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Atlas / Disease / Bone giant cell tumor

Bone giant cell tumor

disease
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Also known as benign bone giant cell tumorbenign bone giant cell tumourGCT of bonegiant cell tumor of bonegiant cell tumor of bone (morphologic abnormality)giant cell tumor of bone NOS (morphologic abnormality)giant cell tumor of the bonegiant cell tumor, benigngiant cell tumour of bone (morphologic abnormality)giant cell tumour of bone NOS (morphologic abnormality)giant cell tumour of the boneOsteoclastoma, benign

Summary

Bone giant cell tumor (MONDO:0005674) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver) and 21 clinical trials. Top therapeutic interventions include denosumab, dasatinib anhydrous, and indocyanine green acid form.

At a glance

  • Classification: Cancer
  • Prevalence: Unknown (Worldwide) [Orphanet-validated]
  • Cohort genes: 1
  • Clinical trials: 21

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

TypeClassValueGeographyValidation
Annual incidence1-9 / 1 000 0000.1404WorldwideValidated

Identifiers

Disease identifiers

FieldValue
Canonical namebone giant cell tumor
Mondo IDMONDO:0005674
EFOEFO:0007176
MeSHD018212
Orphanet363976
DOIDDOID:4305
NCITC121932
SNOMED CT697970009
UMLSC0206638
MedGen64624
GARD0013046
Is cancer (heuristic)yes

Also known as: benign bone giant cell tumor · benign bone giant cell tumour · GCT of bone · giant cell tumor of bone · giant cell tumor of bone (morphologic abnormality) · giant cell tumor of bone NOS (morphologic abnormality) · giant cell tumor of the bone · giant cell tumor, benign · giant cell tumour of bone (morphologic abnormality) · giant cell tumour of bone NOS (morphologic abnormality) · giant cell tumour of the bone · Osteoclastoma, benign

Data availability: 1 HPO phenotype · 21 cell lines.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › musculoskeletal system cancer › bone cancer › bone sarcoma › bone giant cell tumor

Related subtypes (12): undifferentiated pleomorphic sarcoma, bone angiosarcoma, undifferentiated high grade pleomorphic sarcoma of bone, bone fibrosarcoma, bone leiomyosarcoma, Ewing sarcoma of bone, bone osteosarcoma, liposarcoma of bone, periosteal chondrosarcoma, clear cell chondrosarcoma, dedifferentiated chondrosarcoma, malignancy in giant cell tumor of bone

Subtypes (1): giant cell reparative granuloma

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

Somatic driver evidence (intOGen + CIViC, cohort fanout)

GeneintOGen roleCancer typesCIViC
H3-3AActHGGNOS,PASTCIViC #2537

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

SubsetGenes
civic_only1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
H3-3AHGNC:4764ENSG00000163041P84243Histone H3.3civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
H3-3AHistone H3.3Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes.

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.

FamilyGenesFoldFDR
Other/Unknown11.8×0.558

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
H3-3AOther/UnknownnoHistone_H3/CENP-A, H2A/H2B/H3, Histone-fold

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)

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

Top tissues across cohort

TissueCohort genes
ganglionic eminence1
monocyte1
ventricular zone1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
H3-3A134ubiquitousmarkerganglionic eminence, monocyte, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
H3-3A1,595

Structural data

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

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
H3-3AP84243103

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 39. 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.

PathwayCohort genesFoldFDRSample cohort genes
Replacement of protamines by nucleosomes in the male pronucleus1271.9×0.012H3-3A
RNA Polymerase I Promoter Opening1184.2×0.012H3-3A
DNA methylation1178.4×0.012H3-3A
FXIIa activates plasma kallikrein-kinin system1173.0×0.012H3-3A
SIRT1 negatively regulates rRNA expression1170.4×0.012H3-3A
Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK31167.9×0.012H3-3A
Inhibition of DNA recombination at telomere1167.9×0.012H3-3A
Assembly of the ORC complex at the origin of replication1165.5×0.012H3-3A
Chromatin modifications during the maternal to zygotic transition (MZT)1163.1×0.012H3-3A
Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex1163.1×0.012H3-3A
Condensation of Prophase Chromosomes1156.4×0.012H3-3A
Defective pyroptosis1156.4×0.012H3-3A
PRC2 methylates histones and DNA1152.3×0.012H3-3A
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression1152.3×0.012H3-3A
CHD6, CHD7, CHD8, CHD9 subfamily1148.3×0.012H3-3A
Transcriptional regulation by small RNAs1144.6×0.012H3-3A
NuRD complex assembly1141.0×0.012H3-3A
Meiotic recombination1129.8×0.012H3-3A
Interaction of NuRD complexes with transcription factors1126.9×0.012H3-3A
Transcriptional regulation of granulopoiesis1125.5×0.012H3-3A
Pre-NOTCH Transcription and Translation1122.8×0.012H3-3A
B-WICH complex positively regulates rRNA expression1121.5×0.012H3-3A
RNA Polymerase I Promoter Escape1121.5×0.012H3-3A
Formation of the beta-catenin:TCF transactivating complex1120.2×0.012H3-3A
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function1120.2×0.012H3-3A
Negative Regulation of CDH1 Gene Transcription1120.2×0.012H3-3A
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)1117.7×0.012H3-3A
Regulation of PD-L1(CD274) transcription1108.8×0.012H3-3A
CHD1 and CHD2 subfamily1108.8×0.012H3-3A
Regulation of endogenous retroelements by KRAB-ZFP proteins1106.7×0.012H3-3A

