrier to malignant progression, not as a claim that progression is impossible.
Show evidence (2 references)
PMID:21636552 SUPPORT In Vitro
"Induction of senescence by BRAF may help explain the low-grade pathobiology of pilocytic astrocytoma"
The experimental conclusion supports oncogene-induced senescence as a mechanism constraining pilocytic astrocytoma to its usual low-grade state.
PMID:21636552 SUPPORT Human Clinical
"Immunohistochemical examination of 66 pilocytic astrocytomas revealed p16(INK4a) immunoreactivity in the majority of cases, but patients with tumors negative for p16(INK4a) had significantly shorter overall survival."
The human tumor series associates absence of the p16 senescence marker with worse outcome, providing clinical corroboration without proving that the senescence barrier alone determines progression.
✶

Histopathology

3
Biphasic Pattern VERY_FREQUENT
Classic PA shows a biphasic architecture with compact piloid areas and looser microcystic zones.
Show evidence (1 reference)
PMID:16998597 SUPPORT Human Clinical
"On histopathology, biphasic pattern (89.2%) along with Rosenthal fibers (66.7%) and eosinophilic granular bodies (60%) were present in the majority of cases."
Supports biphasic architecture as a very frequent histopathologic feature of PA.
Rosenthal Fibers FREQUENT
Dense eosinophilic Rosenthal fibers are a characteristic piloid histologic feature, though not present in every case.
Show evidence (1 reference)
PMID:16998597 SUPPORT Human Clinical
"On histopathology, biphasic pattern (89.2%) along with Rosenthal fibers (66.7%) and eosinophilic granular bodies (60%) were present in the majority of cases."
Supports Rosenthal fibers as a frequent microscopic finding in PA.
Eosinophilic Granular Bodies FREQUENT
Eosinophilic granular bodies are common but non-universal microscopic inclusions in classic PA.
Show evidence (1 reference)
PMID:16998597 SUPPORT Human Clinical
"On histopathology, biphasic pattern (89.2%) along with Rosenthal fibers (66.7%) and eosinophilic granular bodies (60%) were present in the majority of cases."
Supports eosinophilic granular bodies as a frequent microscopic feature of PA.
⬡

Pathograph

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

Phenotypes

3
Eye 1
Visual Impairment FREQUENT HP:0000505 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Visual impairment (HP:0000505). HP:0000505 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38837168 SUPPORT Other
"OPGs in individuals with NF1 primarily affect the optic pathway and lead to visual disturbance."
Supports visual impairment as a clinically important phenotype in the optic pathway subset of PA, especially in NF1-associated disease.
Nervous System 1
Hydrocephalus FREQUENT HP:0000238 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hydrocephalus (HP:0000238). HP:0000238 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37021292 SUPPORT Human Clinical
"79 patients had hydrocephalus at diagnosis and 48% required preoperative treatment."
Supports hydrocephalus as a frequent presenting phenotype in cerebellar PA.
Other 1
Hypopituitarism HP:0040075 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hypopituitarism (HP:0040075). HP:0040075 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37033188 SUPPORT Other
"The main risks are to threaten vision loss by progressive tumor damage to optic pathways; furthermore, invasion of the hypothalamus can lead to diencephalic syndrome in infancy and hypopituitarism later in life."
Supports hypopituitarism as an important site-dependent phenotype of hypothalamic/optic pathway PA.
🧬

Genetic Associations

4
BRAF (Somatic activating fusion or mutation)
Gene: BRAF hgnc:1097 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is BRAF (hgnc:1097). hgnc:1097 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: SOMATIC_DRIVER variant_origin: SOMATIC
Show evidence (1 reference)
PMID:28448514 SUPPORT Human Clinical
"A recurrent feature of PA is deregulation of the mitogen activated protein kinase (MAPK) pathway most often through KIAA1549-BRAF fusion, but also by other BRAF- or RAF1-gene fusions and point mutations (e.g. BRAFV600E)."
Supports BRAF as the dominant somatic driver locus in PA through fusion and point-mutation mechanisms.
KIAA1549 (Somatic fusion partner)
Gene: KIAA1549 hgnc:22219 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is KIAA1549 (hgnc:22219). hgnc:22219 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: COOPERATING variant_origin: SOMATIC
Show evidence (1 reference)
PMID:28448514 SUPPORT Human Clinical
"A recurrent feature of PA is deregulation of the mitogen activated protein kinase (MAPK) pathway most often through KIAA1549-BRAF fusion, but also by other BRAF- or RAF1-gene fusions and point mutations (e.g. BRAFV600E)."
Supports KIAA1549 as the canonical recurrent BRAF fusion partner in PA.
NF1 (Germline tumor predisposition with biallelic tumor inactivation context)
Gene: NF1 hgnc:7765 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is NF1 (hgnc:7765). hgnc:7765 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: RISK_FACTOR variant_origin: GERMLINE_AND_SOMATIC
Show evidence (1 reference)
PMID:35945463 SUPPORT Human Clinical
"The first harbored biallelic NF1 inactivation only, occurred primarily during childhood, followed a more indolent clinical course, and had a unique epigenetic signature for which we propose the terminology "pilocytic astrocytoma, arising in the setting of NF1"."
Supports NF1-associated PA as a predisposition-context subset with biallelic NF1 inactivation converging on the same piloid disease program.
RAF1 (Somatic fusion driver)
Gene: RAF1 hgnc:9829 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is RAF1 (hgnc:9829). hgnc:9829 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: SOMATIC_DRIVER variant_origin: SOMATIC
Show evidence (1 reference)
PMID:28448514 SUPPORT Human Clinical
"A recurrent feature of PA is deregulation of the mitogen activated protein kinase (MAPK) pathway most often through KIAA1549-BRAF fusion, but also by other BRAF- or RAF1-gene fusions and point mutations (e.g. BRAFV600E)."
