Pleuropulmonary blastoma

Summary

Pleuropulmonary blastoma (MONDO:0011014) is a disease caused by DICER1 (GenCC Strong), with 1 cohort gene and 10 clinical trials. Top therapeutic interventions include dexrazoxane, dactinomycin, and ifosfamide.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: DICER1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 167
• Clinical trials: 10

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 1 000 000	0.5	Europe	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	pleuropulmonary blastoma
Mondo ID	MONDO:0011014
EFO	EFO:0009052
MeSH	C537516
OMIM	601200
Orphanet	64742
DOID	DOID:4769
NCIT	C5669
SNOMED CT	707670009
UMLS	C1266144
MedGen	266105
GARD	0008757
Is cancer (heuristic)	no

Also known as: childhood pulmonary blastoma · paediatric pulmonary blastoma · pediatric pulmonary blastoma · pleuropulmonary blastoma · pleuropulmonary blastoma (morphologic abnormality) · PPB · PPB familial tumour and dysplasia syndrome · pulmonary blastoma of childhood

Data availability: 167 ClinVar variants · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › blastoma › pulmonary blastoma › pleuropulmonary blastoma

Related subtypes (2): classic pulmonary blastoma, epithelial predominant pulmonary blastoma

Subtypes (4): fetal lung interstitial tumor, pleuropulmonary blastoma type 1, pleuropulmonary blastoma type 2, pleuropulmonary blastoma type 3

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

167 retrieved; paginated sample, class counts are floors:

63 uncertain significance, 26 benign/likely benign, 20 conflicting classifications of pathogenicity, 18 pathogenic, 17 likely benign, 12 likely pathogenic, 8 benign, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2039665	NM_177438.3(DICER1):c.5428del (p.Asp1810fs)	DICER1	Pathogenic	criteria provided, multiple submitters, no conflicts
242054	NM_177438.3(DICER1):c.2026C>T (p.Arg676Ter)	DICER1	Pathogenic	criteria provided, multiple submitters, no conflicts
254288	NM_177438.3(DICER1):c.1525C>T (p.Arg509Ter)	DICER1	Pathogenic	criteria provided, multiple submitters, no conflicts
254301	NM_177438.3(DICER1):c.1966C>T (p.Arg656Ter)	DICER1	Pathogenic	criteria provided, multiple submitters, no conflicts
254303	NM_177438.3(DICER1):c.2062C>T (p.Arg688Ter)	DICER1	Pathogenic	criteria provided, multiple submitters, no conflicts
254309	NM_177438.3(DICER1):c.2392dup (p.Thr798fs)	DICER1	Pathogenic	criteria provided, multiple submitters, no conflicts
254332	NM_177438.3(DICER1):c.4309_4312del (p.Asp1437fs)	DICER1	Pathogenic	criteria provided, multiple submitters, no conflicts
254349	NM_177438.3(DICER1):c.5394del (p.Glu1799fs)	DICER1	Pathogenic	criteria provided, multiple submitters, no conflicts
30562	NM_177438.3(DICER1):c.5477C>A (p.Ser1826Ter)	DICER1	Pathogenic	criteria provided, single submitter
3602641	NM_177438.3(DICER1):c.3579_3594dup (p.Gly1199fs)	DICER1	Pathogenic	criteria provided, single submitter
3893094	NM_177438.3(DICER1):c.5446dup (p.Ala1816fs)	DICER1	Pathogenic	criteria provided, multiple submitters, no conflicts
3893095	NM_177438.3(DICER1):c.2518_2519del (p.Leu840fs)	DICER1	Pathogenic	criteria provided, multiple submitters, no conflicts
412077	NM_177438.3(DICER1):c.3007C>T (p.Arg1003Ter)	DICER1	Pathogenic	criteria provided, multiple submitters, no conflicts
429122	NM_177438.3(DICER1):c.4458dup (p.Ser1487fs)	DICER1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4469	NM_177438.3(DICER1):c.1507G>T (p.Glu503Ter)	DICER1	Pathogenic	criteria provided, multiple submitters, no conflicts
4470	NM_177438.3(DICER1):c.2830C>T (p.Arg944Ter)	DICER1	Pathogenic	criteria provided, multiple submitters, no conflicts
4472	NM_177438.3(DICER1):c.1630C>T (p.Arg544Ter)	DICER1	Pathogenic	criteria provided, multiple submitters, no conflicts
477107	NM_177438.3(DICER1):c.256del (p.Arg86fs)	DICER1	Pathogenic	criteria provided, multiple submitters, no conflicts
574777	NM_177438.3(DICER1):c.904-1G>C	DICER1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
690469	NM_177438.3(DICER1):c.2988-2A>G	DICER1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
933062	NM_177438.3(DICER1):c.2773G>T (p.Glu925Ter)	DICER1	Pathogenic	criteria provided, multiple submitters, no conflicts
1709651	NM_177438.3(DICER1):c.906dup (p.Leu303fs)	DICER1	Likely pathogenic	criteria provided, single submitter
1713278	NM_177438.3(DICER1):c.5365-4A>G	DICER1	Likely pathogenic	reviewed by expert panel
1791218	NM_177438.3(DICER1):c.2436+1dup	DICER1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2020385	NM_177438.3(DICER1):c.3093+1G>A	DICER1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2692308	NM_177438.3(DICER1):c.4849del (p.Leu1617fs)	DICER1	Likely pathogenic	criteria provided, single submitter
3065493	NM_177438.3(DICER1):c.5494dup (p.Gln1832fs)	DICER1	Likely pathogenic	criteria provided, single submitter
3068295	NM_177438.3(DICER1):c.1330G>T (p.Gly444Ter)	DICER1	Likely pathogenic	criteria provided, single submitter
3384157	NM_177438.3(DICER1):c.2468G>T (p.Gly823Val)	DICER1	Likely pathogenic	criteria provided, single submitter
3901186	NM_177438.3(DICER1):c.3525dup (p.Asn1176Ter)	DICER1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 7 · 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
DICER1	Strong	Autosomal dominant	pleuropulmonary blastoma	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DICER1	Orphanet:276399	Familial multinodular goiter
DICER1	Orphanet:284343	DICER1 tumor-predisposition syndrome
DICER1	Orphanet:404476	Global developmental delay-lung cysts-overgrowth-Wilms tumor syndrome
DICER1	Orphanet:99757	Embryonal rhabdomyosarcoma
DICER1	Orphanet:99914	Gynandroblastoma
DICER1	Orphanet:99915	Malignant granulosa cell tumor of the ovary
DICER1	Orphanet:99916	Malignant Sertoli-Leydig cell tumor of the ovary

