Rhabdomyosarcoma

Summary

Rhabdomyosarcoma (MONDO:0005212) is a disease (an umbrella term covering 20 Mondo subtypes) with 22 cohort genes and 149 clinical trials. The dominant Reactome pathway is Diseases of DNA repair (6 cohort genes). Molecularly, FGFR4 N535K confers sensitivity to FGF/VEGF Receptor Tyrosine Kinase Inhibitor + PD173074 in Rhabdomyosarcoma (CIViC Level D); 3 further subtype–drug associations are mapped below. Top therapeutic interventions include cyclophosphamide anhydrous, dactinomycin, and irinotecan.

At a glance

• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Umbrella term: 20 Mondo subtypes
• Cohort genes: 22
• ClinVar variants: 45
• Clinical trials: 149
• Precision-medicine evidence (CIViC): 4 subtype–drug associations

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 1 000 000	0.59	Europe	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	rhabdomyosarcoma
Mondo ID	MONDO:0005212
EFO	EFO:0002918
MeSH	D012208
Orphanet	780
DOID	DOID:3247
NCIT	C3359
SNOMED CT	302847003
UMLS	C0035412
MedGen	20561
GARD	0011951
MedDRA	10039022
Is cancer (heuristic)	no

Also known as: rhabdomyosarcoma · rhabdomyosarcoma (disease) · rhabdomyosarcoma, malignant

Data availability: 45 ClinVar variants · 8 GenCC gene-disease records · 1 HPO phenotype · 22 cell lines · 3 intOGen driver records.

Disease family

An umbrella term covering 20 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › sarcoma › soft tissue sarcoma › rhabdomyosarcoma

Related subtypes (45): esophagus sarcoma, bladder sarcoma, penile sarcoma, trachea sarcoma, retroperitoneal sarcoma, paranasal sinus sarcoma, pancreas sarcoma, vagina sarcoma, undifferentiated pleomorphic sarcoma, central nervous system sarcoma, ovarian sarcoma, liver sarcoma, lung sarcoma, laryngeal sarcoma, breast sarcoma, extraosseous osteosarcoma, rhabdoid tumor, mediastinum sarcoma, prostate sarcoma, gallbladder sarcoma, testis sarcoma, anus sarcoma, clear cell sarcoma, kidney sarcoma, thyroid sarcoma, heart sarcoma, small intestinal sarcoma, leiomyosarcoma, liposarcoma, fibrosarcoma, vulva sarcoma, intimal sarcoma, skin sarcoma, myxosarcoma, synovial sarcoma, alveolar soft part sarcoma, extraskeletal myxoid chondrosarcoma, angiosarcoma, epithelioid sarcoma, extraskeletal Ewing sarcoma, SMARCA4-deficient sarcoma of thorax, myxofibrosarcoma, desmoplastic small round cell tumor, undifferentiated round cell sarcoma, stromal sarcoma

Subtypes (20): orbit rhabdomyosarcoma, spindle cell rhabdomyosarcoma, liver rhabdomyosarcoma, central nervous system rhabdomyosarcoma, mediastinum rhabdomyosarcoma, rectum rhabdomyosarcoma, gallbladder rhabdomyosarcoma, ovary rhabdomyosarcoma, breast rhabdomyosarcoma, testis rhabdomyosarcoma, rhabdomyosarcoma with mixed embryonal and alveolar features, prostate rhabdomyosarcoma, embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma, vaginal rhabdomyosarcoma, uterine corpus rhabdomyosarcoma, rhabdomyosarcoma of the cervix uteri, pleomorphic rhabdomyosarcoma, oral rhabdomyosarcoma, rhabdomyosarcoma, embryonal, 2

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

45 retrieved; paginated sample, class counts are floors:

