Wilms tumor (nephroblastoma) is the most common pediatric kidney malignancy, typically affecting children under 5 years of age. It exemplifies the concept of developmental cancer, arising from persistent embryonic renal blastemal cells that fail to undergo normal differentiation. Multiple genes are implicated including WT1, WTX (AMER1), and CTNNB1, which together regulate kidney development and Wnt signaling. Wilms tumor is one of the great successes of pediatric oncology, with cure rates exceeding 90% for favorable histology tumors through a combination of surgery, chemotherapy, and risk-adapted radiation. Anaplastic histology confers worse prognosis.
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name: Wilms Tumor
creation_date: '2026-01-26T02:55:13Z'
updated_date: '2026-04-13T05:05:42Z'
description: >-
Wilms tumor (nephroblastoma) is the most common pediatric kidney malignancy,
typically affecting children under 5 years of age. It exemplifies the concept
of developmental cancer, arising from persistent embryonic renal blastemal
cells that fail to undergo normal differentiation. Multiple genes are implicated
including WT1, WTX (AMER1), and CTNNB1, which together regulate kidney development
and Wnt signaling. Wilms tumor is one of the great successes of pediatric oncology,
with cure rates exceeding 90% for favorable histology tumors through a combination
of surgery, chemotherapy, and risk-adapted radiation. Anaplastic histology confers
worse prognosis.
categories:
- Pediatric Cancer
- Kidney Cancer
- Solid Tumor
parents:
- kidney neoplasm
has_subtypes:
- name: Favorable Histology
classification: anaplasia_status
display_name: Favorable Histology Wilms Tumor
description: >-
Approximately 90% of Wilms tumors have favorable histology without anaplasia.
These tumors have excellent outcomes with >90% overall survival using current
treatment protocols.
mappings:
ncit_mappings:
- term:
id: NCIT:C6951
label: Nonanaplastic Kidney Wilms Tumor
mapping_predicate: skos:closeMatch
mapping_source: NCIT
mapping_justification: NCIT nonanaplastic kidney Wilms tumor closely matches favorable histology Wilms tumor.
- name: Anaplastic
classification: anaplasia_status
display_name: Anaplastic Wilms Tumor
description: >-
Characterized by extreme nuclear enlargement and pleomorphism with atypical
mitoses. May be focal or diffuse. Diffuse anaplasia confers significantly
worse prognosis and requires treatment intensification.
mappings:
ncit_mappings:
- term:
id: NCIT:C6952
label: Anaplastic Kidney Wilms Tumor
mapping_predicate: skos:closeMatch
mapping_source: NCIT
mapping_justification: NCIT anaplastic kidney Wilms tumor closely matches the Wilms anaplastic subtype.
- name: Blastemal Predominant
classification: histological_pattern
display_name: Blastemal Predominant Wilms Tumor
description: >-
Blastemal-predominant Wilms tumor is a high-risk histologic pattern,
particularly after preoperative chemotherapy, and reflects persistence of
residual blastemal cells with relative chemotherapy resistance.
evidence:
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
High-risk histology includes blastemal-type tumors, as a predominance of
residual blastemal cells is a marker of chemotherapy resistance.
explanation: >-
Supports blastemal-predominant Wilms tumor as a distinct histologic
pattern with high-risk behavior.
mappings:
ncit_mappings:
- term:
id: NCIT:C9147
label: Blastema Predominant Kidney Wilms Tumor
mapping_predicate: skos:closeMatch
mapping_source: NCIT
mapping_justification: NCIT blastema-predominant kidney Wilms tumor closely matches this histologic subtype.
- name: Epithelial Predominant
classification: histological_pattern
display_name: Epithelial Predominant Wilms Tumor
description: >-
Epithelial-predominant Wilms tumor emphasizes tubule- and glomeruloid-like
differentiation and generally falls into a more favorable post-chemotherapy
histologic group.
evidence:
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Stromal and epithelia-type nephroblastoma show an excellent outcome after
preoperative chemotherapy
explanation: >-
Supports epithelial-predominant Wilms tumor as a recognized histologic
pattern with favorable outcomes after preoperative chemotherapy.
mappings:
ncit_mappings:
- term:
id: NCIT:C9146
label: Epithelial Predominant Kidney Wilms Tumor
mapping_predicate: skos:closeMatch
mapping_source: NCIT
mapping_justification: NCIT epithelial-predominant kidney Wilms tumor closely matches this histologic subtype.
- name: Stromal Predominant
classification: histological_pattern
display_name: Stromal Predominant Wilms Tumor
description: >-
Stromal-predominant Wilms tumor emphasizes mesenchymal differentiation and
is generally associated with favorable outcomes after preoperative
chemotherapy.
evidence:
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Stromal and epithelia-type nephroblastoma show an excellent outcome after
preoperative chemotherapy
explanation: >-
Supports stromal-predominant Wilms tumor as a recognized histologic
pattern with favorable post-chemotherapy outcomes.
mappings:
ncit_mappings:
- term:
id: NCIT:C9148
label: Stromal Predominant Kidney Wilms Tumor
mapping_predicate: skos:closeMatch
mapping_source: NCIT
mapping_justification: NCIT stromal-predominant kidney Wilms tumor closely matches this histologic subtype.
