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Atlas / Disease / Ewing sarcoma of bone

Ewing sarcoma of bone

disease
On this page

Also known as bone Ewing's sarcomabone localised Ewing sarcomabone localised Ewing's sarcomabone tissue Ewing sarcomaEwing's sarcoma of boneEwing's sarcoma, osseousEwing's sarcoma/bone peripheral primitive neuroectodermal tumourlocalised skeletal Ewing's sarcomaosseous Ewing's sarcomaosseous Ewing's tumorosseous Ewing's tumourskeletal Ewing's sarcomaskeletal Ewing's tumorskeletal Ewing's tumour

Summary

Ewing sarcoma of bone (MONDO:0002625) is a cancer with 4 cohort genes (4 CIViC-evidence somatic drivers) and 14 clinical trials. Molecularly, PTPRD V253I confers sensitivity to Cixutumumab + Teprotumumab in Ewing Sarcoma Of Bone (CIViC Level C); 3 further subtype–drug associations are mapped below. Top therapeutic interventions include sodium chloride, topotecan hydrochloride, and elraglusib.

At a glance

  • Classification: Cancer
  • Cohort genes: 4
  • Clinical trials: 14
  • Precision-medicine evidence (CIViC): 4 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameEwing sarcoma of bone
Mondo IDMONDO:0002625
DOIDDOID:3368
NCITC4835
SNOMED CT307608006
UMLSC0585474
MedGen108438
GARD0023194
Anatomy (UBERON)UBERON:0002481
Is cancer (heuristic)yes

Also known as: bone Ewing’s sarcoma · bone localised Ewing sarcoma · bone localised Ewing’s sarcoma · bone tissue Ewing sarcoma · Ewing sarcoma of bone · Ewing’s sarcoma of bone · Ewing’s sarcoma, osseous · Ewing’s sarcoma/bone peripheral primitive neuroectodermal tumour · localised skeletal Ewing’s sarcoma · osseous Ewing’s sarcoma · osseous Ewing’s tumor · osseous Ewing’s tumour · skeletal Ewing’s sarcoma · skeletal Ewing’s tumor · skeletal Ewing’s tumour

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › Ewing sarcoma › Ewing sarcoma of bone

Related subtypes (1): extraskeletal Ewing sarcoma

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

Somatic driver evidence (intOGen + CIViC, cohort fanout)

GeneintOGen roleCancer typesCIViC
STAG2LoFAML,BLCA,CCRCC,ES,GBM,LUSC,MBL,PAST,PRCC,UCEC,WDTCCIViC #8553
CASP8LoFBCC,BLCA,BRCA,CEAD,CESC,CSCC,HNSC,NHL,NPC,STAD,VULVACIViC #761
FGFR1ActBLCA,GBM,OVT,PANCREAS,PAST,PGNG,WDTCCIViC #1885
PTPRDActBRCA,EGC,ESCA,ESCC,LNM,MEL,NHL,OVT,PAAD,SIC,SKCMCIViC #4692

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
STAG2Orphanet:220386Semilobar holoprosencephaly
STAG2Orphanet:521258Xq25 microduplication syndrome
STAG2Orphanet:93925Alobar holoprosencephaly
CASP8Orphanet:210159Adult hepatocellular carcinoma
CASP8Orphanet:275517Autoimmune lymphoproliferative syndrome-recurrent viral infections due to CASP8 deficiency
FGFR1Orphanet:168953Myeloid/lymphoid neoplasm associated with FGFR1 rearrangement
FGFR1Orphanet:2117Hartsfield syndrome
FGFR1Orphanet:220386Semilobar holoprosencephaly
FGFR1Orphanet:2396Encephalocraniocutaneous lipomatosis
FGFR1Orphanet:251576Gliosarcoma
FGFR1Orphanet:251579Giant cell glioblastoma
FGFR1Orphanet:251615Pilomyxoid astrocytoma
FGFR1Orphanet:2645Osteoglosphonic dysplasia
FGFR1Orphanet:280200Microform holoprosencephaly
FGFR1Orphanet:314950Primary hypereosinophilic syndrome
FGFR1Orphanet:3157Septo-optic dysplasia spectrum
FGFR1Orphanet:3366Non-syndromic metopic craniosynostosis
FGFR1Orphanet:432Normosmic congenital hypogonadotropic hypogonadism
FGFR1Orphanet:478Kallmann syndrome
FGFR1Orphanet:93258Pfeiffer syndrome type 1
FGFR1Orphanet:93924Lobar holoprosencephaly
FGFR1Orphanet:99798Oligodontia