29 pathogenic, 9 pathogenic/likely pathogenic, 2 conflicting classifications of pathogenicity, 2 uncertain significance, 2 likely pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
37644	NM_007294.4(BRCA1):c.5177_5180del (p.Arg1726fs)	BRCA1	Pathogenic	reviewed by expert panel
55735	NM_007294.4(BRCA1):c.844_850dup (p.Gln284fs)	BRCA1	Pathogenic	reviewed by expert panel
37859	NM_000059.4(BRCA2):c.3847_3848del (p.Val1283fs)	BRCA2	Pathogenic	reviewed by expert panel
38085	NM_000059.4(BRCA2):c.7133C>G (p.Ser2378Ter)	BRCA2	Pathogenic	reviewed by expert panel
38122	NM_000059.4(BRCA2):c.7857G>A (p.Trp2619Ter)	BRCA2	Pathogenic	reviewed by expert panel
51400	NM_000059.4(BRCA2):c.3103G>T (p.Glu1035Ter)	BRCA2	Pathogenic	reviewed by expert panel
51493	NM_000059.4(BRCA2):c.3599_3600del (p.Asp1199_Cys1200insTer)	BRCA2	Pathogenic	reviewed by expert panel
51684	NM_000059.4(BRCA2):c.462_463del (p.Arg155_Asp156insTer)	BRCA2	Pathogenic	reviewed by expert panel
242054	NM_177438.3(DICER1):c.2026C>T (p.Arg676Ter)	DICER1	Pathogenic	criteria provided, multiple submitters, no conflicts
429141	NM_177438.3(DICER1):c.1174C>T (p.Arg392Ter)	DICER1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12602	NM_005343.4(HRAS):c.34G>A (p.Gly12Ser)	HRAS	Pathogenic	reviewed by expert panel
12603	NM_005343.4(HRAS):c.35G>C (p.Gly12Ala)	HRAS	Pathogenic	criteria provided, multiple submitters, no conflicts
90554	NM_000251.3(MSH2):c.1147C>T (p.Arg383Ter)	MSH2	Pathogenic	reviewed by expert panel
141058	NM_000179.3(MSH6):c.2300C>T (p.Thr767Ile)	MSH6	Pathogenic	reviewed by expert panel
185354	NM_001042492.3(NF1):c.5609G>A (p.Arg1870Gln)	NF1	Pathogenic	criteria provided, multiple submitters, no conflicts
188280	NM_001042492.3(NF1):c.2041C>T (p.Arg681Ter)	NF1	Pathogenic	criteria provided, multiple submitters, no conflicts
220715	NM_001042492.3(NF1):c.7153AACTTT[1] (p.2385NF[1])	NF1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
228381	NM_001042492.3(NF1):c.5305C>T (p.Arg1769Ter)	NF1	Pathogenic	criteria provided, multiple submitters, no conflicts
237556	NM_001042492.3(NF1):c.3826C>T (p.Arg1276Ter)	NF1	Pathogenic	criteria provided, multiple submitters, no conflicts
354	NM_001042492.3(NF1):c.1466A>G (p.Tyr489Cys)	NF1	Pathogenic	criteria provided, multiple submitters, no conflicts
547680	NM_001042492.3(NF1):c.6704+1G>T	NF1	Pathogenic	criteria provided, multiple submitters, no conflicts
573015	NM_001042492.3(NF1):c.4985G>A (p.Trp1662Ter)	NF1	Pathogenic	criteria provided, multiple submitters, no conflicts
978806	NM_001042492.3(NF1):c.3520C>T (p.Gln1174Ter)	NF1	Pathogenic	criteria provided, multiple submitters, no conflicts
9237	NM_000535.7(PMS2):c.2404C>T (p.Arg802Ter)	PMS2	Pathogenic	reviewed by expert panel
7819	NM_000314.8(PTEN):c.388C>T (p.Arg130Ter)	PTEN	Pathogenic	criteria provided, multiple submitters, no conflicts
422382	NM_004168.4(SDHA):c.2T>G (p.Met1Arg)	SDHA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
978229	NM_003001.5(SDHC):c.386G>A (p.Trp129Ter)	SDHC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12356	NM_000546.6(TP53):c.743G>A (p.Arg248Gln)	TP53	Pathogenic	reviewed by expert panel
12366	NM_000546.6(TP53):c.818G>A (p.Arg273His)	TP53	Pathogenic	reviewed by expert panel
12369	NM_000546.6(TP53):c.451C>A (p.Pro151Thr)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 104 · Orphanet: 132 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
BUB1B	Moderate	Autosomal recessive	rhabdomyosarcoma	8
CDKN1C	Moderate	Autosomal dominant	rhabdomyosarcoma	12
HRAS	Moderate	Autosomal dominant	rhabdomyosarcoma	8
MLH1	Moderate	Autosomal recessive	rhabdomyosarcoma	19
MSH2	Moderate	Autosomal recessive	rhabdomyosarcoma	17
MSH6	Moderate	Autosomal recessive	rhabdomyosarcoma	17
NBN	Moderate	Autosomal recessive	rhabdomyosarcoma	8
PMS2	Moderate	Autosomal recessive	rhabdomyosarcoma	15