- name: Mixed Cell Type
classification: histological_pattern
display_name: Mixed Cell Type Wilms Tumor
description: >-
Mixed-cell-type Wilms tumor corresponds to the classic triphasic pattern
with blastemal, epithelial, and stromal components in variable
proportions.
evidence:
- reference: PMID:27512769
reference_title: "Wilms’ Tumour – Histology and Differential Diagnosis."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Typically, WT comprises three histological components namely blastemal,
epithelial and stromal. The proportion and the degree of maturation of these
components vary significantly, making the histological appearance of each tumour
unique.
explanation: >-
Supports mixed-cell-type Wilms tumor as the classic triphasic histologic
pattern with variable proportions of blastemal, epithelial, and stromal
elements.
mappings:
ncit_mappings:
- term:
id: NCIT:C9149
label: Mixed Cell Type Kidney Wilms Tumor
mapping_predicate: skos:closeMatch
mapping_source: NCIT
mapping_justification: NCIT mixed-cell-type kidney Wilms tumor closely matches the triphasic mixed-cell histologic subtype.
- name: Bilateral
classification: laterality
display_name: Bilateral Wilms Tumor
description: >-
Synchronous bilateral tumors occur in approximately 5-10% of cases and are
enriched for germline WT1 mutations and post-zygotic epigenetic
hypermethylation at 11p15.5. Treatment aims for nephron-sparing approaches
to preserve renal function.
evidence:
- reference: PMID:38110397
reference_title: "Genetic and epigenetic features of bilateral Wilms tumor predisposition in patients from the Children's Oncology Group AREN18B5-Q."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Developing synchronous bilateral Wilms tumor suggests an underlying
(epi)genetic predisposition.
explanation: >-
Confirms bilateral Wilms tumor is driven by underlying genetic and
epigenetic predisposition events, with WT1 germline variants in 14.8%
and 11p15.5 epigenetic changes as the predominant events.
- name: Unilateral
classification: laterality
display_name: Unilateral Wilms Tumor
description: >-
Most Wilms tumors present as unilateral renal masses involving a single
kidney at diagnosis.
- name: Hereditary Predisposition-Associated
classification: predisposition_context
display_name: Hereditary Predisposition-Associated Wilms Tumor
description: >-
A subset of Wilms tumors arises in the setting of germline or mosaic
predisposition, including WT1-associated syndromes and 11p15 epigenetic
dysregulation.
evidence:
- reference: PMID:37916284
reference_title: "Wilms' tumor gene 1: lessons from the interface between kidney development and cancer."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In 1990, mutations of the Wilms' tumor-1 gene (WT1), encoding a transcription
factor in the embryonic kidney, were found in 10-15% of Wilms' tumors; germline
WT1 mutations were associated with hereditary syndromes involving glomerular and
reproductive tract dysplasia.
explanation: >-
Supports a hereditary predisposition-associated Wilms tumor subgroup linked
to germline WT1 alterations and related syndromic presentations.
mappings:
ncit_mappings:
- term:
id: NCIT:C8496
label: Hereditary Kidney Wilms Tumor
mapping_predicate: skos:closeMatch
mapping_source: NCIT
mapping_justification: NCIT hereditary kidney Wilms tumor closely matches hereditary predisposition-associated Wilms tumor.
- name: Sporadic
classification: predisposition_context
display_name: Sporadic Wilms Tumor
description: >-
Most Wilms tumors arise sporadically without an identified germline
predisposition syndrome, although they still accumulate somatic and
epigenetic driver alterations.
- name: Childhood
classification: age_group
display_name: Childhood Wilms Tumor
subtype_term:
preferred_term: childhood kidney Wilms tumor
term:
id: MONDO:0024676
label: childhood kidney Wilms tumor
description: >-
The canonical presentation of Wilms tumor is in early childhood, most often
before 5 years of age.
mappings:
ncit_mappings:
- term:
id: NCIT:C27730
label: Childhood Kidney Wilms Tumor
mapping_predicate: skos:closeMatch
mapping_source: NCIT
mapping_justification: NCIT childhood kidney Wilms tumor closely matches the childhood age-group subtype.
- name: Adult
classification: age_group
display_name: Adult Wilms Tumor
description: >-
Adult Wilms tumor is rare and represents an uncommon age-defined clinical
presentation of nephroblastoma.
mappings:
ncit_mappings:
- term:
id: NCIT:C6180
label: Adult Kidney Wilms Tumor
mapping_predicate: skos:closeMatch
mapping_source: NCIT
mapping_justification: NCIT adult kidney Wilms tumor closely matches the adult age-group subtype.
disease_term:
preferred_term: Wilms tumor
term:
id: MONDO:0006058
label: Wilms tumor
pathophysiology:
- name: WT1 Inactivation
description: >-
WT1 is a transcription factor essential for normal kidney and gonad development.
