Spindle cell rhabdomyosarcoma

Summary

Spindle cell rhabdomyosarcoma (MONDO:0002581) is a disease with 2 cohort genes and 2 clinical trials. Molecularly, FUS::TFCP2 Fusion AND ALK Exon 2-18 Deletion confers sensitivity to Alectinib in Spindle Cell Rhabdomyosarcoma (CIViC Level C). Top therapeutic interventions include cyclophosphamide anhydrous, dactinomycin, and vinorelbine.

At a glance

• Cohort genes: 2
• Clinical trials: 2
• Precision-medicine evidence (CIViC): 1 subtype–drug association

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spindle cell rhabdomyosarcoma
Mondo ID	MONDO:0002581
DOID	DOID:3260
NCIT	C6519
SNOMED CT	404055006
UMLS	C1266134
MedGen	224766
GARD	0023175
Is cancer (heuristic)	no

Also known as: SCRMS · spindle cell rhabdomyosarcoma (morphologic abnormality)

Disease family

An umbrella term covering 3 Mondo subtypes.

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

Related subtypes (3): spindle cell synovial sarcoma, spindle cell liposarcoma, intimal sarcoma

Subtypes (3): intraosseous spindle cell rhabdomyosarcoma with TFCP2/NCOA2 rearrangements, congenital/infantile spindle cell rhabdomyosarcoma with VGLL2/NCOA2/CITED2 rearrangements, childhood spindle cell rhabdomyosarcoma

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ALK	Orphanet:146	Differentiated thyroid carcinoma
ALK	Orphanet:178342	Inflammatory myofibroblastic tumor
ALK	Orphanet:251877	Ganglioneuroblastoma
ALK	Orphanet:251992	Ganglioneuroma
ALK	Orphanet:300895	ALK-positive anaplastic large cell lymphoma
ALK	Orphanet:364043	ALK-positive large B-cell lymphoma
ALK	Orphanet:626	Large/giant congenital melanocytic nevus
ALK	Orphanet:635	Neuroblastoma
MYOD1	Orphanet:994	Fetal akinesia deformation sequence

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ALK	HGNC:427	ENSG00000171094	Q9UM73	ALK tyrosine kinase receptor	civic_evidence
MYOD1	HGNC:7611	ENSG00000129152	P15172	Myoblast determination protein 1	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
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.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5

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	1	13.9×	0.142
Transcription factor	1	4.1×	0.228

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ALK	Kinase	yes	2.7.10.1	Prot_kinase_dom, MAM_dom, Ser-Thr/Tyr_kinase_cat_dom
MYOD1	Transcription factor	no		MyoD_N, bHLH_dom, Myf5

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
sperm	1
gluteal muscle	1
skeletal muscle tissue of biceps brachii	1
triceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ALK	181	broad	marker	sperm, male germ cell, male germ line stem cell (sensu Vertebrata) in testis
MYOD1	51	tissue_specific	yes	triceps brachii, skeletal muscle tissue of biceps brachii, gluteal muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ALK	4,792
MYOD1	3,624

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ALK	Q9UM73	79

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MYOD1	P15172	62.04

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 23. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Drug resistance of ALK mutants	1	5710.0×	5e-04	ALK
ASP-3026-resistant ALK mutants	1	5710.0×	5e-04	ALK
NVP-TAE684-resistant ALK mutants	1	5710.0×	5e-04	ALK
alectinib-resistant ALK mutants	1	5710.0×	5e-04	ALK
brigatinib-resistant ALK mutants	1	5710.0×	5e-04	ALK
ceritinib-resistant ALK mutants	1	5710.0×	5e-04	ALK
crizotinib-resistant ALK mutants	1	5710.0×	5e-04	ALK
lorlatinib-resistant ALK mutants	1	5710.0×	5e-04	ALK
MDK and PTN in ALK signaling	1	1427.5×	0.002	ALK
ALK mutants bind TKIs	1	475.8×	0.005	ALK
Signaling by ALK	1	285.5×	0.007	ALK
TGFBR3 expression	1	228.4×	0.008	MYOD1
Myogenesis	1	190.3×	0.009	MYOD1
Signaling by TGFBR3	1	184.2×	0.009	MYOD1
Signaling by ALK in cancer	1	135.9×	0.011	ALK
Signal Transduction	2	10.2×	0.014	ALK, MYOD1
Signaling by ALK fusions and activated point mutants	1	75.1×	0.018	ALK
Signaling by TGFB family members	1	57.7×	0.022	MYOD1
CHD1 and CHD2 subfamily	1	54.4×	0.022	MYOD1
Diseases of signal transduction by growth factor receptors and second messengers	1	28.4×	0.040	ALK
Signaling by Receptor Tyrosine Kinases	1	25.8×	0.042	ALK
Developmental Biology	1	7.2×	0.140	MYOD1
Disease	1	6.5×	0.147	ALK