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TP53	Orphanet:1333	Familial pancreatic carcinoma
TP53	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
TP53	Orphanet:1501	Adrenocortical carcinoma
TP53	Orphanet:210159	Adult hepatocellular carcinoma
TP53	Orphanet:251576	Gliosarcoma
TP53	Orphanet:251579	Giant cell glioblastoma
TP53	Orphanet:251899	Choroid plexus carcinoma
TP53	Orphanet:2807	Papilloma of choroid plexus
TP53	Orphanet:293199	Pleomorphic rhabdomyosarcoma
TP53	Orphanet:3318	Essential thrombocythemia
TP53	Orphanet:524	Li-Fraumeni syndrome
TP53	Orphanet:52688	Myelodysplastic syndrome
TP53	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
TP53	Orphanet:668	Osteosarcoma
TP53	Orphanet:67038	B-cell chronic lymphocytic leukemia
TP53	Orphanet:70573	Small cell lung cancer
TP53	Orphanet:96253	Cushing disease
TP53	Orphanet:99756	Alveolar rhabdomyosarcoma
TP53	Orphanet:99757	Embryonal rhabdomyosarcoma
HRAS	Orphanet:146	Differentiated thyroid carcinoma
HRAS	Orphanet:2612	Linear nevus sebaceus syndrome
HRAS	Orphanet:2874	Phakomatosis pigmentokeratotica
HRAS	Orphanet:3071	Costello syndrome
HRAS	Orphanet:79414	Woolly hair nevus
MSH2	Orphanet:144	Lynch syndrome
MSH2	Orphanet:252202	Constitutional mismatch repair deficiency syndrome
MSH6	Orphanet:144	Lynch syndrome
MSH6	Orphanet:252202	Constitutional mismatch repair deficiency syndrome
PMS2	Orphanet:144	Lynch syndrome
PMS2	Orphanet:252202	Constitutional mismatch repair deficiency syndrome
BUB1B	Orphanet:1052	Mosaic variegated aneuploidy syndrome
CDKN1C	Orphanet:231120	Beckwith-Wiedemann syndrome due to CDKN1C mutation
CDKN1C	Orphanet:397590	Silver-Russell syndrome due to a point mutation
CDKN1C	Orphanet:436144	Intrauterine growth restriction-short stature-early adult-onset diabetes syndrome
CDKN1C	Orphanet:85173	IMAGe syndrome
IL6	Orphanet:85414	Systemic-onset juvenile idiopathic arthritis
MLH1	Orphanet:144	Lynch syndrome
MLH1	Orphanet:252202	Constitutional mismatch repair deficiency syndrome
MYOD1	Orphanet:994	Fetal akinesia deformation sequence
NBN	Orphanet:1331	Familial prostate cancer
NBN	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
NBN	Orphanet:647	Nijmegen breakage syndrome
PDGFRA	Orphanet:168940	Chronic eosinophilic leukemia
PDGFRA	Orphanet:168947	Myeloid/lymphoid neoplasm associated with PDGFRA rearrangement
PDGFRA	Orphanet:199306	Cleft lip/palate
PDGFRA	Orphanet:314950	Primary hypereosinophilic syndrome
PDGFRA	Orphanet:44890	Gastrointestinal stromal tumor
PDGFRA	Orphanet:585877	B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormality
SDHA	Orphanet:139411	Carney triad

Cohort genes → proteins

22 cohort genes, 22 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	3
multi_evidence	19

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar,civic_evidence
HRAS	HGNC:5173	ENSG00000174775	P01112	GTPase HRas	gencc,clinvar
MSH2	HGNC:7325	ENSG00000095002	P43246	DNA mismatch repair protein Msh2	gencc,clinvar
MSH6	HGNC:7329	ENSG00000116062	P52701	DNA mismatch repair protein Msh6	gencc,clinvar
PMS2	HGNC:9122	ENSG00000122512	P54278	Mismatch repair endonuclease PMS2	gencc,clinvar
BUB1B	HGNC:1149	ENSG00000156970	O60566	Mitotic checkpoint serine/threonine-protein kinase BUB1 beta	gencc
CDKN1C	HGNC:1786	ENSG00000129757	P49918	Cyclin-dependent kinase inhibitor 1C	gencc
IL6	HGNC:6018	ENSG00000136244	P05231	Interleukin-6	civic_evidence
MLH1	HGNC:7127	ENSG00000076242	P40692	DNA mismatch repair protein Mlh1	gencc
MYOD1	HGNC:7611	ENSG00000129152	P15172	Myoblast determination protein 1	civic_evidence
NBN	HGNC:7652	ENSG00000104320	O60934	Nibrin	gencc
PDGFRA	HGNC:8803	ENSG00000134853	P16234	Platelet-derived growth factor receptor alpha	civic_evidence
SDHA	HGNC:10680	ENSG00000073578	P31040	Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial	clinvar
SDHC	HGNC:10682	ENSG00000143252	Q99643	Succinate dehydrogenase cytochrome b560 subunit, mitochondrial	clinvar
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	clinvar
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	clinvar
CBL	HGNC:1541	ENSG00000110395	P22681	E3 ubiquitin-protein ligase CBL	clinvar
DICER1	HGNC:17098	ENSG00000100697	Q9UPY3	Endoribonuclease Dicer	clinvar
ALK	HGNC:427	ENSG00000171094	Q9UM73	ALK tyrosine kinase receptor	clinvar
NF1	HGNC:7765	ENSG00000196712	P21359	Neurofibromin	clinvar
PTCH1	HGNC:9585	ENSG00000185920	Q13635	Protein patched homolog 1	clinvar
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
HRAS	GTPase HRas	Involved in the activation of Ras protein signal transduction.
MSH2	DNA mismatch repair protein Msh2	Component of the post-replicative DNA mismatch repair system (MMR).
MSH6	DNA mismatch repair protein Msh6	Component of the post-replicative DNA mismatch repair system (MMR).
PMS2	Mismatch repair endonuclease PMS2	Component of the post-replicative DNA mismatch repair system (MMR).
BUB1B	Mitotic checkpoint serine/threonine-protein kinase BUB1 beta	Essential component of the mitotic checkpoint.
CDKN1C	Cyclin-dependent kinase inhibitor 1C	Potent tight-binding inhibitor of several G1 cyclin/CDK complexes (cyclin E-CDK2, cyclin D2-CDK4, and cyclin A-CDK2) and, to lesser extent, of the mitotic cyclin B-CDC2.
IL6	Interleukin-6	Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism.
MLH1	DNA mismatch repair protein Mlh1	Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR).
MYOD1	Myoblast determination protein 1	Acts as a transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation.
NBN	Nibrin	Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis.
PDGFRA	Platelet-derived growth factor receptor alpha	Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis.
SDHA	Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial	Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
SDHC	Succinate dehydrogenase cytochrome b560 subunit, mitochondrial	Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
BRCA1	Breast cancer type 1 susceptibility protein	E3 ubiquitin-protein ligase that specifically mediates the formation of ‘Lys-6’-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
CBL	E3 ubiquitin-protein ligase CBL	E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors.
DICER1	Endoribonuclease Dicer	Double-stranded RNA (dsRNA) endoribonuclease playing a central role in short dsRNA-mediated post-transcriptional gene silencing.
ALK	ALK tyrosine kinase receptor	Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system.
NF1	Neurofibromin	Stimulates the GTPase activity of Ras.
PTCH1	Protein patched homolog 1	Acts as a receptor for sonic hedgehog (SHH), indian hedgehog (IHH) and desert hedgehog (DHH).
PTEN	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins.