Biallelic WT1 inactivation occurs in 10-15% of Wilms tumors. Germline WT1
mutations cause WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies,
intellectual disability) and Denys-Drash syndrome. WT1 functions at multiple
stages of kidney development, including the transition from resting stem cells
to committed nephron progenitor cells.
cell_types:
- preferred_term: metanephric mesenchyme stem cell
term:
id: CL:0000324
label: metanephric mesenchyme stem cell
gene:
preferred_term: WT1
modifier: DECREASED
term:
id: hgnc:12796
label: WT1
gene_products:
- preferred_term: WT1 protein
term:
id: NCIT:C17549
label: Wilms Tumor Protein
biological_processes:
- preferred_term: cell differentiation
modifier: DECREASED
term:
id: GO:0030154
label: cell differentiation
- preferred_term: metanephros development
modifier: ABNORMAL
term:
id: GO:0001656
label: metanephros development
locations:
- preferred_term: kidney
term:
id: UBERON:0002113
label: kidney
evidence:
- reference: PMID:37916284
reference_title: "Wilms' tumor gene 1: lessons from the interface between kidney development and cancer."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In 1990, mutations of the Wilms' tumor-1 gene (WT1), encoding a transcription
factor in the embryonic kidney, were found in 10-15% of Wilms' tumors; germline
WT1 mutations were associated with hereditary syndromes involving glomerular and
reproductive tract dysplasia.
explanation: >-
Confirms WT1 mutation frequency in Wilms tumors and association with
hereditary syndromes including WAGR and Denys-Drash.
- reference: PMID:37916284
reference_title: "Wilms' tumor gene 1: lessons from the interface between kidney development and cancer."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
WT1 functions at multiple stages of kidney development, including the transition
from resting stem cells to committed nephron progenitor, which it primes to
respond to WNT9b signals from the ureteric bud.
explanation: >-
Details the role of WT1 in kidney development and nephron progenitor
cell commitment.
downstream:
- target: Blocked Nephron Differentiation
description: WT1 loss prevents normal renal blastemal differentiation
- name: WTX (AMER1) Inactivation
description: >-
WTX (AMER1) is a component of the beta-catenin destruction complex and a
negative regulator of Wnt signaling. WTX inactivation occurs in approximately
15-20% of Wilms tumors and leads to constitutive Wnt pathway activation.
gene:
preferred_term: AMER1
modifier: DECREASED
term:
id: hgnc:26837
label: AMER1
gene_products:
- preferred_term: WTX protein
term:
id: NCIT:C68721
label: APC Membrane Recruitment Protein 1
biological_processes:
- preferred_term: Wnt signaling pathway
modifier: INCREASED
term:
id: GO:0016055
label: Wnt signaling pathway
evidence:
- reference: PMID:25018051
reference_title: "The development of Wilms tumor: from WT1 and microRNA to animal models."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This has been illustrated by the findings that mutations of Wnt/β-catenin
pathway-related WT1, β-catenin, and WTX together account for about one-third of
Wilms tumor cases.
explanation: >-
Confirms WTX as one of the key Wnt pathway genes mutated in Wilms tumor.
downstream:
- target: Canonical Wnt Signaling Hyperactivation
description: Loss of WTX stabilizes beta-catenin signaling in nephrogenic progenitors
- name: CTNNB1 Activating Mutation
description: >-
Activating mutations in CTNNB1 (beta-catenin) occur in approximately 15%
of Wilms tumors, affecting exon 3 to stabilize beta-catenin and activate
canonical Wnt signaling. CTNNB1 mutations are strongly associated with
WT1 mutations, promoting proliferation and blocking differentiation.
cell_types:
- preferred_term: nephrogenic zone cell
term:
id: CL:0009019
label: nephrogenic zone cell
gene:
preferred_term: CTNNB1
modifier: INCREASED
term:
id: hgnc:2514
label: CTNNB1
gene_products:
- preferred_term: beta-catenin
term:
id: NCIT:C17478
label: Catenin Beta-1
biological_processes:
- preferred_term: Wnt signaling pathway
modifier: INCREASED
term:
id: GO:0016055
label: Wnt signaling pathway
evidence:
- reference: PMID:25018051
reference_title: "The development of Wilms tumor: from WT1 and microRNA to animal models."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This has been illustrated by the findings that mutations of Wnt/β-catenin
pathway-related WT1, β-catenin, and WTX together account for about one-third of
Wilms tumor cases.
explanation: >-
Confirms CTNNB1 as one of the key Wnt pathway genes mutated in Wilms tumor.
downstream:
- target: Canonical Wnt Signaling Hyperactivation
description: Exon 3 mutations stabilize beta-catenin and drive constitutive Wnt output
- name: Canonical Wnt Signaling Hyperactivation
description: >-
Aberrant beta-catenin signaling downstream of AMER1 loss or CTNNB1 activation
sustains nephrogenic progenitors in a developmental state and cooperates with
WT1 loss in Wilms tumor initiation.
cell_types:
- preferred_term: nephrogenic zone cell
term:
id: CL:0009019
label: nephrogenic zone cell
biological_processes:
- preferred_term: Wnt signaling pathway
modifier: INCREASED
term:
id: GO:0016055
label: Wnt signaling pathway
- preferred_term: cell differentiation
modifier: DECREASED
term:
id: GO:0030154
label: cell differentiation
evidence:
- reference: PMID:25018051
reference_title: "The development of Wilms tumor: from WT1 and microRNA to animal models."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This has been illustrated by the findings that mutations of Wnt/β-catenin
pathway-related WT1, β-catenin, and WTX together account for about one-third of
Wilms tumor cases.