Supports RAF1 as an uncommon alternative fusion-driver locus contributing to MAPK-pathway activation in PA.
💊

Medical Actions

4
Gross Total Resection
Action: gross total resectionNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is gross total resection (NCIT:C131672). NCIT:C131672 is a clinical intervention from the NCI Thesaurus. Ontology label: Gross Total Resection NCIT:C131672
Gross total resection is preferred for surgically accessible tumors and remains the core first-line treatment for most cerebellar PA.
Show evidence (2 references)
PMID:26351221 SUPPORT Other
"Surgical resection remains the first-line treatment with complete removal of the tumor the goal."
Supports surgical resection, ideally gross total removal, as first-line therapy for accessible PA.
PMID:37021292 SUPPORT Human Clinical
"Early treatment with the intention of GTR should be considered, opting, if this is not possible, to leave a tumor residue over neurological damage."
Human cohort evidence supports gross total resection as the surgical goal while preserving neurologic function.
Carboplatin/Vincristine 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. Ontology label: Chemotherapy NCIT:C15632
Agent: carboplatin CHEBI:31355 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses carboplatin (CHEBI:31355). CHEBI:31355 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.
Carboplatin/vincristine remains a standard conventional regimen for residual, progressive, or unresectable pediatric low-grade glioma when surgery alone is insufficient and radiotherapy is undesirable.
Show evidence (1 reference)
PMID:22665535 SUPPORT Human Clinical
"Previously untreated children younger than age 10 years with progressive or residual LGGs were eligible. Children were randomly assigned to receive carboplatin and vincristine (CV) or thioguanine, procarbazine, lomustine, and vincristine (TPCV)."
Supports carboplatin/vincristine as an established pediatric low-grade glioma regimen used when complete resection is not feasible.
Selumetinib
Action: targeted therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is targeted therapy (NCIT:C93352). NCIT:C93352 is a clinical intervention from the NCI Thesaurus. Ontology label: Targeted Therapy NCIT:C93352
Agent: selumetinib NCIT:C66939 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses selumetinib (NCIT:C66939). NCIT:C66939 is a therapeutic agent from the NCI Thesaurus.
MEK inhibition with selumetinib is active in recurrent or progressive MAPK-driven low-grade glioma, including pilocytic astrocytoma and optic-pathway/hypothalamic subsets where visual preservation matters.
Mechanism Target:
INHIBITS Constitutive MAPK Cascade Activation — MEK inhibition suppresses the shared MAPK signaling dependency of PA.
Show evidence (2 references)
PMID:40241281 SUPPORT Human Clinical
"Selumetinib provided stability and responses across many pLGG subgroups, and some patients achieved prolonged disease control without additional therapy."
Supports selumetinib as an active targeted therapy across recurrent/progressive pediatric low-grade glioma subgroups that include PA.
PMID:33631016 SUPPORT Human Clinical
"Selumetinib was tolerable and led to responses and prolonged disease stability in children with recurrent/progressive OPHGs based upon radiographic response, PFS, and visual outcomes."
Supports selumetinib specifically in the optic pathway/hypothalamic subset where functional visual outcomes are central.
Tovorafenib
Action: targeted therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is targeted therapy (NCIT:C93352). NCIT:C93352 is a clinical intervention from the NCI Thesaurus. Ontology label: Targeted Therapy NCIT:C93352
Agent: tovorafenib NCIT:C106254 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses tovorafenib (NCIT:C106254). NCIT:C106254 is a therapeutic agent from the NCI Thesaurus.
Tovorafenib is an FDA-approved type II RAF inhibitor for relapsed or refractory pediatric low-grade glioma with BRAF fusion, rearrangement, or V600E mutation, making it directly relevant to recurrent BRAF-altered PA.
Mechanism Target:
INHIBITS Constitutive MAPK Cascade Activation — Type II RAF inhibition targets the upstream RAF/MAPK dependency in BRAF-altered PA.
Show evidence (2 references)
NCIT:C106254 SUPPORT Other
"Tovorafenib | Accepted_Therapeutic_Use_For | - | - | for patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation."
NCI Thesaurus asserts accepted therapeutic use of tovorafenib for relapsed or refractory pediatric low-grade glioma with BRAF alteration; pilocytic astrocytoma is the prototypical BRAF-fusion pediatric low-grade glioma.
PMID:39412085 SUPPORT Other
"On 23 April 2024, the U.S. FDA approved a new type II RAF inhibitor, tovorafenib (OJEMDATM), previously known as DAY101, for the treatment of patients aged 6 months and older with relapsed or refractory (R/R) pLGG harboring a BRAF fusion or rearrangement, or BRAF V600E mutation."
Review-level evidence supports current clinical use of tovorafenib in recurrent BRAF-altered pediatric low-grade glioma, a setting directly relevant to many recurrent PA cases.
📊

Related Datasets

5
RNA-sequencing of six Pilocytic astrocytoma tumors ega:EGAS00001002149
Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. A recurrent feature of PA is deregulation of the mitogen activated protein kinase (MAPK) pathway most often through KIAA1549-BRAF fusion, but also by other BRAF- or RAF1-gene fusions and point mutations (e.g. BRAFV600E). These features may serve as diagnostic and prognostic markers, and also facilitate development of targeted therapy. The aim of this study was to characterize the genetic alterations underlying the development of PA tumor in six cases, and evaluate methods for fusion oncogene detection.
human
PMID:28448514
European Genome-phenome Archive study, matched because the disease is named in the study's own title ("Pilocytic Astrocytoma"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.