Protein-family classification

Druggable: 7 · Difficult: 4 · Unknown: 11 · Druggable fraction: 0.32

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	3	3.8×	0.216
Phosphatase	1	3.8×	0.346
Enzyme (other)	3	1.6×	0.346
Transcription factor	4	1.5×	0.346
Other/Unknown	11	0.9×	0.778

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
HRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
MSH2	Other/Unknown	no		DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N, DNA_mismatch_repair_MutS_core
MSH6	Other/Unknown	no		PWWP_dom, DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N
PMS2	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr
BUB1B	Kinase	yes	2.7.11.1	Kinase-like_dom_sf, Mad3/Bub1_I, Bub1/Mad3
CDKN1C	Other/Unknown	no		CDI_dom, CDI_dom_sf
IL6	Other/Unknown	no		IL-6-like, 4_helix_cytokine-like_core, IL6/GCSF/MGF_CS
MLH1	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr
MYOD1	Transcription factor	no		MyoD_N, bHLH_dom, Myf5
NBN	Other/Unknown	no		FHA_dom, BRCT_dom, SMAD_FHA_dom_sf
PDGFRA	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
SDHA	Other/Unknown	no		FRD_SDH_FAD_BS, FAD-dep_OxRdtase_2_FAD-bd, Succ_DH_flav_su_fwd
SDHC	Enzyme (other)	yes	1.3.5.1	SuccDH_FuR_B_TM-su, Succ_DH_cytb556, Succ_DH_cyt_bsu_CS
BRCA1	Transcription factor	no	2.3.2.27	BRCT_dom, Znf_RING, BRCA1
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
CBL	Transcription factor	no	2.3.2.27	Znf_RING, Adaptor_Cbl_N_hlx, UBA-like_sf
DICER1	Enzyme (other)	yes	3.1.26.3	RNase_III_dom, Helicase_C-like, PAZ_dom
ALK	Kinase	yes	2.7.10.1	Prot_kinase_dom, MAM_dom, Ser-Thr/Tyr_kinase_cat_dom
NF1	Other/Unknown	no		CRAL-TRIO_dom, RasGAP_dom, Rho_GTPase_activation_prot
PTCH1	Other/Unknown	no		SSD, TM_rcpt_patched, HMGCR/SNAP/NPC1-like_SSD
PTEN	Phosphatase	yes	3.1.3.16	Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom

Expression context

Cohort genes with no expression data: 0.

21 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)	22
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	6
male germ line stem cell (sensu Vertebrata) in testis	5
secondary oocyte	3
ganglionic eminence	2
oocyte	2
adrenal tissue	2
cauda epididymis	2
tibia	2
primordial germ cell in gonad	2
trigeminal ganglion	2
sperm	2
calcaneal tendon	2
tendon of biceps brachii	1
skin of abdomen	1
skin of leg	1
zone of skin	1
embryo	1
prefrontal cortex	1
thymus	1
C1 segment of cervical spinal cord	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
HRAS	139	ubiquitous	marker	skin of abdomen, skin of leg, zone of skin
MSH2	278	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone
MSH6	293	ubiquitous	marker	ventricular zone, embryo, ganglionic eminence
PMS2	143	ubiquitous	marker	thymus, prefrontal cortex, male germ line stem cell (sensu Vertebrata) in testis
BUB1B	210	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone
CDKN1C	134	ubiquitous	marker	placenta, adrenal tissue, C1 segment of cervical spinal cord
IL6	200	ubiquitous	marker	cartilage tissue, vena cava, gall bladder
MLH1	296	ubiquitous	marker	tibialis anterior, skeletal muscle tissue of rectus abdominis, deltoid
MYOD1	51	tissue_specific	yes	triceps brachii, skeletal muscle tissue of biceps brachii, gluteal muscle
NBN	299	ubiquitous	marker	endometrium epithelium, mammary duct, cauda epididymis
PDGFRA	289	ubiquitous	marker	tibia, decidua, synovial joint
SDHA	143	ubiquitous	marker	apex of heart, heart left ventricle, mucosa of transverse colon
SDHC	134	ubiquitous	marker	islet of Langerhans, right adrenal gland cortex, right adrenal gland
BRCA1	208	ubiquitous	marker	ventricular zone, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
CBL	271	ubiquitous	marker	primordial germ cell in gonad, trigeminal ganglion, male germ line stem cell (sensu Vertebrata) in testis
DICER1	295	ubiquitous	marker	cauda epididymis, caput epididymis, tongue squamous epithelium
ALK	181	broad	marker	sperm, male germ cell, male germ line stem cell (sensu Vertebrata) in testis
NF1	283	ubiquitous	marker	colonic epithelium, calcaneal tendon, adrenal tissue
PTCH1	275	ubiquitous	marker	tibia, dorsal root ganglion, trigeminal ganglion
PTEN	256	ubiquitous	marker	sperm, endothelial cell, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 32.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
PTEN	11,626
IL6	9,239
BRCA1	9,064
DICER1	8,268
HRAS	8,064
SDHA	6,141
NF1	5,540
SDHC	5,278
PDGFRA	5,186