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 termCohort genesFoldFDRSample cohort genes
negative regulation of chromosome condensation14213.0×0.002H3-3A
pericentric heterochromatin formation13370.4×0.002H3-3A
subtelomeric heterochromatin formation11532.0×0.003H3-3A
muscle cell differentiation1842.6×0.004H3-3A
telomere organization1624.1×0.004H3-3A
oocyte maturation1601.9×0.004H3-3A
nucleus organization1561.7×0.004H3-3A
embryo implantation1351.1×0.006H3-3A
single fertilization1183.2×0.008H3-3A
positive regulation of cell growth1183.2×0.008H3-3A
male gonad development1156.0×0.008H3-3A
spermatid development1145.3×0.008H3-3A
nucleosome assembly1140.4×0.008H3-3A
multicellular organism growth1137.0×0.008H3-3A
osteoblast differentiation1121.2×0.009H3-3A
cell population proliferation1102.8×0.010H3-3A

Therapeutics

Drugs indicated or in trials for this disease

1 approved drug — disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugStatus
DenosumabApproved (phase 4)

1 drug in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

DrugHighest phase
CalciumPhase 2

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

SymbolMoleculesMax phase
H3-3A00

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

SymbolAssaysType breakdown
H3-3A6Binding:6

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):

TierDefinitionGenesSymbols
AApproved (phase 4 drug)0
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug1H3-3A

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
H3-3A6—

Clinical trials & evidence

Clinical trials

Clinical trials: 21.

Phase distribution (across all retrieved trials)

PhaseTrials
PHASE27
Not specified6
PHASE43
PHASE33
PHASE1/PHASE22

Top trials by phase / activity

NCTPhaseStatusTitle
NCT04586660PHASE4ACTIVE_NOT_RECRUITINGStudy of XGEVA® (Denosumab) in Chinese Adults and Skeletally Mature Adolescents With Giant Cell Tumor of the Bone
NCT07315828PHASE4RECRUITINGAccuracy of Indocyanine Green (ICG) Fluorescence Imaging in Giant Cell Tumor of Bone Surgery
NCT03301857PHASE4COMPLETEDLong-term Safety Follow-up of Subjects With Giant Cell Tumor of Bone Treated With Denosumab in Study 20062004
NCT03295981PHASE3RECRUITINGLocal Bisphosphonate Effect on Recurrence Rate in Extremity Giant Cell Tumor of Bone
NCT05813665PHASE3NOT_YET_RECRUITINGA Study to Evaluate the Efficacy and Safety of Narlumosbart (JMT103) in Patients With Giant Cell Tumor of Bone
NCT03259152PHASE3UNKNOWNCharacteristics and Mechanism of Denosumab-treated Giant Cell Tumor of Bone
NCT03449108PHASE2ACTIVE_NOT_RECRUITINGLN-145 or LN-145-S1 in Treating Patients With Relapsed or Refractory Ovarian Cancer, Triple Negative Breast Cancer (TNBC), Anaplastic Thyroid Cancer, Osteosarcoma, or Other Bone and Soft Tissue Sarcomas
NCT05595603PHASE2RECRUITINGZoledronic Acid-loaded Bone Cement as a Local Adjuvant Therapy for Giant Cell Bone Tumor After Intralesional Curettage
NCT06647901PHASE1/PHASE2RECRUITINGEfficacy of ICG-based NIR Imaging in Intralesional Curettage of Giant Cell Tumors of Bone in Limbs: a Prospective, Single-center, Single-arm, Open Study
NCT00396279PHASE2COMPLETEDSafety and Efficacy Study of Denosumab in Patients With Recurrent or Unresectable Giant Cell Tumor of Bone
NCT00464620PHASE2COMPLETEDTrial of Dasatinib in Advanced Sarcomas
NCT00680992PHASE2COMPLETEDStudy of Denosumab in Subjects With Giant Cell Tumor of Bone
NCT00889590PHASE2TERMINATEDAdjuvant Zoledronic Acid in High Risk Giant Cell Tumour of Bone (GCT)
NCT03620149PHASE2TERMINATEDReduced Dose-density of Denosumab for Unresectable GCTB
NCT04255576PHASE1/PHASE2UNKNOWNEfficacy and Safety of JMT103 in Patients With Giant Cell Tumor of Bone
NCT07227961Not specifiedRECRUITINGPROMIS and Mobility Evaluation in Sarcoma Patients
NCT07609277Not specifiedRECRUITINGTRACP-5b for Diagnosis and Follow-up of Giant Cell Tumor of Bone
NCT02996734Not specifiedCOMPLETEDGiant Cell Tumor of the Extremities Treated With Surgery and/or Medical Treatment
NCT03358212Not specifiedUNKNOWNSafety and Efficacy of Post-operative Denosumab Strategy for Giant Cell Tumor of Bone Treatment in China
NCT04002817Not specifiedCOMPLETEDGiant Cell Tumor of the Bone in Young Patients
NCT05402865Not specifiedCOMPLETEDA Real-world Study on Patients of Unresectable Giant Cell Tumor of Bone

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
DENOSUMAB48
DASATINIB ANHYDROUS42
INDOCYANINE GREEN ACID FORM42
CALCIUM41
GENTAMICIN41
LIFILEUCEL41
NARLUMOSBART31
CHEMBL507282601
CHEMBL458319601
CHEMBL19589201
CHEMBL303959701
GENTAMICIN C1A01
GENTAMICIN C201

About this page

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

Generated
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This page pulls from 70 datasets indexed by BioBTree:

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