Childhood epithelioid sarcoma

Summary

Childhood epithelioid sarcoma (MONDO:0004105) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver) and 27 clinical trials. Molecularly, SMARCB1 Deletion confers sensitivity to Tazemetostat in Epithelioid Sarcoma (CIViC Level A); 1 further subtype–drug associations are mapped below. Top therapeutic interventions include tazemetostat, dexrazoxane, and ifosfamide.

At a glance

• Classification: Cancer
• Cohort genes: 1
• Clinical trials: 27
• Precision-medicine evidence (CIViC): 2 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	childhood epithelioid sarcoma
Mondo ID	MONDO:0004105
DOID	DOID:7095
NCIT	C8095
UMLS	C0279989
MedGen	76055
GARD	0023826
Is cancer (heuristic)	yes

Also known as: childhood epithelioid sarcoma · epithelioid sarcoma · epithelioid sarcoma of childhood · paediatric epithelioid sarcoma · pediatric epithelioid sarcoma

Data availability: 22 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › childhood malignant neoplasm › childhood epithelioid sarcoma

Related subtypes (29): childhood oligodendroglioma, pediatric osteosarcoma, pediatric fibrosarcoma, childhood choroid plexus carcinoma, childhood central nervous system primitive neuroectodermal neoplasm, childhood brain stem neoplasm, pediatric angiosarcoma, pediatric mesenchymal chondrosarcoma, pediatric liposarcoma, pediatric lymphoma, childhood malignant mesenchymoma, pediatric myxoid chondrosarcoma, childhood botryoid rhabdomyosarcoma, pediatric intraocular retinoblastoma, childhood cerebral astrocytoma, childhood pleomorphic rhabdomyosarcoma, pediatric infratentorial ependymoma, pediatric supratentorial ependymoma, childhood malignant schwannoma, pediatric extraocular retinoblastoma, childhood leukemia, childhood precursor T-lymphoblastic lymphoma/leukemia, malignant childhood germ cell neoplasm, pleuropulmonary blastoma, pediatric hepatocellular carcinoma, childhood malignant kidney neoplasm, childhood malignant melanoma, extrarenal rhabdoid tumor, pediatric high-grade glioma

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: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
SMARCB1	Act	ATRT,MBL,NBL,PANET,PAST	CIViC #5356

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SMARCB1	Orphanet:1465	Coffin-Siris syndrome
SMARCB1	Orphanet:231108	Rhabdoid tumor predisposition syndrome
SMARCB1	Orphanet:2495	Meningioma
SMARCB1	Orphanet:263662	Familial multiple meningioma
SMARCB1	Orphanet:93921	Full schwannomatosis
SMARCB1	Orphanet:99966	Atypical teratoid rhabdoid tumor

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SMARCB1	HGNC:11103	ENSG00000099956	Q12824	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SMARCB1	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1	Core component of the BAF (hSWI/SNF) complex.

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)
SMARCB1	Other/Unknown	no		SNF5, Sfh1/SNF5, INI1_DNA-bd

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
cortical plate	1
embryo	1
ganglionic eminence	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SMARCB1	214	ubiquitous	marker	embryo, ganglionic eminence, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMARCB1	5,083

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SMARCB1	Q12824	17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. 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
Formation of the canonical BAF (cBAF) complex	1	634.4×	0.010	SMARCB1
Formation of the polybromo-BAF (pBAF) complex	1	634.4×	0.010	SMARCB1
Formation of the embryonic stem cell BAF (esBAF) complex	1	601.0×	0.010	SMARCB1
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	456.8×	0.010	SMARCB1
Regulation of endogenous retroelements	1	368.4×	0.010	SMARCB1
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	300.5×	0.010	SMARCB1
Regulation of MITF-M-dependent genes involved in pigmentation	1	265.6×	0.010	SMARCB1
MITF-M-dependent gene expression	1	181.3×	0.013	SMARCB1
RMTs methylate histone arginines	1	146.4×	0.013	SMARCB1
Transcriptional regulation by RUNX1	1	146.4×	0.013	SMARCB1
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	1	117.7×	0.014	SMARCB1
MITF-M-regulated melanocyte development	1	114.2×	0.014	SMARCB1
Chromatin organization	1	81.6×	0.018	SMARCB1
Chromatin modifying enzymes	1	72.3×	0.018	SMARCB1
Epigenetic regulation of gene expression	1	71.4×	0.018	SMARCB1
RNA Polymerase II Transcription	1	22.5×	0.053	SMARCB1
Gene expression (Transcription)	1	17.8×	0.063	SMARCB1
Generic Transcription Pathway	1	15.1×	0.069	SMARCB1
Developmental Biology	1	14.5×	0.069	SMARCB1