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
myoblast fate determination	1	4213.0×	0.002	MYOD1
response to environmental enrichment	1	4213.0×	0.002	ALK
negative regulation of myoblast proliferation	1	4213.0×	0.002	MYOD1
positive regulation of skeletal muscle tissue regeneration	1	2808.7×	0.002	MYOD1
skeletal muscle fiber adaptation	1	2808.7×	0.002	MYOD1
positive regulation of snRNA transcription by RNA polymerase II	1	2808.7×	0.002	MYOD1
regulation of dopamine receptor signaling pathway	1	2106.5×	0.002	ALK
cellular response to oxygen levels	1	2106.5×	0.002	MYOD1
myotube cell development	1	1685.2×	0.002	MYOD1
myotube differentiation involved in skeletal muscle regeneration	1	1685.2×	0.002	MYOD1
swimming behavior	1	1685.2×	0.002	ALK
muscle cell fate commitment	1	1404.3×	0.003	MYOD1
response to stress	1	1203.7×	0.003	ALK
positive regulation of skeletal muscle fiber development	1	1053.2×	0.003	MYOD1
peptidyl-tyrosine autophosphorylation	1	936.2×	0.003	ALK
phosphorylation	1	648.1×	0.004	ALK
positive regulation of muscle cell differentiation	1	561.7×	0.005	MYOD1
positive regulation of myoblast fusion	1	526.6×	0.005	MYOD1
positive regulation of dendrite development	1	495.6×	0.005	ALK
negative regulation of lipid catabolic process	1	421.3×	0.005	ALK
regulation of neuron differentiation	1	366.4×	0.006	ALK
cellular response to glucocorticoid stimulus	1	312.1×	0.007	MYOD1
myoblast fusion	1	300.9×	0.007	MYOD1
skeletal muscle fiber development	1	271.8×	0.007	MYOD1
adult behavior	1	234.1×	0.008	ALK
cellular response to estradiol stimulus	1	205.5×	0.009	MYOD1
positive regulation of myoblast differentiation	1	183.2×	0.009	MYOD1
skeletal muscle cell differentiation	1	172.0×	0.010	MYOD1
skeletal muscle tissue development	1	145.3×	0.011	MYOD1
energy homeostasis	1	135.9×	0.011	ALK

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
ALK	CERITINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ALK	61	4
MYOD1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CERITINIB	4	ALK
BOSUTINIB	4	ALK
CRIZOTINIB	4	ALK
ALECTINIB	4	ALK
ENTRECTINIB	4	ALK
LORLATINIB	4	ALK
GILTERITINIB	4	ALK
OSIMERTINIB	4	ALK
BRIGATINIB	4	ALK
REPOTRECTINIB	4	ALK
FEDRATINIB	4	ALK
RUXOLITINIB	4	ALK
INFIGRATINIB PHOSPHATE	4	ALK
INFIGRATINIB	4	ALK
PALBOCICLIB	4	ALK
VANDETANIB	4	ALK
UPADACITINIB	4	ALK
PAZOPANIB	4	ALK
NINTEDANIB	4	ALK
SUNITINIB	4	ALK
ERLOTINIB	4	ALK
MIDOSTAURIN	4	ALK
DACTOLISIB	3	ALK
LINIFANIB	3	ALK
SEMAXANIB	3	ALK
CANERTINIB	3	ALK
ROCILETINIB	3	ALK
ALVOCIDIB	3	ALK
CEDIRANIB	3	ALK
QUERCETIN	3	ALK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ALK	1,815	Binding:1801, Functional:13, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ALK	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ALK	1,815

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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)
CERITINIB	4	ALK
BOSUTINIB	4	ALK
CRIZOTINIB	4	ALK
ALECTINIB	4	ALK
ENTRECTINIB	4	ALK
LORLATINIB	4	ALK
GILTERITINIB	4	ALK
OSIMERTINIB	4	ALK
BRIGATINIB	4	ALK
REPOTRECTINIB	4	ALK
FEDRATINIB	4	ALK
RUXOLITINIB	4	ALK
INFIGRATINIB PHOSPHATE	4	ALK
INFIGRATINIB	4	ALK
PALBOCICLIB	4	ALK
VANDETANIB	4	ALK
UPADACITINIB	4	ALK
PAZOPANIB	4	ALK
NINTEDANIB	4	ALK
SUNITINIB	4	ALK
ERLOTINIB	4	ALK
MIDOSTAURIN	4	ALK
DACTOLISIB	3	ALK
LINIFANIB	3	ALK
SEMAXANIB	3	ALK
CANERTINIB	3	ALK
ROCILETINIB	3	ALK
ALVOCIDIB	3	ALK
CEDIRANIB	3	ALK
QUERCETIN	3	ALK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ALK
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	MYOD1

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)
MYOD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
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

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CYCLOPHOSPHAMIDE ANHYDROUS	4	2
DACTINOMYCIN	4	2
VINORELBINE	4	2
IRINOTECAN HYDROCHLORIDE	4	1
TEMSIROLIMUS	4	1
CHEMBL4748391	0	2
CHEMBL541887	0	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 1 predictive associations from 1 curated evidence items; also 18 diagnostic, 8 prognostic.

Molecular subtype	Therapy	Effect	Level	CIViC
FUS::TFCP2 Fusion AND ALK Exon 2-18 Deletion	Alectinib	Sensitivity/Response	CIViC C	EID12406