Childhood pilocytic astrocytoma

Summary

Childhood pilocytic astrocytoma (MONDO:0004000) is a disease with 3 cohort genes and 13 clinical trials. Molecularly, BRAF V600E confers sensitivity to Dabrafenib + Trametinib in Pilocytic Astrocytoma (CIViC Level A); 12 further subtype–drug associations are mapped below. Top therapeutic interventions include dabrafenib, tovorafenib, and trametinib.

At a glance

• Cohort genes: 3
• Clinical trials: 13
• Precision-medicine evidence (CIViC): 13 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	childhood pilocytic astrocytoma
Mondo ID	MONDO:0004000
DOID	DOID:6812
NCIT	C4048
UMLS	C1332995
MedGen	232355
GARD	0023771
Is cancer (heuristic)	no

Also known as: childhood pilocytic astrocytoma · paediatric pilocytic astrocytoma · pediatric pilocytic astrocytoma · pilocytic astrocytoma · pilocytic astrocytoma of childhood

Data availability: 7 cell lines · 42 intOGen driver records.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › childhood neoplasm › childhood astrocytic tumor › childhood pilocytic astrocytoma

Related subtypes (3): childhood cerebellar astrocytic neoplasm, childhood brainstem astrocytoma, childhood cerebral astrocytoma

Subtypes (1): juvenile pilocytic astrocytoma

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 39 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BRAF	Orphanet:1340	Cardiofaciocutaneous syndrome
BRAF	Orphanet:146	Differentiated thyroid carcinoma
BRAF	Orphanet:251615	Pilomyxoid astrocytoma
BRAF	Orphanet:389	Langerhans cell histiocytosis
BRAF	Orphanet:500	Noonan syndrome with multiple lentigines
BRAF	Orphanet:54595	Craniopharyngioma
BRAF	Orphanet:58017	Classic hairy cell leukemia
BRAF	Orphanet:626	Large/giant congenital melanocytic nevus
BRAF	Orphanet:648	Noonan syndrome
BRAF	Orphanet:840	Syringocystadenoma papilliferum
BRAF	Orphanet:96253	Cushing disease
FGFR1	Orphanet:168953	Myeloid/lymphoid neoplasm associated with FGFR1 rearrangement
FGFR1	Orphanet:2117	Hartsfield syndrome
FGFR1	Orphanet:220386	Semilobar holoprosencephaly
FGFR1	Orphanet:2396	Encephalocraniocutaneous lipomatosis
FGFR1	Orphanet:251576	Gliosarcoma
FGFR1	Orphanet:251579	Giant cell glioblastoma
FGFR1	Orphanet:251615	Pilomyxoid astrocytoma
FGFR1	Orphanet:2645	Osteoglosphonic dysplasia
FGFR1	Orphanet:280200	Microform holoprosencephaly
FGFR1	Orphanet:314950	Primary hypereosinophilic syndrome
FGFR1	Orphanet:3157	Septo-optic dysplasia spectrum
FGFR1	Orphanet:3366	Non-syndromic metopic craniosynostosis
FGFR1	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
FGFR1	Orphanet:478	Kallmann syndrome
FGFR1	Orphanet:93258	Pfeiffer syndrome type 1
FGFR1	Orphanet:93924	Lobar holoprosencephaly
FGFR1	Orphanet:99798	Oligodontia
KRAS	Orphanet:1333	Familial pancreatic carcinoma
KRAS	Orphanet:1340	Cardiofaciocutaneous syndrome
KRAS	Orphanet:144	Lynch syndrome
KRAS	Orphanet:146	Differentiated thyroid carcinoma
KRAS	Orphanet:2396	Encephalocraniocutaneous lipomatosis
KRAS	Orphanet:251615	Pilomyxoid astrocytoma
KRAS	Orphanet:2612	Linear nevus sebaceus syndrome
KRAS	Orphanet:268114	RAS-associated autoimmune leukoproliferative disease
KRAS	Orphanet:3339	Oculoectodermal syndrome
KRAS	Orphanet:648	Noonan syndrome
KRAS	Orphanet:86834	Juvenile myelomonocytic leukemia

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	civic_evidence
FGFR1	HGNC:3688	ENSG00000077782	P11362	Fibroblast growth factor receptor 1	civic_evidence
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
FGFR1	Fibroblast growth factor receptor 1	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration.
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	2	18.5×	0.008
Enzyme (other)	1	4.0×	0.230