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
single stranded viral RNA replication via double stranded DNA intermediate	1	16852.0×	0.001	SMARCB1
positive regulation of glucose mediated signaling pathway	1	5617.3×	0.002	SMARCB1
RNA polymerase I preinitiation complex assembly	1	3370.4×	0.002	SMARCB1
DNA integration	1	2106.5×	0.003	SMARCB1
positive regulation of transcription of nucleolar large rRNA by RNA polymerase I	1	1532.0×	0.003	SMARCB1
hepatocyte differentiation	1	1203.7×	0.003	SMARCB1
host-mediated activation of viral transcription	1	887.0×	0.004	SMARCB1
nucleosome disassembly	1	802.5×	0.004	SMARCB1
regulation of G0 to G1 transition	1	674.1×	0.004	SMARCB1
regulation of nucleotide-excision repair	1	601.9×	0.004	SMARCB1
blastocyst hatching	1	543.6×	0.004	SMARCB1
regulation of mitotic metaphase/anaphase transition	1	495.6×	0.004	SMARCB1
positive regulation of T cell differentiation	1	455.5×	0.004	SMARCB1
transcription initiation-coupled chromatin remodeling	1	383.0×	0.004	SMARCB1
positive regulation of myoblast differentiation	1	366.4×	0.004	SMARCB1
positive regulation of stem cell population maintenance	1	343.9×	0.004	SMARCB1
positive regulation of double-strand break repair	1	343.9×	0.004	SMARCB1
regulation of G1/S transition of mitotic cell cycle	1	306.4×	0.004	SMARCB1
positive regulation of cell differentiation	1	267.5×	0.005	SMARCB1
chromatin remodeling	1	73.0×	0.016	SMARCB1
nervous system development	1	45.9×	0.025	SMARCB1
negative regulation of cell population proliferation	1	42.1×	0.026	SMARCB1
positive regulation of transcription by RNA polymerase II	1	14.9×	0.070	SMARCB1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	SMARCB1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SMARCB1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SMARCB1	7	Binding:7