Detection and genomic analysis of BRAF fusions in Juvenile Pilocytic Astrocytoma through the combination and integration of multi-omic data ega:EGAS00001006388
Juvenile Pilocytic Astrocytoma (JPAs) are highly vascular tumors and show pervasive immune infiltration, which can lead to low tumor cell purity in clinical samples. In some instances, this results in gene fusions that are difficult to detect with conventional omics approaches including RNA-Seq. To this effect, we applied RNA-Seq as well as linked-read whole-genome sequencing and in situ Hi-C as new approaches to detect and characterize low-frequency gene fusions at the genomic, transcriptomic and spatial level. Overall, we demonstrate the power of integrating multi-omic datasets to identify low frequency fusions and characterize the JPA genome at high resolution.
human
European Genome-phenome Archive study, matched because the disease is named in the study's own title ("Pilocytic Astrocytoma"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.
Proteogenomics reveals two distinct biological pilocytic astrocytoma subgroups ega:EGAS00001006402
Pilocytic astrocytoma (PA) is the most common pediatric brain tumor and driven by aberrant MAPK signaling, typically mediated by BRAF alterations. While five-year overall survival rates exceed 95%, tumor recurrence constitutes a major clinical challenge in incompletely resected tumors despite chemotherapeutic or radiation based therapies. Therefore, we used proteogenomics to discern the biological heterogeneity of PA to improve classification of this tumor entity and identify novel therapeutic targets. Our proteogenomics approach integrates RNA sequencing and LC/MS-based proteomic profiling data from a cohort of 58 confirmed, primary PA samples.
human
European Genome-phenome Archive study, matched because the disease is named in the study's own title ("Pilocytic Astrocytoma"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.
Human Pilocytic Astrocytoma Single Cell RNA Sequencing dbgap:phs001854
Pilocytic astrocytoma (PA), the most common childhood brain tumor, is a low-grade glioma with a single driver BRAF rearrangement. Here, we perform scRNAseq in six PAs using methods that enabled detection of the rearrangement. When compared to higher-grade gliomas, a strikingly higher proportion of the PA cancer cells exhibit a differentiated, astrocyte-like phenotype. A smaller proportion of cells exhibit a progenitor-like phenotype with evidence of proliferation. These express a mitogen-activated protein kinase (MAPK) program that was absent from higher-grade gliomas.
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 ("Pilocytic Astrocytoma"). Retrieved 2026-08-02.
Pilocytic Astrocytoma in NF1 dbgap:phs000563
Neurofibromatosis type 1 (NF1) inherited cancer predisposition syndrome is one of the most common autosomal dominant tumor predisposition syndromes in which affected individuals develop brain tumors. These low-grade glial neoplasms (pilocytic astrocytomas) typically arise in children younger than 7 years of age and are hypothesized to result from a combination of germline and acquired somatic NF1 tumor suppressor gene mutations.
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 ("Pilocytic Astrocytoma"). Retrieved 2026-08-02.
{ }

Source YAML

click to show 
name: Pilocytic Astrocytoma
creation_date: "2026-04-12T00:00:00Z"
description: >-
  Pilocytic astrocytoma (PA) is a circumscribed World Health Organization grade 1
  astrocytic glioma and the most common pediatric brain tumor. Most tumors arise
  in the cerebellum, optic pathway/hypothalamus, or brainstem and are driven by a
  single MAPK-pathway-activating alteration, most often KIAA1549-BRAF fusion.
  Clinical behavior is usually indolent, especially after gross total resection,
  but site-constrained tumors can cause major visual, endocrine, or hydrocephalic
  morbidity, and pilomyxoid astrocytoma represents a more aggressive histologic
  subtype within the same broader piloid disease program.
categories:
- Central Nervous System Neoplasm
- Pediatric Brain Tumor
- Circumscribed Astrocytic Glioma
- MAPK-Driven Tumor
parents:
- astrocytoma
- pediatric low-grade glioma
disease_term:
  preferred_term: pilocytic astrocytoma
  term:
    id: MONDO:0016691
    label: pilocytic astrocytoma
has_subtypes:
- name: Childhood
  display_name: Childhood Pilocytic Astrocytoma
  classification: age_group
  subtype_term:
    preferred_term: childhood pilocytic astrocytoma
    term:
      id: MONDO:0004000
      label: childhood pilocytic astrocytoma
  mappings:
    mondo_mappings:
    - term:
        id: MONDO:0004000
        label: childhood pilocytic astrocytoma
      mapping_predicate: skos:exactMatch
      mapping_source: MONDO
      mapping_justification: MONDO age-qualified subclass for childhood PA.
    ncit_mappings:
    - term:
        id: NCIT:C4048
        label: Childhood Pilocytic Astrocytoma
      mapping_predicate: skos:exactMatch
      mapping_source: NCIT
      mapping_justification: NCIT pediatric oncology subclass for childhood PA.
  description: >-
    Pediatric pilocytic astrocytoma usually presents in the first two decades of
    life and is enriched for posterior fossa location and BRAF rearrangements.
  evidence:
  - reference: PMID:36786200
    reference_title: "Pilocytic astrocytoma harboring a novel GNAI3-BRAF fusion."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Pilocytic astrocytoma (PA), a central nervous system (CNS) World Health
      Organization grade 1 tumor, is mainly seen in children or young adults aged 5-19.
    explanation: >-
      Supports modeling PA as a predominantly childhood/young-adult disease and
      confirms WHO grade 1 status.