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
FGFR1	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	2
calcaneal tendon	2
colonic epithelium	1
stromal cell of endometrium	1
nipple	1
pylorus	1
trigeminal ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
FGFR1	292	ubiquitous	marker	buccal mucosa cell, stromal cell of endometrium, calcaneal tendon
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KRAS	14,509
BRAF	7,394
FGFR1	5,693

Intra-cohort edges

A	B	Sources
BRAF	KRAS	biogrid_interaction, intact, string_interaction

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
BRAF	P15056	131
FGFR1	P11362	83

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 116. Enrichment computed across 3 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
SHC-mediated cascade:FGFR1	2	331.0×	4e-04	FGFR1, KRAS
FRS-mediated FGFR1 signaling	2	304.5×	4e-04	FGFR1, KRAS
Negative regulation of FGFR1 signaling	2	245.6×	4e-04	BRAF, FGFR1
RAF activation	2	223.9×	4e-04	BRAF, KRAS
Signaling by high-kinase activity BRAF mutants	2	211.5×	4e-04	BRAF, KRAS
Signaling by FGFR1 in disease	2	195.2×	4e-04	FGFR1, KRAS
MAP2K and MAPK activation	2	190.3×	4e-04	BRAF, KRAS
Signaling by RAF1 mutants	2	185.7×	4e-04	BRAF, KRAS
NCAM signaling for neurite out-growth	2	181.3×	4e-04	FGFR1, KRAS
Negative regulation of MAPK pathway	2	177.1×	4e-04	BRAF, KRAS
Signaling by moderate kinase activity BRAF mutants	2	169.2×	4e-04	BRAF, KRAS
Paradoxical activation of RAF signaling by kinase inactive BRAF	2	169.2×	4e-04	BRAF, KRAS
Signaling downstream of RAS mutants	2	169.2×	4e-04	BRAF, KRAS
RAF/MAP kinase cascade	3	61.1×	4e-04	BRAF, FGFR1, KRAS
Signaling by BRAF and RAF1 fusions	2	113.6×	8e-04	BRAF, KRAS
Signaling by FGFR1 amplification mutants	1	1903.3×	0.004	FGFR1
Signaling by RAS GAP mutants	1	1268.9×	0.005	KRAS
Signaling by RAS GTPase mutants	1	1268.9×	0.005	KRAS
FGFR1c and Klotho ligand binding and activation	1	951.7×	0.006	FGFR1
Signaling by plasma membrane FGFR1 fusions	1	951.7×	0.006	FGFR1
Signaling by MRAS-complex mutants	1	951.7×	0.006	BRAF
Activation of RAS in B cells	1	761.3×	0.007	KRAS
Signalling to p38 via RIT and RIN	1	761.3×	0.007	BRAF
Negative feedback regulation of MAPK pathway	1	634.4×	0.008	BRAF
ARMS-mediated activation	1	543.8×	0.008	BRAF
RAS signaling downstream of NF1 loss-of-function variants	1	543.8×	0.008	KRAS
Estrogen-stimulated signaling through PRKCZ	1	543.8×	0.008	KRAS
SOS-mediated signalling	1	475.8×	0.008	KRAS
Prolonged ERK activation events	1	475.8×	0.008	BRAF
SHOC2 M1731 mutant abolishes MRAS complex function	1	475.8×	0.008	BRAF