explanation: >-
Supports canonical Wnt signaling as a major convergent Wilms tumor mechanism
downstream of AMER1 and CTNNB1 lesions.
downstream:
- target: Blocked Nephron Differentiation
description: Constitutive beta-catenin signaling prevents normal nephron maturation
- target: Persistent Blastemal Progenitor State
description: Wnt output maintains embryonal renal progenitors in a self-renewing compartment
- name: Blocked Nephron Differentiation
description: >-
Wilms tumor arises from nephrogenic rests - foci of embryonic blastemal cells
that persist beyond the normal period of nephrogenesis. These cells retain
proliferative capacity but fail to undergo terminal differentiation into
mature nephrons. Loss of WT1 in nephrogenic rests may leave these premalignant
clones vulnerable to malignant transformation.
cell_types:
- preferred_term: metanephric mesenchyme stem cell
term:
id: CL:0000324
label: metanephric mesenchyme stem cell
biological_processes:
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
- preferred_term: nephron development
modifier: ABNORMAL
term:
id: GO:0072006
label: nephron development
evidence:
- reference: PMID:37916284
reference_title: "Wilms' tumor gene 1: lessons from the interface between kidney development and cancer."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Loss of WT1 in nephrogenic rests may leave these premalignant clones with
inadequate DNA repair enzymes and may disturb the epigenetic landscape.
explanation: >-
Supports the concept that nephrogenic rests with WT1 loss are premalignant
precursors of Wilms tumor.
- reference: PMID:37385707
reference_title: "Wilms Tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Wilms tumor (WT), or nephroblastoma, is the most common primary malignant renal
tumor of childhood. It is an embryonal tumor that develops from remnants of
immature kidney.
explanation: >-
Confirms Wilms tumor arises from embryonal remnants of immature kidney tissue.
downstream:
- target: Persistent Blastemal Progenitor State
description: Developmental arrest preserves proliferative embryonal renal cells
- name: IGF2 Loss of Imprinting
description: >-
Loss of imprinting at 11p15, leading to biallelic IGF2 expression, occurs
in approximately 70% of Wilms tumors. IGF2 is a major fetal growth factor
and its overexpression promotes proliferation of embryonic renal cells. This
epigenetic alteration is also the mechanism underlying Beckwith-Wiedemann syndrome,
which confers increased Wilms tumor risk.
gene:
preferred_term: IGF2
modifier: INCREASED
term:
id: hgnc:5466
label: IGF2
gene_products:
- preferred_term: IGF2
term:
id: NCIT:C16744
label: Insulin-Like Growth Factor II
biological_processes:
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
evidence:
- reference: PMID:25018051
reference_title: "The development of Wilms tumor: from WT1 and microRNA to animal models."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
epigenetic changes, particularly the loss of imprinting of the DNA region
encoding the major fetal growth factor IGF2, which results in its biallelic
over-expression, are closely associated with the development of many Wilms
tumors.
explanation: >-
Confirms loss of imprinting at IGF2 locus leading to biallelic overexpression
in Wilms tumor development.
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
While only 3% of patients without LOH/LOI relapsed, 20% with LOH 11p15 and
25% with LOI 11p15 relapsed
explanation: >-
Demonstrates the prognostic significance of 11p15 LOH/LOI in Wilms tumor,
confirming its role in tumor biology.
downstream:
- target: Persistent Blastemal Progenitor State
description: Biallelic IGF2 expression expands fetal renal progenitors
- name: MicroRNA Processing Defect
description: >-
DROSHA and DICER1 lesions derepress microRNA target genes controlling
differentiation and proliferation, reinforcing a self-renewing mesenchymal
state in Wilms tumor.
genes:
- preferred_term: DROSHA
term:
id: hgnc:17904
label: DROSHA
- preferred_term: DICER1
term:
id: hgnc:17098
label: DICER1
cell_types:
- preferred_term: metanephric mesenchyme stem cell
term:
id: CL:0000324
label: metanephric mesenchyme stem cell
biological_processes:
- preferred_term: cell differentiation
modifier: DECREASED
term:
id: GO:0030154
label: cell differentiation
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
evidence:
- reference: PMID:25018051
reference_title: "The development of Wilms tumor: from WT1 and microRNA to animal models."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Recent investigations also revealed that mutations of Drosha and Dicer, the
RNases required for miRNA generation, and Dis3L2, the 3'-5' exonuclease that
normally degrades miRNAs and mRNAs, could cause predisposition to Wilms tumors,
demonstrating that miRNA can play a pivotal role in Wilms tumor development.
explanation: >-
Supports disrupted microRNA biogenesis as a recurrent Wilms tumor mechanism.
downstream:
- target: Persistent Blastemal Progenitor State
description: miRNA dysregulation reinforces the undifferentiated proliferative compartment
- name: Nephron Progenitor Self-Renewal
description: >-
SIX1 and SIX2 hotspot mutations reinforce the embryonal nephron progenitor
transcriptional program in high-risk blastemal Wilms tumors, preserving
proliferative potential and chemotherapy resistance.