Intra-cohort edges

A	B	Sources
BRCA1	BRCA2	string_interaction
BRCA1	MLH1	string_interaction
BRCA1	MSH2	string_interaction
BRCA1	MSH6	string_interaction
BRCA1	NBN	string_interaction
BRCA1	NF1	string_interaction
BRCA1	PMS2	string_interaction
BRCA1	TP53	string_interaction
BRCA2	MLH1	string_interaction
BRCA2	MSH2	string_interaction
BRCA2	MSH6	string_interaction
BRCA2	NBN	string_interaction
BRCA2	PMS2	string_interaction
BRCA2	TP53	string_interaction
HRAS	MSH6	intact
HRAS	NF1	intact
HRAS	TP53	string_interaction
MLH1	MSH2	string_interaction
MLH1	MSH6	string_interaction
MLH1	NBN	string_interaction
MLH1	PMS2	biogrid_interaction, intact, string_interaction
MSH2	MSH6	biogrid_interaction, intact, string_interaction
MSH2	PMS2	string_interaction
MSH6	NBN	string_interaction
MSH6	PMS2	string_interaction
NF1	PDGFRA	string_interaction
NF1	PTEN	biogrid_interaction, string_interaction
NF1	TP53	string_interaction
PDGFRA	PTEN	string_interaction
PDGFRA	SDHC	string_interaction
PTEN	TP53	string_interaction
SDHA	SDHC	biogrid_interaction, string_interaction

Structural data

PDB: 20 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TP53	P04637	313
HRAS	P01112	246
ALK	Q9UM73	79
BRCA1	P38398	33
CBL	P22681	33
MSH2	P43246	30
NF1	P21359	26
DICER1	Q9UPY3	21
IL6	P05231	17
PTCH1	Q13635	16
PDGFRA	P16234	15
BRCA2	P51587	14
PTEN	P60484	12
PMS2	P54278	9
BUB1B	O60566	9
MSH6	P52701	8
MLH1	P40692	7
NBN	O60934	7
SDHA	P31040	5
SDHC	Q99643	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CDKN1C	P49918	63.93
MYOD1	P15172	62.04

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 322. Enrichment computed across 22 evidence-associated genes (22 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 22 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Diseases of DNA repair	6	155.7×	3e-10	MSH2, MSH6, BRCA1, BRCA2, MLH1, NBN
Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)	4	148.3×	2e-06	MSH2, MSH6, PMS2, MLH1
Mismatch Repair	3	389.3×	2e-06	MSH2, MSH6, MLH1
Diseases of Mismatch Repair (MMR)	3	389.3×	2e-06	MSH2, MSH6, MLH1
DNA Repair	6	26.9×	4e-06	MSH2, MSH6, BRCA1, BRCA2, MLH1, NBN
TP53 Regulates Transcription of DNA Repair Genes	5	41.2×	6e-06	TP53, MSH2, PMS2, BRCA1, MLH1
Meiosis	4	51.9×	4e-05	BRCA1, BRCA2, MLH1, NBN
Defective homologous recombination repair (HRR) due to PALB2 loss of function	3	129.8×	5e-05	BRCA1, BRCA2, NBN
Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)	3	111.2×	6e-05	MSH2, PMS2, MLH1
Diseases of DNA Double-Strand Break Repair	3	111.2×	6e-05	BRCA1, BRCA2, NBN
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	3	111.2×	6e-05	BRCA1, BRCA2, NBN
Disease	10	6.0×	6e-05	MSH2, MSH6, BRCA1, BRCA2, CBL, CDKN1C, ALK, MLH1 (+2 more)
Defective Mismatch Repair Associated With MLH1	2	519.1×	8e-05	PMS2, MLH1
Defective Mismatch Repair Associated With MSH6	2	519.1×	8e-05	MSH2, MSH6
Defective Mismatch Repair Associated With PMS2	2	519.1×	8e-05	PMS2, MLH1
Resolution of D-Loop Structures	3	86.5×	9e-05	BRCA1, BRCA2, NBN
Reproduction	4	34.6×	9e-05	BRCA1, BRCA2, MLH1, NBN
Defective Mismatch Repair Associated With MSH2	2	346.1×	2e-04	MSH2, MSH6
Impaired BRCA2 binding to PALB2	3	62.3×	2e-04	BRCA1, BRCA2, NBN
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	3	57.7×	3e-04	BRCA1, BRCA2, NBN
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	3	57.7×	3e-04	BRCA1, BRCA2, NBN
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	3	57.7×	3e-04	BRCA1, BRCA2, NBN
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	3	53.7×	3e-04	BRCA1, BRCA2, NBN
Meiotic recombination	4	23.6×	3e-04	BRCA1, BRCA2, MLH1, NBN
Cell Cycle	6	9.8×	3e-04	BRCA1, BRCA2, BUB1B, CDKN1C, MLH1, NBN
Homologous DNA Pairing and Strand Exchange	3	51.9×	3e-04	BRCA1, BRCA2, NBN
Homology Directed Repair	3	42.1×	5e-04	BRCA1, BRCA2, NBN
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	3	42.1×	5e-04	BRCA1, BRCA2, NBN
Impaired BRCA2 binding to RAD51	3	42.1×	5e-04	BRCA1, BRCA2, NBN
Resolution of D-loop Structures through Holliday Junction Intermediates	3	41.0×	5e-04	BRCA1, BRCA2, NBN

