Primitive neuroectodermal tumor

Summary

Primitive neuroectodermal tumor (MONDO:0005462) is a cancer (an umbrella term covering 5 Mondo subtypes) with 1 cohort gene (1 CIViC-evidence somatic driver; 1 ClinVar predisposition record) and 37 clinical trials. Top therapeutic interventions include carboplatin, afatinib, and aminolevulinic acid.

At a glance

• Classification: Cancer
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 37

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primitive neuroectodermal tumor
Mondo ID	MONDO:0005462
EFO	EFO:0005235
MeSH	D017599
DOID	DOID:171
NCIT	C3716
UMLS	C0206663
MedGen	64627
Is cancer (heuristic)	yes

Also known as: neuroectodermal neoplasm · neuroectodermal tumor · neuroectodermal tumour · PNET · primitive neuroectodermal neoplasm · primitive neuroectodermal tumor · primitive neuroectodermal tumor (PNET) · primitive neuroectodermal tumour (PNET)

Data availability: 1 ClinVar variant · 35 cell lines.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › embryonal neoplasm › primitive neuroectodermal tumor

Related subtypes (11): notochordal tumor, rhabdoid tumor, blastoma, Wilms tumor, testicular embryonal carcinoma, medulloblastoma, pineoblastoma, congenital mesoblastic nephroma, intraocular medulloepithelioma, hepatoblastoma, Ewing sarcoma/peripheral primitive neuroectodermal tumor

Subtypes (5): central nervous system primitive neuroectodermal neoplasm, melanotic neuroectodermal tumor, neuroblastic tumor, primitive neuroectodermal tumor of the corpus uteri, peripheral primitive neuroectodermal tumor

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

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
41690	NM_000368.5(TSC1):c.1460C>G (p.Ser487Cys)	TSC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
TSC1	LoF	BLCA,BRCA,COADREAD,HCC,LUAD,RCC,SKCM,STAD,UTUC	CIViC #46

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TSC1	Orphanet:210159	Adult hepatocellular carcinoma
TSC1	Orphanet:269008	Isolated focal cortical dysplasia type IIb
TSC1	Orphanet:538	Lymphangioleiomyomatosis
TSC1	Orphanet:805	Tuberous sclerosis complex

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TSC1	HGNC:12362	ENSG00000165699	Q92574	Hamartin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TSC1	Hamartin	Non-catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolec…

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TSC1	Other/Unknown	no		Hamartin

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gluteal muscle	1
lateral globus pallidus	1
substantia nigra pars compacta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TSC1	297	ubiquitous	marker	substantia nigra pars compacta, gluteal muscle, lateral globus pallidus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TSC1	5,445

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TSC1	Q92574	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Inhibition of TSC complex formation by AKT (PKB)	1	2284.0×	0.002	TSC1
Energy dependent regulation of mTOR by LKB1-AMPK	1	393.8×	0.006	TSC1
TBC/RABGAPs	1	259.6×	0.006	TSC1
TP53 Regulates Metabolic Genes	1	129.8×	0.009	TSC1
Macroautophagy	1	115.3×	0.009	TSC1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
memory T cell differentiation	1	5617.3×	0.004	TSC1
cellular response to decreased oxygen levels	1	4213.0×	0.004	TSC1
negative regulation of ATP-dependent activity	1	1685.2×	0.004	TSC1
negative regulation of cell size	1	1685.2×	0.004	TSC1
regulation of cell-matrix adhesion	1	1296.3×	0.004	TSC1
negative regulation of macroautophagy	1	1123.5×	0.004	TSC1
regulation of stress fiber assembly	1	991.3×	0.004	TSC1
obsolete D-glucose import	1	842.6×	0.004	TSC1
activation of GTPase activity	1	732.7×	0.004	TSC1
cardiac muscle cell differentiation	1	674.1×	0.004	TSC1
positive regulation of focal adhesion assembly	1	648.1×	0.004	TSC1
negative regulation of TOR signaling	1	561.7×	0.005	TSC1
associative learning	1	481.5×	0.005	TSC1
cell projection organization	1	374.5×	0.006	TSC1
negative regulation of TORC1 signaling	1	324.1×	0.006	TSC1
adult locomotory behavior	1	300.9×	0.006	TSC1
synapse organization	1	280.9×	0.006	TSC1
myelination	1	251.5×	0.007	TSC1
hippocampus development	1	230.8×	0.007	TSC1
response to insulin	1	230.8×	0.007	TSC1
cerebral cortex development	1	205.5×	0.007	TSC1
cellular response to starvation	1	193.7×	0.007	TSC1
potassium ion transport	1	191.5×	0.007	TSC1
neural tube closure	1	187.2×	0.007	TSC1
cell-matrix adhesion	1	163.6×	0.008	TSC1
kidney development	1	140.4×	0.008	TSC1
cell population proliferation	1	102.8×	0.011	TSC1
adaptive immune response	1	84.3×	0.013	TSC1
regulation of cell cycle	1	74.6×	0.014	TSC1
protein stabilization	1	66.9×	0.015	TSC1