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DICER1	HGNC:17098	ENSG00000100697	Q9UPY3	Endoribonuclease Dicer	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DICER1	Endoribonuclease Dicer	Double-stranded RNA (dsRNA) endoribonuclease playing a central role in short dsRNA-mediated post-transcriptional gene silencing.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DICER1	Enzyme (other)	yes	3.1.26.3	RNase_III_dom, Helicase_C-like, PAZ_dom

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
caput epididymis	1
cauda epididymis	1
tongue squamous epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DICER1	295	ubiquitous	marker	cauda epididymis, caput epididymis, tongue squamous epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DICER1	8,268

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DICER1	Q9UPY3	21

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
tRNA-derived small RNA (tsRNA or tRNA-related fragment, tRF) biogenesis	1	3806.7×	0.001	DICER1
Small interfering RNA (siRNA) biogenesis	1	1142.0×	0.002	DICER1
Regulation of MITF-M-dependent genes involved in apoptosis	1	634.4×	0.003	DICER1
MicroRNA (miRNA) biogenesis	1	456.8×	0.003	DICER1
M-decay: degradation of maternal mRNAs by maternally stored factors	1	326.3×	0.003	DICER1

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 term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of Schwann cell differentiation	1	8426.0×	0.001	DICER1
peripheral nervous system myelin formation	1	5617.3×	0.001	DICER1
global gene silencing by mRNA cleavage	1	5617.3×	0.001	DICER1
tRNA decay	1	3370.4×	0.001	DICER1
negative regulation of Schwann cell proliferation	1	2407.4×	0.001	DICER1
siRNA processing	1	1872.4×	0.002	DICER1
RISC complex assembly	1	1532.0×	0.002	DICER1
miRNA metabolic process	1	1404.3×	0.002	DICER1
apoptotic DNA fragmentation	1	1203.7×	0.002	DICER1
pre-miRNA processing	1	1123.5×	0.002	DICER1
miRNA processing	1	1053.2×	0.002	DICER1
nerve development	1	936.2×	0.002	DICER1
positive regulation of myelination	1	766.0×	0.002	DICER1
negative regulation of tumor necrosis factor-mediated signaling pathway	1	455.5×	0.003	DICER1
neuron projection morphogenesis	1	276.3×	0.004	DICER1
negative regulation of tumor necrosis factor production	1	251.5×	0.004	DICER1
negative regulation of gene expression	1	69.1×	0.015	DICER1
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	DICER1

Therapeutics

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

Symbol	Molecules	Max phase
DICER1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
DICER1	8	Binding:8

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DICER1	3.1.26.3	ribonuclease III

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).

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	1	DICER1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
DICER1	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 10.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	8
PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06647953	PHASE3	RECRUITING	Testing a Standardized Approach to Surgery and Chemotherapy for Type I Pleuropulmonary Blastoma or the Addition of an Anti-cancer Drug, Topotecan, to the Usual Treatment for Types II and III Pleuropulmonary Blastoma
NCT02452554	PHASE2	COMPLETED	Lorvotuzumab Mertansine in Treating Younger Patients With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor, or Synovial Sarcoma
NCT01247597	Not specified	RECRUITING	DICER1-related Pleuropulmonary Blastoma Cancer Predisposition Syndrome: A Natural History Study
NCT01464606	Not specified	ACTIVE_NOT_RECRUITING	International Pleuropulmonary Blastoma (PPB) Treatment and Biology Registry
NCT03382158	Not specified	RECRUITING	International PPB/DICER1 Registry
NCT07072143	Not specified	RECRUITING	An International Study on Pediatric Patients With Rare Tumors.
NCT00565903	Not specified	COMPLETED	Elucidating the Genetic Basis of the Pleuropulmonary Blastoma (PPB) Familial Cancer Syndrome
NCT01353300	Not specified	COMPLETED	Gene Mutation in Samples From Young Patients With Pleuropulmonary Blastoma Syndrome at Risk for Developing Cancer
NCT03044769	Not specified	UNKNOWN	Congenital Lung Anomalies (CLA) Swiss Database
NCT03044834	Not specified	COMPLETED	Review of the Paediatric Pleuropulmonary Blastoma French Series

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DEXRAZOXANE	4	3
DACTINOMYCIN	4	2
IFOSFAMIDE	4	2
TOPOTECAN	4	1
LORVOTUZUMAB MERTANSINE	2	1
CHEMBL4748391	0	2