- name: Cerebellar
  display_name: Cerebellar Pilocytic Astrocytoma
  classification: anatomic_site
  subtype_term:
    preferred_term: cerebellar pilocytic astrocytoma
    term:
      id: MONDO:0003168
      label: cerebellar pilocytic astrocytoma
  mappings:
    mondo_mappings:
    - term:
        id: MONDO:0003168
        label: cerebellar pilocytic astrocytoma
      mapping_predicate: skos:exactMatch
      mapping_source: MONDO
      mapping_justification: MONDO site-qualified subclass for cerebellar PA.
    ncit_mappings:
    - term:
        id: NCIT:C6809
        label: Cerebellar Pilocytic Astrocytoma
      mapping_predicate: skos:exactMatch
      mapping_source: NCIT
      mapping_justification: NCIT pediatric neuro-oncology site-qualified subclass.
  description: >-
    Posterior fossa PA is the most common anatomic presentation and is often
    amenable to gross total resection, but obstructive hydrocephalus and
    postoperative cerebellar morbidity remain important risks.
  evidence:
  - reference: PMID:16998597
    reference_title: "Neuropathological spectrum of pilocytic astrocytoma: an Indian series of 120 cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      demonstrated predilection for posterior fossa (61.7%).
    explanation: >-
      Supports cerebellar/posterior fossa PA as the most common anatomic
      presentation.
- name: Pilomyxoid
  display_name: Pilomyxoid Astrocytoma
  classification: histology
  subtype_term:
    preferred_term: pilomyxoid astrocytoma
    term:
      id: MONDO:0016692
      label: pilomyxoid astrocytoma
  mappings:
    mondo_mappings:
    - term:
        id: MONDO:0016692
        label: pilomyxoid astrocytoma
      mapping_predicate: skos:exactMatch
      mapping_source: MONDO
      mapping_justification: MONDO histologic subtype term used here as subtype grounding.
    ncit_mappings:
    - term:
        id: NCIT:C40315
        label: Pilomyxoid Astrocytoma
      mapping_predicate: skos:exactMatch
      mapping_source: NCIT
      mapping_justification: NCIT histologic subtype term used as flat histology-axis grounding.
  description: >-
    Histologically pilomyxoid tumors usually arise in the hypothalamic/chiasmatic
    region, occur in younger children, and have shorter progression-free and
    overall survival than classic PA.
  evidence:
  - reference: PMID:14683543
    reference_title: "Pilocytic and pilomyxoid hypothalamic/chiasmatic astrocytomas."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Hypothalamic/chiasmatic PMAs occurred in a significantly younger population
      and were associated with substantially shorter PFS and OS times than were
      typical PAs.
    explanation: >-
      Supports keeping pilomyxoid astrocytoma as a more aggressive histology-axis
      subtype within the broader pilocytic astrocytoma curation unit.
pathophysiology:
- name: BRAF Fusion Oncogene Formation
  description: >-
    Most pilocytic astrocytomas are initiated by tandem-duplication-mediated
    KIAA1549-BRAF fusion or related RAF fusions that remove BRAF autoinhibition
    and create constitutive upstream MAPK signaling.
  genes:
  - preferred_term: KIAA1549
    term:
      id: hgnc:22219
      label: KIAA1549
  - preferred_term: BRAF
    term:
      id: hgnc:1097
      label: BRAF
  cell_types:
  - preferred_term: neural stem cell
    term:
      id: CL:0000047
      label: neural stem cell
  locations:
  - preferred_term: brain
    term:
      id: UBERON:0000955
      label: brain
  evidence:
  - reference: PMID:28448514
    reference_title: "A new GTF2I-BRAF fusion mediating MAPK pathway activation in pilocytic astrocytoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A recurrent feature of PA is deregulation of the mitogen activated protein
      kinase (MAPK) pathway most often through KIAA1549-BRAF fusion, but also by
      other BRAF- or RAF1-gene fusions and point mutations (e.g. BRAFV600E).
    explanation: >-
      Human tumor profiling supports BRAF fusion formation as the dominant upstream
      initiating event in PA.
  downstream:
  - target: Constitutive MAPK Cascade Activation
    description: RAF fusion signaling converges on sustained MAPK pathway output
- name: Constitutive MAPK Cascade Activation
  description: >-
    Diverse driver lesions including KIAA1549-BRAF fusion, other RAF fusions,
    BRAFV600E mutation, and NF1 loss converge on persistent MAPK cascade
    activation, which is the shared core signaling dependency across PA subtypes.
  genes:
  - preferred_term: BRAF
    term:
      id: hgnc:1097
      label: BRAF
  - preferred_term: RAF1
    term:
      id: hgnc:9829
      label: RAF1
  - preferred_term: NF1
    term:
      id: hgnc:7765
      label: NF1
  biological_processes:
  - preferred_term: MAPK cascade
    modifier: INCREASED
    term:
      id: GO:0000165
      label: MAPK cascade
  evidence:
  - reference: PMID:28448514
    reference_title: "A new GTF2I-BRAF fusion mediating MAPK pathway activation in pilocytic astrocytoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A recurrent feature of PA is deregulation of the mitogen activated protein
      kinase (MAPK) pathway most often through KIAA1549-BRAF fusion, but also by
      other BRAF- or RAF1-gene fusions and point mutations (e.g. BRAFV600E).
    explanation: >-
      Supports MAPK-pathway activation as the disease-level convergent signaling mechanism.
  - reference: PMID:38837168
    reference_title: "An Overview of Optic Pathway Glioma With Neurofibromatosis Type 1: Pathogenesis, Risk Factors, and Therapeutic Strategies."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      the loss of the NF1 gene activates 3 distinct Ras effector pathways,
      including the PI3K/AKT/mTOR pathway, the MEK/ERK pathway, and the cAMP
      pathway, which mediate glioma tumorigenesis
    explanation: >-
      Supports NF1 loss as an alternative upstream lesion converging on MAPK-pathway
      activation in gliomagenesis relevant to NF1-associated PA.
  downstream:
  - target: Oncogene-Induced Senescence
    description: Sustained MAPK signaling can trigger a senescence brake in piloid tumors
    evidence:
    - reference: PMID:21636552
      reference_title: "BRAF activation induces transformation and then senescence in human neural stem cells: a pilocytic astrocytoma model."