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

SubsetGenes
civic_only4

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
STAG2HGNC:11355ENSG00000101972Q8N3U4Cohesin subunit SA-2civic_evidence
CASP8HGNC:1509ENSG00000064012Q14790Caspase-8civic_evidence
FGFR1HGNC:3688ENSG00000077782P11362Fibroblast growth factor receptor 1civic_evidence
PTPRDHGNC:9668ENSG00000153707P23468Receptor-type tyrosine-protein phosphatase deltacivic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
STAG2Cohesin subunit SA-2Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication.
CASP8Caspase-8Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic development and adulthood.
FGFR1Fibroblast growth factor receptor 1Tyrosine-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.
PTPRDReceptor-type tyrosine-protein phosphatase deltaCan bidirectionally induce pre- and post-synaptic differentiation of neurons by mediating interaction with IL1RAP and IL1RAPL1 trans-synaptically.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.75

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.

FamilyGenesFoldFDR
Phosphatase121.0×0.187
Kinase16.9×0.273
Enzyme (other)13.0×0.392
Other/Unknown10.5×0.962

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
STAG2Other/UnknownnoSTAG, ARM-type_fold, SCD
CASP8Enzyme (other)yes3.4.22.61Pept_C14_p20, DED_dom, Pept_C14_p10
FGFR1Kinaseyes2.7.10.1Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
PTPRDPhosphataseyes3.1.3.48PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)4
unknown0

Top tissues across cohort

TissueCohort genes
calcaneal tendon2
mucosa of paranasal sinus1
sural nerve1
leukocyte1
monocyte1
mononuclear cell1
buccal mucosa cell1
stromal cell of endometrium1
cerebellar hemisphere1
cortical plate1
right hemisphere of cerebellum1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
STAG2299ubiquitousmarkermucosa of paranasal sinus, calcaneal tendon, sural nerve
CASP8252ubiquitousmarkermonocyte, mononuclear cell, leukocyte
FGFR1292ubiquitousmarkerbuccal mucosa cell, stromal cell of endometrium, calcaneal tendon
PTPRD160broadmarkercortical plate, right hemisphere of cerebellum, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
FGFR15,693
CASP85,040
PTPRD3,052
STAG22,945

Structural data

PDB: 4 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
FGFR1P1136283
CASP8Q1479036
STAG2Q8N3U49
PTPRDP234688

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 106. Enrichment computed across 4 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Signaling by FGFR1 amplification mutants11427.5×0.020FGFR1
FGFR1c and Klotho ligand binding and activation1713.8×0.020FGFR1
Activation, myristolyation of BID and translocation to mitochondria1713.8×0.020CASP8
Signaling by plasma membrane FGFR1 fusions1713.8×0.020FGFR1
Microbial modulation of RIPK1-mediated regulated necrosis1713.8×0.020CASP8
FasL/ CD95L signaling1571.0×0.020CASP8
CLEC7A/inflammasome pathway1475.8×0.020CASP8
TLR3-mediated TICAM1-dependent programmed cell death1475.8×0.020CASP8
Defective RIPK1-mediated regulated necrosis1475.8×0.020CASP8
Caspase activation via extrinsic apoptotic signalling pathway1356.9×0.020CASP8
Mitotic Telophase/Cytokinesis1356.9×0.020STAG2
TRAIL signaling1356.9×0.020CASP8
Epithelial-Mesenchymal Transition (EMT) during gastrulation1356.9×0.020FGFR1
FGFR1b ligand binding and activation1317.2×0.020FGFR1
TRIF-mediated programmed cell death1317.2×0.020CASP8
Cohesin Loading onto Chromatin1285.5×0.020STAG2
Establishment of Sister Chromatid Cohesion1259.6×0.020STAG2
Regulation by c-FLIP1259.6×0.020CASP8
CASP8 activity is inhibited1259.6×0.020CASP8
Dimerization of procaspase-81259.6×0.020CASP8
Signaling by activated point mutants of FGFR11237.9×0.020FGFR1
Caspase-mediated cleavage of cytoskeletal proteins1237.9×0.020CASP8
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -101219.6×0.021CASP8
Caspase activation via Death Receptors in the presence of ligand1190.3×0.022CASP8
FGFR1c ligand binding and activation1190.3×0.022FGFR1
Regulated Necrosis1178.4×0.023CASP8
Phospholipase C-mediated cascade: FGFR11167.9×0.023FGFR1
Diseases of programmed cell death1158.6×0.023CASP8
Regulation of NF-kappa B signaling1158.6×0.023CASP8
Receptor-type tyrosine-protein phosphatases1142.8×0.023PTPRD