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 22 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
somatic recombination of immunoglobulin gene segments	3	574.5×	2e-06	MSH2, MSH6, PMS2
somatic hypermutation of immunoglobulin genes	4	191.5×	2e-06	MSH2, MSH6, PMS2, MLH1
isotype switching	4	153.2×	2e-06	MSH2, MSH6, MLH1, NBN
positive regulation of isotype switching to IgA isotypes	3	383.0×	5e-06	MSH2, PMS2, MLH1
mismatch repair	4	117.8×	5e-06	MSH2, MSH6, PMS2, MLH1
double-strand break repair	5	46.1×	7e-06	TP53, MSH2, BRCA1, BRCA2, NBN
positive regulation of isotype switching to IgG isotypes	3	208.9×	3e-05	MSH2, PMS2, MLH1
intrinsic apoptotic signaling pathway	4	65.2×	3e-05	TP53, HRAS, MSH6, NBN
response to X-ray	3	121.0×	1e-04	TP53, MSH2, BRCA2
negative regulation of stem cell proliferation	3	114.9×	1e-04	TP53, NF1, PTCH1
adrenal gland development	3	91.9×	2e-04	CDKN1C, NF1, PDGFRA
response to gamma radiation	3	79.2×	4e-04	TP53, BRCA2, CBL
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	3	67.6×	5e-04	TP53, MSH2, BRCA2
mitochondrial electron transport, succinate to ubiquinone	2	306.4×	7e-04	SDHA, SDHC
determination of adult lifespan	3	58.9×	7e-04	TP53, MSH2, MSH6
cellular response to ionizing radiation	3	56.0×	8e-04	TP53, BRCA1, BRCA2
fibroblast proliferation	3	53.4×	8e-04	TP53, HRAS, NF1
neuroblast proliferation	3	50.0×	1e-03	TP53, NBN, NF1
DNA damage response, signal transduction by p53 class mediator	3	48.9×	1e-03	TP53, BRCA2, NBN
negative regulation of Schwann cell proliferation	2	218.9×	0.001	DICER1, NF1
intrinsic apoptotic signaling pathway in response to DNA damage	3	44.2×	0.001	MSH6, BRCA1, MLH1
DNA strand resection involved in replication fork processing	2	191.5×	0.001	BRCA1, NBN
stem cell proliferation	3	42.6×	0.001	TP53, NF1, PTCH1
cellular senescence	3	40.3×	0.001	TP53, HRAS, BRCA2
DNA damage tolerance	2	153.2×	0.002	MSH2, BRCA1
homologous recombination	2	127.7×	0.002	BRCA1, NBN
forebrain morphogenesis	2	127.7×	0.002	NF1, PTEN
negative regulation of neuroblast proliferation	2	109.4×	0.003	TP53, NF1
negative regulation of DNA recombination	2	102.1×	0.003	MSH2, MSH6
regulation of DNA damage checkpoint	2	102.1×	0.003	BRCA1, BRCA2

Therapeutics

Drugs indicated for this disease

0 approved, 5 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Dactinomycin	Phase 3 (in late-stage trials)
Etoposide	Phase 3 (in late-stage trials)
Filgrastim	Phase 3 (in late-stage trials)
Ifosfamide	Phase 3 (in late-stage trials)
Sargramostim	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Bevacizumab, Dexrazoxane, Doxorubicin, Etoposide Phosphate, Irinotecan, Methionine, Sorafenib, Temozolomide, Temsirolimus, Tirapazamine, Topotecan, Vincristine, Vinorelbine.

Drug target analysis

Approved (phase 4): 8 · Phase ≥3: 8 · Phased (≥1): 9 · Undrugged: 13

Druggability breadth: 16 of 22 evidence-associated genes (73%) 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
TP53	NITROFURANTOIN
HRAS	LONAFARNIB
BUB1B	CERITINIB
IL6	PREDNISOLONE
PDGFRA	PONATINIB
SDHA	LINEZOLID
BRCA1	RIBOFLAVIN
ALK	CERITINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
PDGFRA	77	4
ALK	61	4
BRCA1	12	4
HRAS	4	4
IL6	3	4
MSH6	1	2
BUB1B	1	4
SDHA	1	4
MSH2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 9.