genes:
- preferred_term: SIX1
term:
id: hgnc:10887
label: SIX1
- preferred_term: SIX2
term:
id: hgnc:10888
label: SIX2
cell_types:
- preferred_term: nephrogenic zone cell
term:
id: CL:0009019
label: nephrogenic zone cell
biological_processes:
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
- preferred_term: metanephros development
modifier: ABNORMAL
term:
id: GO:0001656
label: metanephros development
evidence:
- reference: PMID:25670083
reference_title: "Mutations in the SIX1/2 pathway and the DROSHA/DGCR8 miRNA microprocessor complex underlie high-risk blastemal type Wilms tumors."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Recurrent mutations included a hotspot mutation (Q177R) in the homeo-domain
of SIX1 and SIX2 in tumors with high proliferative potential (18.1% of
blastemal cases)
explanation: >-
Supports a SIX1/SIX2-driven progenitor program in proliferative blastemal
Wilms tumors.
downstream:
- target: Persistent Blastemal Progenitor State
description: SIX1/SIX2-mutant progenitors retain a proliferative embryonal identity
- name: Persistent Blastemal Progenitor State
description: >-
Multiple Wilms tumor drivers converge on persistence of embryonal renal
blastemal cells with high proliferative capacity and failed terminal
differentiation.
cell_types:
- preferred_term: metanephric mesenchyme stem cell
term:
id: CL:0000324
label: metanephric mesenchyme stem cell
- preferred_term: nephrogenic zone cell
term:
id: CL:0009019
label: nephrogenic zone cell
biological_processes:
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
- preferred_term: nephron development
modifier: ABNORMAL
term:
id: GO:0072006
label: nephron development
evidence:
- reference: PMID:25670083
reference_title: "Mutations in the SIX1/2 pathway and the DROSHA/DGCR8 miRNA microprocessor complex underlie high-risk blastemal type Wilms tumors."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Recurrent mutations included a hotspot mutation (Q177R) in the homeo-domain
of SIX1 and SIX2 in tumors with high proliferative potential (18.1% of
blastemal cases)
explanation: >-
Human tumor genomics support persistence of a highly proliferative blastemal
compartment in high-risk Wilms tumor.
downstream:
- target: Wilms Tumor Outgrowth
description: Persisting blastemal clones expand into overt nephroblastoma
- name: Wilms Tumor Outgrowth
description: >-
Persisting embryonal renal progenitors expand into nephroblastoma, an
embryonal kidney malignancy with blastemal, epithelial, and stromal elements.
locations:
- preferred_term: kidney
term:
id: UBERON:0002113
label: kidney
biological_processes:
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
evidence:
- reference: PMID:37385707
reference_title: "Wilms Tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Wilms tumor (WT), or nephroblastoma, is the most common primary malignant renal
tumor of childhood. It is an embryonal tumor that develops from remnants of
immature kidney.
explanation: >-
Supports the endpoint of embryonal renal outgrowth into overt Wilms tumor.
downstream:
- target: TP53-Deficient Anaplastic Progression
description: Acquisition of TP53 dysfunction drives aggressive anaplastic evolution in a subset of tumors
- name: TP53-Deficient Anaplastic Progression
description: >-
In anaplastic Wilms tumor, TP53 dysfunction promotes progression toward an
aggressive, treatment-resistant state with impaired genome surveillance.
gene:
preferred_term: TP53
modifier: DECREASED
term:
id: hgnc:11998
label: TP53
biological_processes:
- preferred_term: apoptotic process
modifier: DECREASED
term:
id: GO:0006915
label: apoptotic process
- preferred_term: DNA repair
modifier: DECREASED
term:
id: GO:0006281
label: DNA repair
evidence:
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
careful analysis including copy number assessment and immunohistochemistry,
as well as confirming that anaplasia was present in the portion of tumor
undergoing mutation analysis, indicated that nearly all anaplastic WT have
TP53 mutations if one looks hard enough
explanation: >-
Supports TP53 dysfunction as the defining progression mechanism in anaplastic
Wilms tumor.
phenotypes:
- category: Abdominal
name: Abdominal Mass
frequency: VERY_FREQUENT
diagnostic: true
description: >-
A palpable abdominal mass is the most common presenting finding, often
noticed incidentally by parents during bathing. The mass is typically
smooth, firm, and does not cross the midline.
phenotype_term:
preferred_term: Abdominal mass
term:
id: HP:0031500
label: Abdominal mass
evidence:
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In most cases, a parent will identify an abdominal mass upon bathing or dressing
their child, or a pediatrician will palpate a mass upon examining the child
during a routine well-child visit.
explanation: >-
Confirms abdominal mass as the most common presenting finding in Wilms tumor.
- category: Genitourinary
name: Hematuria
frequency: FREQUENT
description: >-
Gross or microscopic hematuria occurs in patients presenting with Wilms tumor
and may be the presenting symptom.
phenotype_term:
preferred_term: Hematuria
term:
id: HP:0000790
label: Hematuria
evidence:
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
However, up to 35% of patients can present with either hematuria, hypertension,
fever, or flank pain
explanation: >-
Confirms hematuria as a presenting symptom in a subset of Wilms tumor patients.