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        BRAF(V600E)-expressing cells subsequently stopped proliferating and induced
        markers of oncogene-induced senescence including acidic β-galactosidase,
        PAI-1, and p16(INK4a) whereas controls did not.
      explanation: >-
        The BRAF V600E experiment supports this edge for that driver branch; it
        does not show that every RAF fusion or NF1-associated PA engages the same
        senescence brake.
- name: Oncogene-Induced Senescence
  conforms_to: "senescence_tumor_suppression#Senescence-Associated Tumor-Suppressive Arrest"
  role: central_effector
  biological_scale: CELLULAR
  description: >-
    Activated BRAF in neural stem and progenitor cells induces a senescence
    program that limits proliferation and helps explain the usual WHO grade 1,
    indolent biology of pilocytic astrocytoma.
  genes:
  - preferred_term: BRAF
    term:
      id: hgnc:1097
      label: BRAF
  cell_types:
  - preferred_term: neural stem cell
    term:
      id: CL:0000047
      label: neural stem cell
  biological_processes:
  - preferred_term: cellular senescence
    modifier: INCREASED
    term:
      id: GO:0090398
      label: cellular senescence
  - preferred_term: negative regulation of cell population proliferation
    modifier: INCREASED
    term:
      id: GO:0008285
      label: negative regulation of cell population proliferation
  evidence:
  - reference: PMID:21636552
    reference_title: "BRAF activation induces transformation and then senescence in human neural stem cells: a pilocytic astrocytoma model."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      BRAF(V600E)-expressing cells subsequently stopped proliferating and induced
      markers of oncogene-induced senescence including acidic β-galactosidase,
      PAI-1, and p16(INK4a) whereas controls did not.
    explanation: >-
      Functional experiments show that activated BRAF can trigger a senescence
      brake after initial transformation in neural progenitor contexts relevant to PA.
  - reference: PMID:21636552
    reference_title: "BRAF activation induces transformation and then senescence in human neural stem cells: a pilocytic astrocytoma model."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Induction of senescence by BRAF may help explain the low-grade pathobiology
      of pilocytic astrocytoma
    explanation: >-
      Directly supports senescence as a mechanistic explanation for the usual
      indolent, grade 1 biology of PA.
  downstream:
  - target: Senescence-Constrained Low-Grade Progression Barrier
    description: >-
      The BRAF-induced senescence program limits proliferation and helps maintain
      the usual low-grade, indolent tumor state.
    evidence:
    - reference: PMID:21636552
      reference_title: "BRAF activation induces transformation and then senescence in human neural stem cells: a pilocytic astrocytoma model."
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        Induction of senescence by BRAF may help explain the low-grade pathobiology
        of pilocytic astrocytoma
      explanation: >-
        The experimental conclusion directly links BRAF-induced senescence to the
        low-grade biology represented by the downstream barrier node.
- name: Senescence-Constrained Low-Grade Progression Barrier
  conforms_to: "senescence_tumor_suppression#Barrier to Malignant Transformation"
  role: consequence
  biological_scale: TISSUE
  description: >-
    Oncogene-induced senescence constrains proliferation after BRAF-driven partial
    transformation and helps account for the usual WHO grade 1, indolent state.
    This is modeled as a barrier to malignant progression, not as a claim that
    progression is impossible.
  evidence:
  - reference: PMID:21636552
    reference_title: "BRAF activation induces transformation and then senescence in human neural stem cells: a pilocytic astrocytoma model."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Induction of senescence by BRAF may help explain the low-grade pathobiology
      of pilocytic astrocytoma
    explanation: >-
      The experimental conclusion supports oncogene-induced senescence as a
      mechanism constraining pilocytic astrocytoma to its usual low-grade state.
  - reference: PMID:21636552
    reference_title: "BRAF activation induces transformation and then senescence in human neural stem cells: a pilocytic astrocytoma model."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Immunohistochemical examination of 66 pilocytic astrocytomas revealed
      p16(INK4a) immunoreactivity in the majority of cases, but patients with
      tumors negative for p16(INK4a) had significantly shorter overall survival.
    explanation: >-
      The human tumor series associates absence of the p16 senescence marker with
      worse outcome, providing clinical corroboration without proving that the
      senescence barrier alone determines progression.
phenotypes:
- category: Neurological
  name: Hydrocephalus
  subtype: Cerebellar
  frequency: FREQUENT
  description: >-
    Obstructive hydrocephalus is a common presenting feature of cerebellar PA and
    often requires individualized preoperative management.
  phenotype_term:
    preferred_term: Hydrocephalus
    term:
      id: HP:0000238
      label: Hydrocephalus
  evidence:
  - reference: PMID:37021292
    reference_title: "Cerebellar pilocytic astrocytoma. Retrospective cohort study assessing postoperative functional outcome, cerebellar mutism and hydrocephalus."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      79 patients had hydrocephalus at diagnosis and 48% required preoperative treatment.
    explanation: >-
      Supports hydrocephalus as a frequent presenting phenotype in cerebellar PA.