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

Symbol	Assays	Type breakdown
ALK	1,815	Binding:1801, Functional:13, ADMET:1
PDGFRA	1,172	Binding:1160, Functional:8, ADMET:4
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
HRAS	48	Binding:45, Functional:3
IL6	16	Binding:16
BRCA1	13	Binding:9, Functional:4
BUB1B	12	Binding:12
MSH6	10	Binding:10
MSH2	9	Binding:9
DICER1	8	Binding:8
PTEN	8	Binding:8
CBL	4	Binding:2, Toxicity:2
PTCH1	4	Binding:4
SDHA	3	Binding:3
NBN	2	Binding:2
PMS2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HRAS	3.6.5.2	small monomeric GTPase
BUB1B	2.7.11.1	non-specific serine/threonine protein kinase
PDGFRA	2.7.10.1	receptor protein-tyrosine kinase
SDHC	1.3.5.1	succinate dehydrogenase
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase
CBL	2.3.2.27	RING-type E3 ubiquitin transferase
DICER1	3.1.26.3	ribonuclease III
ALK	2.7.10.1	receptor protein-tyrosine kinase
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TP53	869
PDGFRA	1,172
ALK	1,815

Pharmacogenomics

Cohort genes with a PharmGKB record: 22; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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)
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	8	TP53, HRAS, BUB1B, IL6, PDGFRA, SDHA, BRCA1, ALK
B	Phased (≥1) drug, not yet approved	1	MSH6
C	Druggable family + PDB, no drug	3	SDHC, DICER1, PTEN
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	10	MSH2, PMS2, CDKN1C, MLH1, MYOD1, NBN, BRCA2, CBL, NF1, PTCH1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PMS2	1	MSH6
MLH1	0	MSH6
NBN	2	BRCA1
SDHC	0	SDHA
BRCA2	0	BRCA1
PTEN	8	TP53
MSH2	9	—
CDKN1C	0	—
MYOD1	0	—
CBL	4	—
DICER1	8	—
NF1	0	—
PTCH1	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 149.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	47
PHASE1	43
PHASE1/PHASE2	26
Not specified	23
PHASE3	6
PHASE4	2
EARLY_PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00339118	PHASE4	UNKNOWN	EpSSG (European Soft Tissue Sarcoma Study Group) Protocol for Non-Metastatic Rhabdomyosarcoma in Children
NCT04854018	PHASE4	COMPLETED	Indo-cyanine Green (ICG) in Paediatric Oncology MIS
NCT02567435	PHASE3	ACTIVE_NOT_RECRUITING	Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma
NCT04994132	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Compare Early Use of Vinorelbine and Maintenance Therapy for Patients With High Risk Rhabdomyosarcoma
NCT06836492	PHASE3	RECRUITING	A Prospective Clinical Cohort Study on Stratified Treatment of Rhabdomyosarcoma Based on Risk Factors.
NCT07466316	PHASE3	NOT_YET_RECRUITING	A Study Comparing Higher Dose Chemotherapy Over a Shorter Amount of Time to Lower Dose Chemotherapy Plus Maintenance Over a Longer Amount of Time in Patients With Newly Diagnosed Intermediate-Risk Rhabdomyosarcoma (IR RMS)
NCT00162695	PHASE3	TERMINATED	Rhabdomyosarcoma and Malignant Soft Tissue Tumours of Childhood
NCT00354835	PHASE3	COMPLETED	Combination Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Rhabdomyosarcoma
NCT00186992	PHASE2	ACTIVE_NOT_RECRUITING	Radiation Therapy to Treat Musculoskeletal Tumors
NCT00840047	PHASE2	ACTIVE_NOT_RECRUITING	Methionine PET/CT Studies In Patients With Cancer
NCT01871766	PHASE2	ACTIVE_NOT_RECRUITING	Risk-Adapted Focal Proton Beam Radiation and/or Surgery in Patients With Low, Intermediate and High Risk Rhabdomyosarcoma Receiving Standard or Intensified Chemotherapy
NCT02867592	PHASE2	ACTIVE_NOT_RECRUITING	Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors
NCT03155620	PHASE2	ACTIVE_NOT_RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT03213652	PHASE2	ACTIVE_NOT_RECRUITING	Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
NCT03213704	PHASE2	ACTIVE_NOT_RECRUITING	Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)
NCT03698994	PHASE2	ACTIVE_NOT_RECRUITING	Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
NCT03709680	PHASE2	ACTIVE_NOT_RECRUITING	Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors
NCT04195555	PHASE2	ACTIVE_NOT_RECRUITING	Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)
NCT04284774	PHASE2	ACTIVE_NOT_RECRUITING	Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04320888	PHASE2	ACTIVE_NOT_RECRUITING	Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04388839	PHASE2	ACTIVE_NOT_RECRUITING	Evolutionary Therapy for Rhabdomyosarcoma
NCT04625907	PHASE1/PHASE2	RECRUITING	FaR-RMS: An Overarching Study for Children and Adults With Frontline and Relapsed RhabdoMyoSarcoma
NCT04796012	PHASE1/PHASE2	RECRUITING	VITAS: Atezolizumab in Combination With Chemotherapy for Pediatric Relapsed/Refractory Solid Tumors
NCT04901702	PHASE1/PHASE2	RECRUITING	Study of Onivyde With Talazoparib or Temozolomide in Children With Recurrent Solid Tumors and Ewing Sarcoma
NCT06023641	PHASE2	RECRUITING	Treatment of Newly Diagnosed Rhabdomyosarcoma Using Molecular Risk Stratification and Liposomal Irinotecan Based Therapy in Children With Intermediate and High Risk Disease
NCT06094101	PHASE1/PHASE2	RECRUITING	Personalized Vaccination in Fusion+ Sarcoma Patients (PerVision)
NCT06456892	PHASE1/PHASE2	RECRUITING	Effectiveness of Pucotenlimab Combined With Standard Chemotherapy Regimen
NCT06521567	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study of Cobolimab Plus Dostarlimab in Pediatric and Young Adult Participants With Cancer
NCT06541262	PHASE1/PHASE2	RECRUITING	Silmitasertib (CX-4945) in Combination With Chemotherapy for Relapsed Refractory Solid Tumors
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06683846	PHASE2	RECRUITING	Ivonescimab in the Treatment of Multiple Advanced Tumors
NCT06684327	PHASE2	RECRUITING	Multi-cohort, Single-arm Phase II Study of Albumin-paclitaxel, Ifosfamide, and Cisplatin in the Treatment of Rare Advanced Tumors
NCT06709495	PHASE1/PHASE2	RECRUITING	Phase 1/2 Trial to Evaluate the Safety and Efficacy of PEEL-224 in Combination With Vincristine and Temozolomide in Adolescents and Young Adults With Relapsed or Refractory Sarcomas
NCT06721689	PHASE1/PHASE2	RECRUITING	PEEL-224, Vincristine and Temozolomide in Pediatric Solid Tumors
NCT07137884	PHASE2	NOT_YET_RECRUITING	Anlotinib Hydrochloride Capsules in Maintenance Treatment for Intermediate-High Risk Rhabdomyosarcoma in Children
NCT07355855	PHASE2	NOT_YET_RECRUITING	A Clinical Study on the Efficacy and Safety of All-trans Retinoic Acid Combined With VAC Regimen in the Treatment of Intermediate-to-high-risk Rhabdomyosarcoma
NCT00001335	PHASE2	COMPLETED	New Therapeutic Strategies for Patients With Ewing’s Sarcoma Family of Tumors, High Risk Rhabdomyosarcoma, and Neuroblastoma
NCT00001564	PHASE2	COMPLETED	A Pilot Study of Tumor-Specific Peptide Vaccination and IL-2 With or Without Autologous T Cell Transplantation in Recurrent Pediatric Sarcomas
NCT00001566	PHASE2	COMPLETED	A Pilot Study of Autologous T-Cell Transplantation With Vaccine Driven Expansion of Anti-Tumor Effectors After Cytoreductive Therapy in Metastatic Pediatric Sarcomas
NCT00180947	PHASE2	UNKNOWN	Study of Vinorelbine and Cyclofosfamide Among Patients With Refractory Tumours or in Relapse