- category: Cardiovascular
name: Hypertension
frequency: FREQUENT
description: >-
Hypertension occurs in patients with Wilms tumor due to renin secretion
by the tumor or renal artery compression.
phenotype_term:
preferred_term: Hypertension
term:
id: HP:0000822
label: Hypertension
evidence:
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
However, up to 35% of patients can present with either hematuria, hypertension,
fever, or flank pain
explanation: >-
Confirms hypertension as a presenting symptom in Wilms tumor patients.
- category: Constitutional
name: Fever
frequency: OCCASIONAL
description: >-
Low-grade fever may occur as a constitutional symptom.
phenotype_term:
preferred_term: Fever
term:
id: HP:0001945
label: Fever
evidence:
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
However, up to 35% of patients can present with either hematuria, hypertension,
fever, or flank pain
explanation: >-
Lists fever among presenting symptoms in Wilms tumor patients.
- category: Ophthalmologic
name: Aniridia
frequency: OCCASIONAL
description: >-
Aniridia (absence of the iris) occurs in WAGR syndrome, caused by contiguous
deletion of WT1 and PAX6 on chromosome 11p13. Children with sporadic aniridia
require screening for Wilms tumor.
phenotype_term:
preferred_term: Aniridia
term:
id: HP:0000526
label: Aniridia
evidence:
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
More than 15 different syndromes are associated with WT, including WAGR
(Wilms tumor, aniridia, genitourinary abnormalities, and a range of
developmental delays)
explanation: >-
Confirms aniridia as a feature of WAGR syndrome associated with Wilms tumor.
- category: Growth
name: Hemihypertrophy
frequency: OCCASIONAL
description: >-
Hemihypertrophy (asymmetric overgrowth) is associated with Beckwith-Wiedemann
syndrome and increased Wilms tumor risk. Children with hemihypertrophy
require tumor surveillance.
phenotype_term:
preferred_term: Hemihypertrophy
term:
id: HP:0001528
label: Hemihypertrophy
evidence:
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Beckwith-Wiedemann (embryonal tumors, macrosomia, macroglossia, hemihypertrophy,
visceromegaly, omphalocele, neonatal hypoglycemia, and ear creases/pits)
explanation: >-
Confirms hemihypertrophy as a feature of Beckwith-Wiedemann syndrome
associated with Wilms tumor predisposition.
- category: Abdominal
name: Abdominal Pain
frequency: OCCASIONAL
description: >-
Flank pain may be a presenting symptom, and rarely, patients present with
acute abdomen in the setting of tumor rupture.
phenotype_term:
preferred_term: Abdominal pain
term:
id: HP:0002027
label: Abdominal pain
evidence:
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
However, up to 35% of patients can present with either hematuria, hypertension,
fever, or flank pain
explanation: >-
Confirms flank pain as one of the presenting symptoms of Wilms tumor.
histopathology:
- name: Triphasic Histology
subtype: Mixed Cell Type
finding_term:
preferred_term: triphasic pattern
term:
id: NCIT:C35928
label: Triphasic Pattern
frequency: VERY_FREQUENT
description: >-
Wilms tumor classically shows triphasic histology with blastemal, stromal,
and epithelial components. The relative proportions of these components
vary and have prognostic significance.
evidence:
- reference: PMID:27512769
reference_title: "Wilms’ Tumour – Histology and Differential Diagnosis."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Typically, WT comprises three histological components namely blastemal,
epithelial and stromal. The proportion and the degree of maturation of these
components vary significantly, making the histological appearance of each tumour
unique. Classical triphasic WT rarely presents diagnostic difficulty for
pathologists
explanation: >-
Directly describes the triphasic histological composition of Wilms tumor
with blastemal, epithelial, and stromal components.
- name: Blastemal Predominant Histology
subtype: Blastemal Predominant
finding_term:
preferred_term: Blastema Predominant Kidney Wilms Tumor
term:
id: NCIT:C9147
label: Blastema Predominant Kidney Wilms Tumor
description: >-
Blastemal-predominant histology is a high-risk Wilms tumor pattern,
particularly after preoperative chemotherapy, and reflects persistence of
residual blastemal cells with relative chemotherapy resistance.
evidence:
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
High-risk histology includes blastemal-type tumors, as a predominance of
residual blastemal cells is a marker of chemotherapy resistance.
explanation: >-
Directly supports blastemal-predominant Wilms tumor as a distinct
high-risk histologic subtype associated with chemotherapy resistance.
- reference: PMID:27512769
reference_title: "Wilms’ Tumour – Histology and Differential Diagnosis."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
WT with diffuse anaplasia and WT with blastemal predominance (after
preoperative chemotherapy) are regarded as high-risk tumours and require more
aggressive treatment.
explanation: >-
Independent pathology review supporting blastemal predominance as a
clinically meaningful high-risk Wilms tumor pattern.
- name: Epithelial Predominant Histology
subtype: Epithelial Predominant
finding_term:
preferred_term: Epithelial Predominant Kidney Wilms Tumor
term:
id: NCIT:C9146
label: Epithelial Predominant Kidney Wilms Tumor
description: >-
Epithelial-predominant Wilms tumor emphasizes tubule- and glomeruloid-like
epithelial differentiation and generally falls into a more favorable
post-chemotherapy histologic group.
evidence:
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Stromal and epithelia-type nephroblastoma show an excellent outcome after
preoperative chemotherapy
explanation: >-
Supports epithelial-type nephroblastoma as a recognized histologic group
with favorable outcomes after preoperative chemotherapy.