- category: Ophthalmologic
  name: Visual Impairment
  frequency: FREQUENT
  description: >-
    Visual dysfunction is a major morbidity of optic pathway/hypothalamic PA,
    especially in NF1-associated tumors affecting the anterior visual pathways.
  phenotype_term:
    preferred_term: Visual impairment
    term:
      id: HP:0000505
      label: Visual impairment
  evidence:
  - reference: PMID:38837168
    reference_title: "An Overview of Optic Pathway Glioma With Neurofibromatosis Type 1: Pathogenesis, Risk Factors, and Therapeutic Strategies."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      OPGs in individuals with NF1 primarily affect the optic pathway and lead to
      visual disturbance.
    explanation: >-
      Supports visual impairment as a clinically important phenotype in the optic
      pathway subset of PA, especially in NF1-associated disease.
- category: Endocrine
  name: Hypopituitarism
  description: >-
    Hypothalamic invasion by optic pathway/hypothalamic PA can cause later
    hypopituitarism after early-life tumor growth or treatment.
  phenotype_term:
    preferred_term: Hypopituitarism
    term:
      id: HP:0040075
      label: Hypopituitarism
  evidence:
  - reference: PMID:37033188
    reference_title: "A new era for optic pathway glioma: A developmental brain tumor with life-long health consequences."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The main risks are to threaten vision loss by progressive tumor damage to
      optic pathways; furthermore, invasion of the hypothalamus can lead to
      diencephalic syndrome in infancy and hypopituitarism later in life.
    explanation: >-
      Supports hypopituitarism as an important site-dependent phenotype of
      hypothalamic/optic pathway PA.
histopathology:
- name: Biphasic Pattern
  finding_term:
    preferred_term: biphasic pattern
    term:
      id: NCIT:C35907
      label: Biphasic Pattern
  frequency: VERY_FREQUENT
  description: >-
    Classic PA shows a biphasic architecture with compact piloid areas and looser
    microcystic zones.
  evidence:
  - reference: PMID:16998597
    reference_title: "Neuropathological spectrum of pilocytic astrocytoma: an Indian series of 120 cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      On histopathology, biphasic pattern (89.2%) along with Rosenthal fibers
      (66.7%) and eosinophilic granular bodies (60%) were present in the majority
      of cases.
    explanation: >-
      Supports biphasic architecture as a very frequent histopathologic feature of PA.
- name: Rosenthal Fibers
  finding_term:
    preferred_term: Rosenthal fibers
    term:
      id: NCIT:C41465
      label: Rosenthal Fibers Present
  frequency: FREQUENT
  description: >-
    Dense eosinophilic Rosenthal fibers are a characteristic piloid histologic
    feature, though not present in every case.
  evidence:
  - reference: PMID:16998597
    reference_title: "Neuropathological spectrum of pilocytic astrocytoma: an Indian series of 120 cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      On histopathology, biphasic pattern (89.2%) along with Rosenthal fibers
      (66.7%) and eosinophilic granular bodies (60%) were present in the majority
      of cases.
    explanation: >-
      Supports Rosenthal fibers as a frequent microscopic finding in PA.
- name: Eosinophilic Granular Bodies
  finding_term:
    preferred_term: eosinophilic granular bodies
    term:
      id: NCIT:C41463
      label: Eosinophilic Granular Bodies Present
  frequency: FREQUENT
  description: >-
    Eosinophilic granular bodies are common but non-universal microscopic
    inclusions in classic PA.
  evidence:
  - reference: PMID:16998597
    reference_title: "Neuropathological spectrum of pilocytic astrocytoma: an Indian series of 120 cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      On histopathology, biphasic pattern (89.2%) along with Rosenthal fibers
      (66.7%) and eosinophilic granular bodies (60%) were present in the majority
      of cases.
    explanation: >-
      Supports eosinophilic granular bodies as a frequent microscopic feature of PA.
genetic:
- name: BRAF
  gene_term:
    preferred_term: BRAF
    term:
      id: hgnc:1097
      label: BRAF
  association: Somatic activating fusion or mutation
  relationship_type: SOMATIC_DRIVER
  variant_origin: SOMATIC
  evidence:
  - reference: PMID:28448514
    reference_title: "A new GTF2I-BRAF fusion mediating MAPK pathway activation in pilocytic astrocytoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A recurrent feature of PA is deregulation of the mitogen activated protein
      kinase (MAPK) pathway most often through KIAA1549-BRAF fusion, but also by
      other BRAF- or RAF1-gene fusions and point mutations (e.g. BRAFV600E).
    explanation: >-
      Supports BRAF as the dominant somatic driver locus in PA through fusion and
      point-mutation mechanisms.
  notes: >-
    KIAA1549-BRAF fusion is the dominant alteration in childhood and cerebellar PA,
    while BRAFV600E is a less common alternative driver.
- name: KIAA1549
  gene_term:
    preferred_term: KIAA1549
    term:
      id: hgnc:22219
      label: KIAA1549
  association: Somatic fusion partner
  relationship_type: COOPERATING
  variant_origin: SOMATIC
  evidence:
  - reference: PMID:28448514
    reference_title: "A new GTF2I-BRAF fusion mediating MAPK pathway activation in pilocytic astrocytoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A recurrent feature of PA is deregulation of the mitogen activated protein
      kinase (MAPK) pathway most often through KIAA1549-BRAF fusion, but also by
      other BRAF- or RAF1-gene fusions and point mutations (e.g. BRAFV600E).
    explanation: >-
      Supports KIAA1549 as the canonical recurrent BRAF fusion partner in PA.
  notes: >-
    KIAA1549-BRAF fusion is especially common in cerebellar and pediatric PA.