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
regulation of postsynaptic density assembly2443.5×9e-04FGFR1, PTPRD
vitamin D3 metabolic process12106.5×0.009FGFR1
positive regulation of mitotic cell cycle DNA replication12106.5×0.009FGFR1
positive regulation of parathyroid hormone secretion12106.5×0.009FGFR1
regulation of extrinsic apoptotic signaling pathway in absence of ligand12106.5×0.009FGFR1
regulation of phosphate transport11404.3×0.009FGFR1
fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development11404.3×0.009FGFR1
regulation of lateral mesodermal cell fate specification11404.3×0.009FGFR1
syncytiotrophoblast cell differentiation involved in labyrinthine layer development11404.3×0.009CASP8
trans-synaptic signaling by trans-synaptic complex11404.3×0.009PTPRD
ventricular zone neuroblast division11053.2×0.010FGFR1
negative regulation of fibroblast growth factor production11053.2×0.010FGFR1
positive regulation of phospholipase activity1842.6×0.010FGFR1
regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling1842.6×0.010FGFR1
diphosphate metabolic process1842.6×0.010FGFR1
chordate embryonic development1702.2×0.010FGFR1
response to anesthetic1702.2×0.010CASP8
positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway1702.2×0.010FGFR1
response to cobalt ion1601.9×0.010CASP8
establishment of mitotic sister chromatid cohesion1601.9×0.010STAG2
cementum mineralization1601.9×0.010FGFR1
angiogenesis231.2×0.010CASP8, FGFR1
cell surface receptor protein tyrosine phosphatase signaling pathway1526.6×0.010PTPRD
TRAIL-activated apoptotic signaling pathway1468.1×0.010CASP8
auditory receptor cell development1468.1×0.010FGFR1
paraxial mesoderm development1421.3×0.010FGFR1
lung-associated mesenchyme development1421.3×0.010FGFR1
presynaptic membrane assembly1421.3×0.010PTPRD
response to sodium phosphate1421.3×0.010FGFR1
outer ear morphogenesis1383.0×0.011FGFR1

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 2

Druggability breadth: 3 of 4 evidence-associated genes (75%) 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.

SymbolExample approved molecule
CASP8PRIMAQUINE PHOSPHATE
FGFR1PONATINIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
FGFR1934
CASP824
STAG200
PTPRD00

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
PRIMAQUINE PHOSPHATE4CASP8
PONATINIB4FGFR1
PEMIGATINIB4FGFR1
NINTEDANIB4FGFR1
FEDRATINIB4FGFR1
TIVOZANIB4FGFR1
LENVATINIB4FGFR1
AXITINIB4FGFR1
SORAFENIB4FGFR1
NICLOSAMIDE4FGFR1
INFIGRATINIB PHOSPHATE4FGFR1
INFIGRATINIB4FGFR1
REGORAFENIB4FGFR1
ENTRECTINIB4FGFR1
CABOZANTINIB4FGFR1
CAPIVASERTIB4FGFR1
VANDETANIB4FGFR1
NINTEDANIB ESYLATE4FGFR1
BRIGATINIB4FGFR1
ERDAFITINIB4FGFR1
UPADACITINIB4FGFR1
FUTIBATINIB4FGFR1
PAZOPANIB4FGFR1
SUNITINIB4FGFR1
DASATINIB4FGFR1
MIDOSTAURIN4FGFR1
LINIFANIB3FGFR1
SEMAXANIB3FGFR1
OLVEREMBATINIB3FGFR1
BRIVANIB ALANINATE3FGFR1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

SymbolAssaysType breakdown
FGFR11,465Binding:1428, Functional:24, ADMET:13
CASP8116Binding:106, Functional:10
PTPRD1Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
CASP83.4.22.61caspase-8
FGFR12.7.10.1receptor protein-tyrosine kinase
PTPRD3.1.3.48protein-tyrosine-phosphatase

Cohort genes with high screening signal

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

SymbolChEMBL assays
CASP8116
FGFR11,465

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

30 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.