- reference: PMID:27512769
reference_title: "Wilms’ Tumour – Histology and Differential Diagnosis."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Typically, WT comprises three histological components namely blastemal,
epithelial and stromal. The proportion and the degree of maturation of these
components vary significantly, making the histological appearance of each tumour
unique.
explanation: >-
Supports epithelial-predominant Wilms tumor as part of the variable
component balance within Wilms histology.
- name: Stromal Predominant Histology
subtype: Stromal Predominant
finding_term:
preferred_term: Stromal Predominant Kidney Wilms Tumor
term:
id: NCIT:C9148
label: Stromal Predominant Kidney Wilms Tumor
description: >-
Stromal-predominant Wilms tumor emphasizes mesenchymal differentiation and,
like epithelial-type nephroblastoma, is generally associated with favorable
outcomes after preoperative chemotherapy.
evidence:
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Stromal and epithelia-type nephroblastoma show an excellent outcome after
preoperative chemotherapy
explanation: >-
Supports stromal-type nephroblastoma as a recognized histologic group with
favorable post-chemotherapy outcomes.
- reference: PMID:27512769
reference_title: "Wilms’ Tumour – Histology and Differential Diagnosis."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Typically, WT comprises three histological components namely blastemal,
epithelial and stromal. The proportion and the degree of maturation of these
components vary significantly, making the histological appearance of each tumour
unique.
explanation: >-
Supports stromal-predominant Wilms tumor as part of the variable
component balance within Wilms histology.
- name: Anaplasia
subtype: Anaplastic
finding_term:
preferred_term: Anaplastic Wilms Tumor
term:
id: NCIT:C6952
label: Anaplastic Kidney Wilms Tumor
description: >-
Anaplasia is characterized by extreme nuclear enlargement and pleomorphism
with atypical mitoses. It may be focal or diffuse, with diffuse anaplasia
conferring significantly worse prognosis. Nearly all anaplastic Wilms tumors
harbor TP53 mutations.
evidence:
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
careful analysis including copy number assessment and immunohistochemistry,
as well as confirming that anaplasia was present in the portion of tumor
undergoing mutation analysis, indicated that nearly all anaplastic WT have
TP53 mutations if one looks hard enough
explanation: >-
Confirms near-universal TP53 mutation in anaplastic Wilms tumors.
biochemical:
- name: IGF2 Overexpression
biomarker_term:
preferred_term: IGF2
term:
id: NCIT:C16744
label: Insulin-Like Growth Factor II
notes: >-
IGF2 overexpression is a hallmark Wilms tumor biomarker linked to 11p15
loss of imprinting and biallelic fetal growth-factor expression, particularly
in blastemal and predisposition-associated tumors.
evidence:
- reference: PMID:25018051
reference_title: "The development of Wilms tumor: from WT1 and microRNA to animal models."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
epigenetic changes, particularly the loss of imprinting of the DNA region
encoding the major fetal growth factor IGF2, which results in its biallelic
over-expression, are closely associated with the development of many Wilms
tumors.
explanation: >-
Supports IGF2 overexpression as a canonical Wilms tumor biomarker driven by
11p15 epigenetic dysregulation.
- name: WT1 Protein Expression
biomarker_term:
preferred_term: WT1 protein
term:
id: NCIT:C17549
label: Wilms Tumor Protein
notes: >-
WT1 protein expression is widely used in the diagnostic workup of pediatric
renal tumors and nephrogenic lesions, complementing genomic assessment of
WT1 loss or predisposition.
genetic:
- name: WT1 Mutations
association: Tumor Suppressor Loss
gene_term:
preferred_term: WT1
term:
id: hgnc:12796
label: WT1
notes: >-
WT1 mutations occur in 10-15% of sporadic Wilms tumors. Germline WT1 mutations
cause predisposition syndromes (WAGR, Denys-Drash, Frasier). WT1 is a transcription
factor essential for kidney development.
evidence:
- reference: PMID:37916284
reference_title: "Wilms' tumor gene 1: lessons from the interface between kidney development and cancer."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In 1990, mutations of the Wilms' tumor-1 gene (WT1), encoding a transcription
factor in the embryonic kidney, were found in 10-15% of Wilms' tumors; germline
WT1 mutations were associated with hereditary syndromes involving glomerular and
reproductive tract dysplasia.
explanation: >-
Confirms WT1 mutation frequency and germline association with hereditary
syndromes.
- name: CTNNB1 Mutations
association: Oncogenic Driver Mutations
gene_term:
preferred_term: CTNNB1
term:
id: hgnc:2514
label: CTNNB1
notes: >-
Activating mutations in CTNNB1 (beta-catenin) occur in approximately 15%
of Wilms tumors, leading to constitutive Wnt pathway activation.
evidence:
- reference: PMID:25018051
reference_title: "The development of Wilms tumor: from WT1 and microRNA to animal models."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This has been illustrated by the findings that mutations of Wnt/β-catenin
pathway-related WT1, β-catenin, and WTX together account for about one-third of
Wilms tumor cases.
explanation: >-
Confirms CTNNB1 as one of the key mutated genes in Wilms tumor
contributing to Wnt pathway activation.