Therapeutics

Drugs indicated for this disease

0 approved, 6 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Carboplatin	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Etoposide	Phase 3 (in late-stage trials)
Filgrastim	Phase 3 (in late-stage trials)
Methotrexate	Phase 3 (in late-stage trials)
Thiotepa	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): ANTINEOPLASTON A10, Tipifarnib.

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TSC1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

0 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	1	TSC1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TSC1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 37.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1	13
PHASE2	11
Not specified	9
PHASE1/PHASE2	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06638931	PHASE2	RECRUITING	Agnostic Therapy in Rare Solid Tumors
NCT07167329	PHASE2	RECRUITING	Real-World Effectiveness and Pharmacogenetics of Belzutifan in VHL Syndrome: The BELIEVE-VHL Trial
NCT00003515	PHASE2	TERMINATED	Antineoplaston Therapy in Treating Patients With Metastatic, Recurrent, or Refractory Primitive Neuroectodermal Tumors
NCT00831844	PHASE2	COMPLETED	Cixutumumab in Treating Patients With Relapsed or Refractory Solid Tumors
NCT00983398	PHASE1/PHASE2	UNKNOWN	Melphalan, Carboplatin, Mannitol, and Sodium Thiosulfate in Treating Patients With Recurrent or Progressive CNS Embryonal or Germ Cell Tumors
NCT01217437	PHASE2	COMPLETED	Temozolomide and Irinotecan Hydrochloride With or Without Bevacizumab in Treating Young Patients With Recurrent or Refractory Medulloblastoma or CNS Primitive Neuroectodermal Tumors
NCT01222767	PHASE2	COMPLETED	Study of Zalypsis® (PM00104) in Patients With Unresectable Locally Advanced and/or Metastatic Ewing Family of Tumors (EFT) Progressing After at Least One Prior Line of Chemotherapy
NCT01326104	PHASE2	COMPLETED	Vaccine Immunotherapy for Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor
NCT01542736	PHASE2	COMPLETED	Concurrent Carboplatin and Reduced Dose Craniospinal Radiation for Medulloblastoma and Primitive Neuroectodermal Tumor (PNET)
NCT02372006	PHASE1/PHASE2	COMPLETED	Trial of Afatinib in Pediatric Tumours
NCT02689336	PHASE2	WITHDRAWN	Erlotinib in Combination With Temozolomide in Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors
NCT02798406	PHASE2	COMPLETED	Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects
NCT03037385	PHASE1/PHASE2	COMPLETED	Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Participants With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors
NCT03561259	PHASE2	UNKNOWN	A Study of Therapeutic Iobenguane (131-I) and Vorinostat for Recurrent or Progressive High-Risk Neuroblastoma Subjects
NCT04388033	PHASE1/PHASE2	UNKNOWN	Clinical Study of an Dendritic and Glioma Cells Fusion Vaccine With IL-12 for Treatment-naïve GBM Patients.
NCT02508038	PHASE1	RECRUITING	Alpha/Beta CD19+ Depleted Haploidentical Transplantation + Zometa for Pediatric Hematologic Malignancies and Solid Tumors
NCT03500991	PHASE1	ACTIVE_NOT_RECRUITING	HER2-specific CAR T Cell Locoregional Immunotherapy for HER2-positive Recurrent/Refractory Pediatric CNS Tumors