- name: NF1
  gene_term:
    preferred_term: NF1
    term:
      id: hgnc:7765
      label: NF1
  association: Germline tumor predisposition with biallelic tumor inactivation context
  relationship_type: RISK_FACTOR
  variant_origin: GERMLINE_AND_SOMATIC
  evidence:
  - reference: PMID:35945463
    reference_title: "Multiplatform molecular analyses refine classification of gliomas arising in patients with neurofibromatosis type 1."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The first harbored biallelic NF1 inactivation only, occurred primarily during
      childhood, followed a more indolent clinical course, and had a unique
      epigenetic signature for which we propose the terminology "pilocytic
      astrocytoma, arising in the setting of NF1".
    explanation: >-
      Supports NF1-associated PA as a predisposition-context subset with biallelic
      NF1 inactivation converging on the same piloid disease program.
  notes: >-
    NF1-associated optic pathway gliomas are usually pilocytic and often follow a
    childhood-onset, indolent course.
- name: RAF1
  gene_term:
    preferred_term: RAF1
    term:
      id: hgnc:9829
      label: RAF1
  association: Somatic fusion driver
  relationship_type: SOMATIC_DRIVER
  variant_origin: SOMATIC
  evidence:
  - reference: PMID:28448514
    reference_title: "A new GTF2I-BRAF fusion mediating MAPK pathway activation in pilocytic astrocytoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A recurrent feature of PA is deregulation of the mitogen activated protein
      kinase (MAPK) pathway most often through KIAA1549-BRAF fusion, but also by
      other BRAF- or RAF1-gene fusions and point mutations (e.g. BRAFV600E).
    explanation: >-
      Supports RAF1 as an uncommon alternative fusion-driver locus contributing to
      MAPK-pathway activation in PA.
  notes: >-
    RAF1 fusions are less common than BRAF alterations but fit the same MAPK-driven
    disease program.
treatments:
- name: Gross Total Resection
  description: >-
    Gross total resection is preferred for surgically accessible tumors and remains
    the core first-line treatment for most cerebellar PA.
  treatment_term:
    preferred_term: gross total resection
    term:
      id: NCIT:C131672
      label: Gross Total Resection
  evidence:
  - reference: PMID:26351221
    reference_title: "Pediatric cerebellar astrocytoma: a review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Surgical resection remains the first-line treatment with complete removal of
      the tumor the goal.
    explanation: >-
      Supports surgical resection, ideally gross total removal, as first-line
      therapy for accessible PA.
  - reference: PMID:37021292
    reference_title: "Cerebellar pilocytic astrocytoma. Retrospective cohort study assessing postoperative functional outcome, cerebellar mutism and hydrocephalus."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Early treatment with the intention of GTR should be considered, opting, if
      this is not possible, to leave a tumor residue over neurological damage.
    explanation: >-
      Human cohort evidence supports gross total resection as the surgical goal
      while preserving neurologic function.
- name: Carboplatin/Vincristine Chemotherapy
  description: >-
    Carboplatin/vincristine remains a standard conventional regimen for residual,
    progressive, or unresectable pediatric low-grade glioma when surgery alone is
    insufficient and radiotherapy is undesirable.
  treatment_term:
    preferred_term: chemotherapy
    term:
      id: NCIT:C15632
      label: Chemotherapy
    therapeutic_agent:
    - preferred_term: carboplatin
      term:
        id: CHEBI:31355
        label: carboplatin
    - preferred_term: vincristine
      term:
        id: CHEBI:28445
        label: vincristine
  evidence:
  - reference: PMID:22665535
    reference_title: "Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children: a report from the Children's Oncology Group."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Previously untreated children younger than age 10 years with progressive or
      residual LGGs were eligible. Children were randomly assigned to receive
      carboplatin and vincristine (CV) or thioguanine, procarbazine, lomustine,
      and vincristine (TPCV).
    explanation: >-
      Supports carboplatin/vincristine as an established pediatric low-grade glioma
      regimen used when complete resection is not feasible.
- name: Selumetinib
  description: >-
    MEK inhibition with selumetinib is active in recurrent or progressive
    MAPK-driven low-grade glioma, including pilocytic astrocytoma and
    optic-pathway/hypothalamic subsets where visual preservation matters.
  treatment_term:
    preferred_term: targeted therapy
    term:
      id: NCIT:C93352
      label: Targeted Therapy
    therapeutic_agent:
    - preferred_term: selumetinib
      term:
        id: NCIT:C66939
        label: Selumetinib
  target_mechanisms:
  - target: Constitutive MAPK Cascade Activation
    treatment_effect: INHIBITS
    description: MEK inhibition suppresses the shared MAPK signaling dependency of PA.
  evidence:
  - reference: PMID:40241281
    reference_title: "A phase 2 PBTC study of selumetinib for recurrent/progressive pediatric low-grade glioma: Strata 2, 5, and 6 with long-term outcomes on strata 1, 3, and 4."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Selumetinib provided stability and responses across many pLGG subgroups,
      and some patients achieved prolonged disease control without additional therapy.
    explanation: >-
      Supports selumetinib as an active targeted therapy across recurrent/progressive
      pediatric low-grade glioma subgroups that include PA.
  - reference: PMID:33631016
    reference_title: "A phase II trial of selumetinib in children with recurrent optic pathway and hypothalamic low-grade glioma without NF1: a Pediatric Brain Tumor Consortium study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Selumetinib was tolerable and led to responses and prolonged disease
      stability in children with recurrent/progressive OPHGs based upon
      radiographic response, PFS, and visual outcomes.
    explanation: >-
      Supports selumetinib specifically in the optic pathway/hypothalamic subset
      where functional visual outcomes are central.