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	SMARCB1

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)
SMARCB1	7	—

Clinical trials & evidence

Clinical trials

Clinical trials: 27.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	8
PHASE2	7
PHASE1/PHASE2	5
PHASE1	5
PHASE3	1
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02180867	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Radiation Therapy With or Without Combination Chemotherapy or Pazopanib Before Surgery in Treating Patients With Newly Diagnosed Non-rhabdomyosarcoma Soft Tissue Sarcomas That Can Be Removed by Surgery
NCT00346164	PHASE3	COMPLETED	Observation, Radiation Therapy, Combination Chemotherapy, and/or Surgery in Treating Young Patients With Soft Tissue Sarcoma
NCT03069378	PHASE2	ACTIVE_NOT_RECRUITING	A Study of Talimogene Laherparepvec (T-VEC) in Combination With Pembrolizumab in Patients With Metastatic and/or Locally Advanced Sarcoma
NCT04390737	PHASE1/PHASE2	RECRUITING	Evaluate the Safety and Clinical Activity of HH2853
NCT04416568	PHASE2	ACTIVE_NOT_RECRUITING	Study of Nivolumab and Ipilimumab in Children and Young Adults With INI1-Negative Cancers
NCT05286801	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory SMARCB1 or SMARCA4 Deficient Tumors
NCT05407441	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Tazemetostat+Nivo/Ipi in INI1-Neg/SMARCA4-Def Tumors
NCT06277154	PHASE2	RECRUITING	MASCT-I Combined With Doxorubicin and Ifosfamide for First-line Treatment of Advanced Soft Tissue Sarcoma
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT00464620	PHASE2	COMPLETED	Trial of Dasatinib in Advanced Sarcomas
NCT01614795	PHASE2	COMPLETED	Cixutumumab and Temsirolimus in Treating Younger Patients With Recurrent or Refractory Sarcoma
NCT02584309	PHASE2	COMPLETED	Doxorubicin With Upfront Dexrazoxane for the Treatment of Advanced or Metastatic Soft Tissue Sarcoma
NCT02601950	PHASE2	COMPLETED	A Study of Tazemetostat in Adult Participants With Soft Tissue Sarcoma
NCT03190174	PHASE1/PHASE2	COMPLETED	Nivolumab (Opdivo®) Plus ABI-009 (Nab-rapamycin) for Advanced Sarcoma and Certain Cancers
NCT00720174	PHASE1	COMPLETED	Cixutumumab and Doxorubicin Hydrochloride in Treating Patients With Unresectable, Locally Advanced, or Metastatic Soft Tissue Sarcoma
NCT03009201	PHASE1	COMPLETED	Ribociclib and Doxorubicin in Treating Patients With Metastatic or Advanced Soft Tissue Sarcomas That Cannot Be Removed by Surgery
NCT04204941	PHASE1	TERMINATED	Tazemetostat in Combination With Doxorubicin as Frontline Therapy for Advanced Epithelioid Sarcoma
NCT04537715	PHASE1	COMPLETED	Effects of Itraconazole and Rifampin on the Blood Tazemetostat Levels
NCT05415098	PHASE1	UNKNOWN	Study of Safety, Pharmacokinetic and Efficacy of APG-5918 in Advanced Solid Tumors or Lymphomas
NCT03099681	Not specified	RECRUITING	An Observational Study on Epithelioid Sarcoma
NCT03967834	Not specified	RECRUITING	Multimodal Immune Characterization of RAre Soft Tissue Sarcoma - MIRAS Project From SARRA (SARcome RAre) Project of the French Sarcoma Group
NCT07502716	Not specified	AVAILABLE	Compassionate Use of Ubamatamab
NCT01567046	Not specified	COMPLETED	Studying Genes in Tissue Samples From Younger and Adolescent Patients With Soft Tissue Sarcomas
NCT03837678	Not specified	COMPLETED	Epithelioid Sarcoma Natural History Study
NCT03874455	Not specified	NO_LONGER_AVAILABLE	Tazemetostat Expanded Access Program for Adults With Solid Tumors
NCT04008238	Not specified	COMPLETED	Prospective Identification of Predictive Biomarkers of Trabectedin Efficacy in Non-L Soft-tissue Sarcoma Patients
NCT04225429	Not specified	NO_LONGER_AVAILABLE	Tazemetostat Expanded Access Program for Adults With Epithelioid Sarcoma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TAZEMETOSTAT	4	6
DEXRAZOXANE	4	3
IFOSFAMIDE	4	3
PAZOPANIB	4	3
DASATINIB ANHYDROUS	4	2
FLUDEOXYGLUCOSE F 18	4	1
TRABECTEDIN	4	1
TIRAGOLUMAB	3	1
CIXUTUMUMAB	2	2
UBAMATAMAB	2	1
CHEMBL5398431	0	6
CHEMBL4068768	0	1
CHEMBL4171277	0	1
CHEMBL4583196	0	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 2 predictive associations from 2 curated evidence items; also 1 oncogenic.

Molecular subtype	Therapy	Effect	Level	CIViC
SMARCB1 Deletion	Tazemetostat	Sensitivity/Response	CIViC A	EID9992
SMARCB1 Loss	Tazemetostat	Sensitivity/Response	CIViC C	EID11181