Desmoplastic/nodular medulloblastoma

Summary

Desmoplastic/nodular medulloblastoma (MONDO:0016711) is a disease with 2 cohort genes and 1 clinical trial. Molecularly, PARP6::NTRK3 Fusion confers sensitivity to Entrectinib in Desmoplastic/nodular Medulloblastoma (CIViC Level C). Top therapeutic interventions include cyclophosphamide anhydrous.

At a glance

• Prevalence: <1 / 1 000 000 (Europe) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 3
• Clinical trials: 1
• Precision-medicine evidence (CIViC): 1 subtype–drug association

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	<1 / 1 000 000	0.01	Europe	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	desmoplastic/nodular medulloblastoma
Mondo ID	MONDO:0016711
Orphanet	251863
NCIT	C4956
UMLS	C0751291
MedGen	148272
GARD	0017215
Is cancer (heuristic)	no

Also known as: Desmoplastic medulloblastoma · desmoplastic medulloblastoma · desmoplastic nodular medulloblastoma · desmoplastic/nodular medulloblastoma

Data availability: 3 ClinVar variants · 1 cell line.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › cerebellar disorder › cerebellar neoplasm › medulloblastoma › desmoplastic/nodular medulloblastoma

Related subtypes (13): brain stem medulloblastoma, large cell medulloblastoma, cerebellar vermis medulloblastoma, adult medulloblastoma, melanotic medulloblastoma, childhood medulloblastoma, medullomyoblastoma with myogenic differentiation, anaplastic/large cell medulloblastoma, medulloblastoma with extensive nodularity, classic medulloblastoma, medulloblastoma WNT activated, medulloblastoma SHH activated, medulloblastoma non-WNT/non-SHH

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

3 retrieved; paginated sample, class counts are floors:

3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1802698	NM_152641.4(ARID2):c.1837C>T (p.Gln613Ter)	ARID2	Pathogenic	criteria provided, single submitter
280869	NM_006565.4(CTCF):c.610dup (p.Thr204fs)	CTCF	Pathogenic	criteria provided, multiple submitters, no conflicts
3572	NC_000010.11:g.(102444036_?)_(?_104726221)del	LOC130004644	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CTCF	Orphanet:363611	CTCF-related neurodevelopmental disorder
ARID2	Orphanet:1465	Coffin-Siris syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CTCF	HGNC:13723	ENSG00000102974	P49711	Transcriptional repressor CTCF	clinvar
ARID2	HGNC:18037	ENSG00000189079	Q68CP9	AT-rich interactive domain-containing protein 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CTCF	Transcriptional repressor CTCF	Chromatin binding factor that binds to DNA sequence specific sites and regulates the 3D structure of chromatin.
ARID2	AT-rich interactive domain-containing protein 2	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 0 · 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
Transcription factor	2	8.3×	0.015

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CTCF	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Zinc_finger_PRDM4/PRDM1/PRDM14
ARID2	Transcription factor	no		ARID_dom, DNA-bd_RFX, Znf_C2H2_type

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
endometrium epithelium	1
ganglionic eminence	1
ventricular zone	1
pancreatic ductal cell	1
secondary oocyte	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CTCF	297	ubiquitous	marker	ventricular zone, ganglionic eminence, endometrium epithelium
ARID2	253	ubiquitous	marker	sperm, pancreatic ductal cell, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CTCF	5,713
ARID2	2,190

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CTCF	P49711	21
ARID2	Q68CP9	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. 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
Formation of the polybromo-BAF (pBAF) complex	1	317.2×	0.030	ARID2
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	150.3×	0.030	ARID2
CHD6, CHD7, CHD8, CHD9 subfamily	1	74.2×	0.030	CTCF
RMTs methylate histone arginines	1	73.2×	0.030	ARID2
Transcriptional regulation by RUNX1	1	73.2×	0.030	ARID2
Activation of anterior HOX genes in hindbrain development during early embryogenesis	1	45.7×	0.038	CTCF
Chromatin organization	1	40.8×	0.038	ARID2
Chromatin modifying enzymes	1	36.1×	0.038	ARID2
RNA Polymerase II Transcription	1	11.3×	0.106	ARID2
Gene expression (Transcription)	1	8.9×	0.120	ARID2
Generic Transcription Pathway	1	7.5×	0.128	ARID2

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
regulation of centromeric sister chromatid cohesion	1	2808.7×	0.009	CTCF
protein localization to chromosome, centromeric region	1	1053.2×	0.009	CTCF
coronary artery morphogenesis	1	936.2×	0.009	ARID2
homeostatic process	1	842.6×	0.009	ARID2
negative regulation of cell population proliferation	2	42.1×	0.009	CTCF, ARID2
chromatin looping	1	601.9×	0.009	CTCF
negative regulation of gene expression via chromosomal CpG island methylation	1	526.6×	0.009	CTCF
genomic imprinting	1	495.6×	0.009	CTCF
nucleosome disassembly	1	401.2×	0.009	ARID2
regulation of G0 to G1 transition	1	337.0×	0.009	ARID2
cardiac muscle cell development	1	312.1×	0.009	CTCF
regulation of nucleotide-excision repair	1	300.9×	0.009	ARID2
cardiac muscle cell proliferation	1	290.6×	0.009	ARID2
DNA methylation-dependent constitutive heterochromatin formation	1	271.8×	0.009	CTCF
regulation of mitotic metaphase/anaphase transition	1	247.8×	0.009	ARID2
embryonic organ development	1	240.7×	0.009	ARID2
positive regulation of T cell differentiation	1	227.7×	0.009	ARID2
epigenetic regulation of gene expression	1	191.5×	0.009	CTCF
positive regulation of double-strand break repair via homologous recombination	1	191.5×	0.009	ARID2
heart morphogenesis	1	187.2×	0.009	ARID2
positive regulation of myoblast differentiation	1	183.2×	0.009	ARID2
positive regulation of double-strand break repair	1	172.0×	0.010	ARID2
regulation of G1/S transition of mitotic cell cycle	1	153.2×	0.010	ARID2
positive regulation of cell differentiation	1	133.8×	0.011	ARID2
regulation of transcription by RNA polymerase II	2	11.7×	0.011	CTCF, ARID2
chromosome segregation	1	86.9×	0.016	CTCF
mitochondrion organization	1	75.9×	0.018	CTCF
negative regulation of cell migration	1	55.8×	0.023	ARID2
gene expression	1	39.9×	0.031	CTCF
chromatin remodeling	1	36.5×	0.032	ARID2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 2 of 2 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
CTCF	0	0
ARID2	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
ARID2	7	Binding:7
CTCF	2	Binding:2

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

0 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.

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	2	CTCF, ARID2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CTCF	2	—
ARID2	7	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02017964	PHASE2	COMPLETED	Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed, Non-metastatic Desmoplastic Medulloblastoma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CYCLOPHOSPHAMIDE ANHYDROUS	4	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 1 predictive associations from 1 curated evidence items.

Molecular subtype	Therapy	Effect	Level	CIViC
PARP6::NTRK3 Fusion	Entrectinib	Sensitivity/Response	CIViC C	EID12608