- name: Tovorafenib
  description: >-
    Tovorafenib is an FDA-approved type II RAF inhibitor for relapsed or
    refractory pediatric low-grade glioma with BRAF fusion, rearrangement, or
    V600E mutation, making it directly relevant to recurrent BRAF-altered PA.
  treatment_term:
    preferred_term: targeted therapy
    term:
      id: NCIT:C93352
      label: Targeted Therapy
    therapeutic_agent:
    - preferred_term: tovorafenib
      term:
        id: NCIT:C106254
        label: Tovorafenib
  target_mechanisms:
  - target: Constitutive MAPK Cascade Activation
    treatment_effect: INHIBITS
    description: Type II RAF inhibition targets the upstream RAF/MAPK dependency in BRAF-altered PA.
  evidence:
  - reference: NCIT:C106254
    reference_title: "Tovorafenib (NCIT)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Tovorafenib | Accepted_Therapeutic_Use_For | - | - | for patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation."
    explanation: >-
      NCI Thesaurus asserts accepted therapeutic use of tovorafenib for relapsed
      or refractory pediatric low-grade glioma with BRAF alteration; pilocytic
      astrocytoma is the prototypical BRAF-fusion pediatric low-grade glioma.
  - reference: PMID:39412085
    reference_title: "Type II RAF inhibitor tovorafenib for the treatment of pediatric low-grade glioma."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      On 23 April 2024, the U.S. FDA approved a new type II RAF inhibitor,
      tovorafenib (OJEMDATM), previously known as DAY101, for the treatment of
      patients aged 6 months and older with relapsed or refractory (R/R) pLGG
      harboring a BRAF fusion or rearrangement, or BRAF V600E mutation.
    explanation: >-
      Review-level evidence supports current clinical use of tovorafenib in
      recurrent BRAF-altered pediatric low-grade glioma, a setting directly
      relevant to many recurrent PA cases.
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0016691
      label: pilocytic astrocytoma
    mapping_predicate: skos:exactMatch
    mapping_source: MONDO
    mapping_justification: Primary MONDO disease anchor for the pilocytic astrocytoma mechanism graph.
  ncit_mappings:
  - term:
      id: NCIT:C4047
      label: Pilocytic Astrocytoma
    mapping_predicate: skos:exactMatch
    mapping_source: NCIT
    mapping_justification: NCIT oncology disease mapping retained alongside MONDO per cancer curation guidance.
datasets:
- accession: ega:EGAS00001002149
  title: RNA-sequencing of six Pilocytic astrocytoma tumors
  description: Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. A recurrent feature of PA is deregulation of the mitogen activated protein kinase (MAPK) pathway most often through KIAA1549-BRAF fusion, but also by other BRAF- or RAF1-gene fusions and point mutations (e.g. BRAFV600E). These features may serve as diagnostic and prognostic markers, and also facilitate development of targeted therapy. The aim of this study was to characterize the genetic alterations underlying the development of PA tumor in six cases, and evaluate methods for fusion oncogene detection.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  publication: PMID:28448514
  notes: 'European Genome-phenome Archive study, matched because the disease is named in the study''s own title ("Pilocytic Astrocytoma"); 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:EGAS00001006388
  title: Detection and genomic analysis of BRAF fusions in Juvenile Pilocytic Astrocytoma through the combination and integration of multi-omic data
  description: Juvenile Pilocytic Astrocytoma (JPAs) are highly vascular tumors and show pervasive immune infiltration, which can lead to low tumor cell purity in clinical samples. In some instances, this results in gene fusions that are difficult to detect with conventional omics approaches including RNA-Seq. To this effect, we applied RNA-Seq as well as linked-read whole-genome sequencing and in situ Hi-C as new approaches to detect and characterize low-frequency gene fusions at the genomic, transcriptomic and spatial level. Overall, we demonstrate the power of integrating multi-omic datasets to identify low frequency fusions and characterize the JPA genome at high resolution.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  notes: 'European Genome-phenome Archive study, matched because the disease is named in the study''s own title ("Pilocytic Astrocytoma"); 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:EGAS00001006402
  title: Proteogenomics reveals two distinct biological pilocytic astrocytoma subgroups
  description: Pilocytic astrocytoma (PA) is the most common pediatric brain tumor and driven by aberrant MAPK signaling, typically mediated by BRAF alterations. While five-year overall survival rates exceed 95%, tumor recurrence constitutes a major clinical challenge in incompletely resected tumors despite chemotherapeutic or radiation based therapies. Therefore, we used proteogenomics to discern the biological heterogeneity of PA to improve classification of this tumor entity and identify novel therapeutic targets. Our proteogenomics approach integrates RNA sequencing and LC/MS-based proteomic profiling data from a cohort of 58 confirmed, primary PA samples.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  notes: 'European Genome-phenome Archive study, matched because the disease is named in the study''s own title ("Pilocytic Astrocytoma"); 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: dbgap:phs001854
  title: Human Pilocytic Astrocytoma Single Cell RNA Sequencing
  description: Pilocytic astrocytoma (PA), the most common childhood brain tumor, is a low-grade glioma with a single driver BRAF rearrangement. Here, we perform scRNAseq in six PAs using methods that enabled detection of the rearrangement. When compared to higher-grade gliomas, a strikingly higher proportion of the PA cancer cells exhibit a differentiated, astrocyte-like phenotype. A smaller proportion of cells exhibit a progenitor-like phenotype with evidence of proliferation. These express a mitogen-activated protein kinase (MAPK) program that was absent from higher-grade gliomas.
  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 ("Pilocytic Astrocytoma"). Retrieved 2026-08-02.
- accession: dbgap:phs000563
  title: Pilocytic Astrocytoma in NF1
  description: Neurofibromatosis type 1 (NF1) inherited cancer predisposition syndrome is one of the most common autosomal dominant tumor predisposition syndromes in which affected individuals develop brain tumors. These low-grade glial neoplasms (pilocytic astrocytomas) typically arise in children younger than 7 years of age and are hypothesized to result from a combination of germline and acquired somatic NF1 tumor suppressor gene mutations.
  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 ("Pilocytic Astrocytoma"). Retrieved 2026-08-02.