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
MAPK cascade	3	153.2×	4e-05	BRAF, FGFR1, KRAS
cardiac muscle cell proliferation	2	387.4×	6e-04	FGFR1, KRAS
visual learning	2	204.3×	0.001	BRAF, KRAS
response to mineralocorticoid	1	5617.3×	0.005	KRAS
vitamin D3 metabolic process	1	2808.7×	0.005	FGFR1
positive regulation of mitotic cell cycle DNA replication	1	2808.7×	0.005	FGFR1
positive regulation of parathyroid hormone secretion	1	2808.7×	0.005	FGFR1
regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	2808.7×	0.005	FGFR1
regulation of phosphate transport	1	1872.4×	0.005	FGFR1
forebrain astrocyte development	1	1872.4×	0.005	KRAS
fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development	1	1872.4×	0.005	FGFR1
CD4-positive or CD8-positive, alpha-beta T cell lineage commitment	1	1872.4×	0.005	BRAF
regulation of lateral mesodermal cell fate specification	1	1872.4×	0.005	FGFR1
negative regulation of neuron apoptotic process	2	73.9×	0.005	BRAF, KRAS
gene expression	2	53.2×	0.005	FGFR1, KRAS
ventricular zone neuroblast division	1	1404.3×	0.005	FGFR1
response to isolation stress	1	1404.3×	0.005	KRAS
negative regulation of fibroblast growth factor production	1	1404.3×	0.005	FGFR1
positive regulation of phospholipase activity	1	1123.5×	0.005	FGFR1
positive regulation of axon regeneration	1	1123.5×	0.005	BRAF
regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling	1	1123.5×	0.005	FGFR1
diphosphate metabolic process	1	1123.5×	0.005	FGFR1
negative regulation of synaptic vesicle exocytosis	1	1123.5×	0.005	BRAF
protein phosphorylation	2	45.3×	0.005	BRAF, FGFR1
response to gravity	1	936.2×	0.005	KRAS
chordate embryonic development	1	936.2×	0.005	FGFR1
CD4-positive, alpha-beta T cell differentiation	1	936.2×	0.005	BRAF
positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway	1	936.2×	0.005	FGFR1
myeloid progenitor cell differentiation	1	802.5×	0.005	BRAF
cementum mineralization	1	802.5×	0.005	FGFR1

Therapeutics

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 0

Druggability breadth: 3 of 3 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
BRAF	VEMURAFENIB
FGFR1	PONATINIB
KRAS	VEMURAFENIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FGFR1	93	4
BRAF	48	4
KRAS	11	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VEMURAFENIB	4	BRAF, KRAS
PONATINIB	4	BRAF, FGFR1
FEDRATINIB	4	BRAF, FGFR1
SORAFENIB	4	BRAF, FGFR1
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF, FGFR1
INFIGRATINIB	4	BRAF, FGFR1
REGORAFENIB	4	BRAF, FGFR1
DABRAFENIB	4	BRAF, KRAS
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF
ABEMACICLIB	4	BRAF
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	BRAF, FGFR1
DASATINIB	4	BRAF, FGFR1
ERLOTINIB	4	BRAF
GEFITINIB	4	BRAF
IMATINIB	4	BRAF
PEMIGATINIB	4	FGFR1
NINTEDANIB	4	FGFR1
TIVOZANIB	4	FGFR1
LENVATINIB	4	FGFR1
AXITINIB	4	FGFR1
NICLOSAMIDE	4	FGFR1
ENTRECTINIB	4	FGFR1
CABOZANTINIB	4	FGFR1
CAPIVASERTIB	4	FGFR1
VANDETANIB	4	FGFR1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
FGFR1	1,465	Binding:1428, Functional:24, ADMET:13
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
KRAS	861	Binding:829, Functional:32

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
FGFR1	2.7.10.1	receptor protein-tyrosine kinase
KRAS	3.6.5.2	small monomeric GTPase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
BRAF	1,442
FGFR1	1,465
KRAS	861