CompoundMax phaseCohort target (bioactivity)
PRIMAQUINE PHOSPHATE4CASP8
PONATINIB4FGFR1
PEMIGATINIB4FGFR1
NINTEDANIB4FGFR1
FEDRATINIB4FGFR1
TIVOZANIB4FGFR1
LENVATINIB4FGFR1
AXITINIB4FGFR1
SORAFENIB4FGFR1
NICLOSAMIDE4FGFR1
INFIGRATINIB PHOSPHATE4FGFR1
INFIGRATINIB4FGFR1
REGORAFENIB4FGFR1
ENTRECTINIB4FGFR1
CABOZANTINIB4FGFR1
CAPIVASERTIB4FGFR1
VANDETANIB4FGFR1
NINTEDANIB ESYLATE4FGFR1
BRIGATINIB4FGFR1
ERDAFITINIB4FGFR1
UPADACITINIB4FGFR1
FUTIBATINIB4FGFR1
PAZOPANIB4FGFR1
SUNITINIB4FGFR1
DASATINIB4FGFR1
MIDOSTAURIN4FGFR1
LINIFANIB3FGFR1
SEMAXANIB3FGFR1
OLVEREMBATINIB3FGFR1
BRIVANIB ALANINATE3FGFR1

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)2CASP8, FGFR1
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug1PTPRD
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug1STAG2

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
STAG20—
PTPRD1—

Clinical trials & evidence

Clinical trials

Clinical trials: 14.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified8
PHASE23
PHASE31
PHASE1/PHASE21
EARLY_PHASE11

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05024253PHASE3COMPLETEDPerioperative Use of Tranexamic (TXA) in Bone Tumor Surgery Will Change in Blood Loss and Transfusion Requirements.
NCT01946529PHASE2ACTIVE_NOT_RECRUITINGTherapeutic Trial for Patients With Ewing Sarcoma Family of Tumor and Desmoplastic Small Round Cell Tumors
NCT05395741PHASE1/PHASE2ACTIVE_NOT_RECRUITINGRegorafenib in Patients With Refractory Primary Bone Tumors
NCT00516295PHASE2COMPLETEDVincristine Sulfate, Topotecan Hydrochloride, and Cyclophosphamide With or Without Bevacizumab in Treating Young Patients With Refractory or First Recurrent Extracranial Ewing Sarcoma
NCT05116800PHASE2WITHDRAWNPhase 2 Study of 9-ING-41 With Chemotherapy in Sarcoma
NCT01825902EARLY_PHASE1COMPLETED18F-FLT Positron Emission Tomography and Diffusion-Weighted Magnetic Resonance Imaging in Planning Surgery and Radiation Therapy and Measuring Response in Patients With Newly Diagnosed Ewing Sarcoma
NCT04845893Not specifiedRECRUITINGObservational Study on Skeletal Ewing’s Sarcoma
NCT05033288Not specifiedRECRUITINGComparing Carbon Ion Therapy, Surgery, and Proton Therapy for Management of Pelvic Sarcomas Involving the Bone
NCT06068075Not specifiedACTIVE_NOT_RECRUITINGLiquid Biopsy in Ewing Sarcoma and Osteosarcoma as a Prognostic And Response Diagnostic: LEOPARD
NCT06935864Not specifiedRECRUITINGTissue Expression of Krüppel-Like Factors 4 and 7 in Bone Tumors
NCT00618813Not specifiedCOMPLETEDTwo Regimens of Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed Localized Ewing Sarcoma Family of Tumors
NCT00674193Not specifiedCOMPLETEDEvaluating Dactinomycin and Vincristine in Young Patients With Cancer
NCT01795430Not specifiedWITHDRAWNWhole-Body Radiation Therapy, Systemic Chemotherapy, and High-Dose Chemotherapy Followed By Stem Cell Rescue in Treating Patients With Poor-Risk Ewing Sarcoma
NCT03968471Not specifiedCOMPLETEDChemotherapy-induced Necrosis in Ewing Sarcoma

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
SODIUM CHLORIDE41
TOPOTECAN HYDROCHLORIDE41
ELRAGLUSIB21

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 4 predictive associations from 4 curated evidence items; also 3 diagnostic, 1 prognostic.

Molecular subtypeTherapyEffectLevelCIViC
PTPRD V253ICixutumumab + TeprotumumabSensitivity/ResponseCIViC CEID1856
CASP8 OverexpressionConatumumabSensitivity/ResponseCIViC DEID831
FGFR1 AmplificationPonatinibSensitivity/ResponseCIViC DEID1247
FGFR1 N546KPonatinibSensitivity/ResponseCIViC EEID1246

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

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This page pulls from 74 datasets indexed by BioBTree:

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