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CYCLOPHOSPHAMIDE ANHYDROUS	4	16
DACTINOMYCIN	4	9
IRINOTECAN	4	5
VINORELBINE	4	4
DEXRAZOXANE	4	3
DOXORUBICIN	4	3
DASATINIB ANHYDROUS	4	2
INDOCYANINE GREEN ACID FORM	4	2
EPIRUBICIN	4	1
ETOPOSIDE PHOSPHATE	4	1
FERUMOXYTOL	4	1
IFOSFAMIDE	4	1
IMETELSTAT SODIUM	4	1
INDINAVIR SULFATE	4	1
REGORAFENIB	4	1
SONIDEGIB	4	1
TEMSIROLIMUS	4	1
TOPOTECAN	4	1
VINCRISTINE	4	1
METHIONINE	3	1
RECOMBINANT HUMAN THROMBOPOIETIN	3	1
REGRAMOSTIM	3	1
CIXUTUMUMAB	2	2
ADAVOSERTIB	2	1
CD40 LIGAND	2	1
CHEMBL4748391	0	8
CHEMBL2369717	0	1
CHEMBL4583196	0	1
CHEMBL1234268	0	1
RACEMETHIONINE	-1	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 4 predictive associations from 4 curated evidence items; also 2 prognostic.

Molecular subtype	Therapy	Effect	Level	CIViC
FGFR4 N535K	FGF/VEGF Receptor Tyrosine Kinase Inhibitor + PD173074	Sensitivity/Response	CIViC D	EID8906
FGFR4 V550E	FGF/VEGF Receptor Tyrosine Kinase Inhibitor + PD173074	Sensitivity/Response	CIViC D	EID8907
PDGFRA Overexpression	Sunitinib	Sensitivity/Response	CIViC D	EID7988
IL6 Overexpression	Bazedoxifene	Resistance	CIViC D	EID7956