NCT03911388	PHASE1	RECRUITING	HSV G207 in Children With Recurrent or Refractory Cerebellar Brain Tumors
NCT04185038	PHASE1	RECRUITING	Study of B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma/Diffuse Midline Glioma and Recurrent or Refractory Pediatric Central Nervous System Tumors
NCT04541082	PHASE1	RECRUITING	Phase I Study of Oral ONC206 in Recurrent and Rare Primary Central Nervous System Neoplasms
NCT00513162	PHASE1	COMPLETED	Valproate and Etoposide for Patients With Neuronal Tumors and Brain Metastases
NCT00994071	PHASE1	COMPLETED	A Phase I Study of ABT-888, an Oral Inhibitor of Poly(ADP-ribose) Polymerase and Temozolomide in Children With Recurrent/Refractory CNS Tumors
NCT02110563	PHASE1	TERMINATED	Phase I, Multicenter, Dose Escalation Study of DCR-MYC in Patients With Solid Tumors, Multiple Myeloma, or Lymphoma
NCT02444546	PHASE1	COMPLETED	Wild-Type Reovirus in Combination With Sargramostim in Treating Younger Patients With High-Grade Relapsed or Refractory Brain Tumors
NCT02457845	PHASE1	COMPLETED	HSV G207 Alone or With a Single Radiation Dose in Children With Progressive or Recurrent Supratentorial Brain Tumors
NCT03434262	PHASE1	COMPLETED	SJDAWN: St. Jude Children’s Research Hospital Phase 1 Study Evaluating Molecularly-Driven Doublet Therapies for Children and Young Adults With Recurrent Brain Tumors
NCT03638167	PHASE1	COMPLETED	EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric CNS Tumors
NCT04521946	PHASE1	WITHDRAWN	Chemotherapy and Donor Stem Transplant for the Treatment of Patients With High Grade Brain Cancer
NCT04949282	Not specified	RECRUITING	Spanish Series of Patients Treated With the Radionuclide Lutetium177
NCT05850377	Not specified	NOT_YET_RECRUITING	5-Aminolevulinic Acid (5-ALA) Gliolan®: Usage Increase Proposal for Neurosurgical Procedures in High-Grade Gliomas
NCT00686387	Not specified	UNKNOWN	Establishment of a Brain and Spinal Tumor Tissue Bank
NCT01117155	Not specified	WITHDRAWN	A Pilot Study Evaluating 18F-L-Thymidine (FLT) PET Imaging in Children With Gliomas
NCT01251913	Not specified	TERMINATED	A Pilot Study of Inpatient Hospice With Procurement of Brain Tumor Tissue on Expiration for Research Purposes
NCT01445288	Not specified	COMPLETED	Exploratory Study of Effects of Radiation Therapy in Pediatric Patients With Central Nervous System Tumors
NCT01579253	Not specified	UNKNOWN	Combined O-(2-[18F]Fluoroethyl)-L-tyrosine (FET) Positron Emission Tomography (PET) and Simultaneous Magnetic Resonance Imaging (MRI) Follow-up in Re-irradiated Recurrent Glioblastoma Patients
NCT03251989	Not specified	COMPLETED	Rare CNS Tumors Outcomes &Risk
NCT05592743	Not specified	APPROVED_FOR_MARKETING	Vorasidenib Expanded Access Program

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CARBOPLATIN	4	2
AFATINIB	4	1
AMINOLEVULINIC ACID	4	1
BELZUTIFAN	4	1
IOBENGUANE I 131	4	1
MANNITOL	4	1
PRALSETINIB	4	1
SODIUM THIOSULFATE	4	1
SONIDEGIB	4	1
SORBITOL	4	1
VALPROIC ACID	4	1
VORASIDENIB	4	1
ZOLEDRONIC ACID ANHYDROUS	4	1
VELIPARIB	3	1
CIXUTUMUMAB	2	1
INTERLEUKIN-12 HUMAN RECOMBINANT	2	1
PM-00104	2	1
TASADENOTUREV	2	1
ONC-206	1	1
CHEMBL3753202	0	1
CHEMBL2347958	0	1
CHEMBL4283673	0	1
CHEMBL4759112	0	1
CHEMBL4297597	0	1
CHEMBL4278845	0	1