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

28 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
VEMURAFENIB	4	BRAF, KRAS
PONATINIB	4	BRAF, FGFR1
FEDRATINIB	4	BRAF, FGFR1
SORAFENIB	4	BRAF, FGFR1
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF, FGFR1
INFIGRATINIB	4	BRAF, FGFR1
REGORAFENIB	4	BRAF, FGFR1
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF
ABEMACICLIB	4	BRAF
ENCORAFENIB	4	BRAF
PAZOPANIB	4	BRAF, FGFR1
DASATINIB	4	BRAF, FGFR1
ERLOTINIB	4	BRAF
GEFITINIB	4	BRAF
IMATINIB	4	BRAF
PEMIGATINIB	4	FGFR1
NINTEDANIB	4	FGFR1
TIVOZANIB	4	FGFR1
LENVATINIB	4	FGFR1
AXITINIB	4	FGFR1
NICLOSAMIDE	4	FGFR1
ENTRECTINIB	4	FGFR1
CABOZANTINIB	4	FGFR1
CAPIVASERTIB	4	FGFR1
VANDETANIB	4	FGFR1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	BRAF, FGFR1, KRAS
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 13.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	4
Not specified	4
PHASE1/PHASE2	2
PHASE1	2
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03975829	PHASE4	RECRUITING	Pediatric Long-Term Follow-up and Rollover Study
NCT01089101	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
NCT01553149	PHASE2	COMPLETED	Low-Dose or High-Dose Lenalidomide in Treating Younger Patients With Recurrent, Refractory, or Progressive Pilocytic Astrocytoma or Optic Pathway Glioma
NCT01837862	PHASE1/PHASE2	COMPLETED	A Phase I Study of Mebendazole for the Treatment of Pediatric Gliomas
NCT02372409	PHASE2	TERMINATED	Using MRI-Guided Laser Heat Ablation to Induce Disruption of the Peritumoral Blood Brain Barrier to Enhance Delivery and Efficacy of Treatment of Pediatric Brain Tumors
NCT02684058	PHASE2	COMPLETED	Study of Efficacy and Safety of Dabrafenib in Combination With Trametinib in Pediatric Patients With BRAF V600 Mutation Positive LGG or Relapsed or Refractory HGG Tumors
NCT04985604	PHASE2	TERMINATED	Tovorafenib (DAY101) Monotherapy for Patients With Melanoma and Other Solid Tumors
NCT04541082	PHASE1	RECRUITING	Phase I Study of Oral ONC206 in Recurrent and Rare Primary Central Nervous System Neoplasms
NCT07121829	PHASE1	TERMINATED	Tovorafenib (DAY101) or in Combination With Pimasertib for Participants With Melanoma and Other Solid Tumors
NCT04065776	Not specified	RECRUITING	Evaluation of Hippocampal-Avoidance Using Proton Therapy in Low-Grade Glioma
NCT06915649	Not specified	RECRUITING	Exploration and Evaluation of Amygdalo-Hippocampectomy According to Prof. Coubes’ Technique: An Anatomical, Clinical, and Educational Approach
NCT02194452	Not specified	WITHDRAWN	Efficacy of 68Ga-DOTATOC Positron Emission Tomography (PET) CT in Children and Young Adults With Brain Tumors
NCT05934630	Not specified	TERMINATED	Testing Cerebrospinal Fluid for Cell-free Tumor DNA in Children, Adolescents, and Young Adults With Brain Tumors

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DABRAFENIB	4	2
TOVORAFENIB	4	2
TRAMETINIB	4	2
EDOTREOTIDE GALLIUM GA-68	4	1
MEBENDAZOLE	4	1
SELUMETINIB	4	1
ONC-206	1	1
CHEMBL5433950	0	2
CHEMBL4463209	0	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 13 predictive associations from 14 curated evidence items; also 8 diagnostic, 2 oncogenic.

Molecular subtype	Therapy	Effect	Level	CIViC
BRAF V600E	Dabrafenib + Trametinib	Sensitivity/Response	CIViC A	EID11313
KIAA1549::BRAF Fusion	Selumetinib	Sensitivity/Response	CIViC B	EID7486 +1
BRAF V600E	Selumetinib	Sensitivity/Response	CIViC B	EID7485
BRAF V600E OR KIAA1549::BRAF Fusion	Selumetinib	Sensitivity/Response	CIViC B	EID11316
BRAF V600E	Vemurafenib	Sensitivity/Response	CIViC C	EID3772
BRAF V600E	Vemurafenib	Sensitivity/Response	CIViC C	EID3777
FGFR1 N546K	Pemigatinib	Sensitivity/Response	CIViC C	EID10325
GOPC::ROS1 Fusion	Entrectinib	Sensitivity/Response	CIViC C	EID12604
NF1 Mutation AND Methylation signature PA-NF1	Trametinib	Sensitivity/Response	CIViC C	EID12269
NF1 Splice Site (c.205-1G>C) AND NF1 G629R	Vincristine + Carboplatin + Trametinib + Selumetinib	Sensitivity/Response	CIViC C	EID12271
BRAF T599dup			CIViC C	EID2990
KIAA1549::BRAF Fusion	Trametinib	Sensitivity/Response	CIViC D	EID8944
KIAA1549::BRAF Fusion	Vemurafenib + Sorafenib	Resistance	CIViC D	EID7402