- name: WTX (AMER1) Mutations
association: Tumor Suppressor Loss
gene_term:
preferred_term: AMER1
term:
id: hgnc:26837
label: AMER1
notes: >-
WTX inactivation occurs in 15-20% of Wilms tumors. WTX negatively regulates
Wnt signaling, and its loss leads to pathway activation.
evidence:
- reference: PMID:25018051
reference_title: "The development of Wilms tumor: from WT1 and microRNA to animal models."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This has been illustrated by the findings that mutations of Wnt/β-catenin
pathway-related WT1, β-catenin, and WTX together account for about one-third of
Wilms tumor cases.
explanation: >-
Confirms WTX (AMER1) as one of the key mutated genes in Wilms tumor.
- name: Loss of 11p15 Imprinting
association: Epigenetic Alteration
gene_term:
preferred_term: IGF2
term:
id: hgnc:5466
label: IGF2
notes: >-
Loss of imprinting at 11p15, leading to biallelic IGF2 expression, occurs
in approximately 70% of Wilms tumors. This is also the mechanism in
Beckwith-Wiedemann syndrome.
evidence:
- reference: PMID:25018051
reference_title: "The development of Wilms tumor: from WT1 and microRNA to animal models."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
epigenetic changes, particularly the loss of imprinting of the DNA region
encoding the major fetal growth factor IGF2, which results in its biallelic
over-expression, are closely associated with the development of many Wilms
tumors.
explanation: >-
Confirms loss of imprinting at IGF2/11p15 locus in Wilms tumor development.
- name: Chromosome 1q Gain
association: Prognostic Marker
notes: >-
Gain of chromosome 1q is one of the most commonly observed cytogenetic
abnormalities in Wilms tumor, seen in approximately 30% of patients.
It is associated with inferior event-free survival and overall survival
across all tumor stages.
evidence:
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
gain of chromosome 1q is one of the most commonly observed cytogenetic
abnormalities in WT, seen in as many as 30% of patients
explanation: >-
Confirms 1q gain frequency and its status as a common cytogenetic
abnormality in Wilms tumor.
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
A retrospective analysis of more than 1000 patients in NWTS-5 demonstrated
that 1q gain was associated with inferior EFS and OS across all tumor stages
explanation: >-
Demonstrates prognostic significance of 1q gain across all stages.
- name: Combined LOH 1p/16q
association: Prognostic Marker
notes: >-
Loss of heterozygosity at chromosomes 1p and 16q occurs in approximately
5% of favorable histology Wilms tumors and is associated with increased
risk of relapse. Escalated therapy can overcome this adverse prognostic factor.
evidence:
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Combined LOH 1p and 16q has limited impact as a prognostic marker because
only 5% of favorable histology WT carry this molecular change.
explanation: >-
Confirms frequency and prognostic relevance of combined 1p/16q LOH.
- name: TP53 Mutations
association: Anaplasia Driver
subtype: Anaplastic
gene_term:
preferred_term: TP53
term:
id: hgnc:11998
label: TP53
notes: >-
TP53 mutations are found in approximately 50-60% of diffuse anaplastic
Wilms tumors. TP53 dysfunction drives anaplastic transformation and is
associated with poor prognosis and therapy resistance.
evidence:
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
careful analysis including copy number assessment and immunohistochemistry,
as well as confirming that anaplasia was present in the portion of tumor
undergoing mutation analysis, indicated that nearly all anaplastic WT have
TP53 mutations if one looks hard enough
explanation: >-
Confirms near-universal TP53 mutation in anaplastic Wilms tumors when
thoroughly assessed.
- name: DROSHA and DICER1 Mutations
association: miRNA Processing Defect
notes: >-
Mutations in DROSHA and DICER1, the RNases required for miRNA generation,
can cause predisposition to Wilms tumors. DROSHA mutations are correlated
with a self-renewing mesenchymal state and aberrant redox metabolism.
Wilms tumor cells lacking microRNAs are sensitized to ferroptotic cell death
through inhibition of GPX4.
evidence:
- reference: PMID:25018051
reference_title: "The development of Wilms tumor: from WT1 and microRNA to animal models."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Recent investigations also revealed that mutations of Drosha and Dicer, the
RNases required for miRNA generation, and Dis3L2, the 3'-5' exonuclease that
normally degrades miRNAs and mRNAs, could cause predisposition to Wilms tumors,
demonstrating that miRNA can play a pivotal role in Wilms tumor development.
explanation: >-
Confirms mutations in miRNA processing enzymes as a mechanism of Wilms
tumor predisposition.
- name: SIX1/SIX2 Mutations
association: Nephron Progenitor Program
notes: >-
Recurrent SIX1/SIX2 Q177R homeodomain mutations occur in 18.1% of
blastemal-type Wilms tumors. These mutations are associated with high
proliferative potential and chemotherapy-resistant blastemal tumors.
evidence:
- reference: PMID:25670083
reference_title: "Mutations in the SIX1/2 pathway and the DROSHA/DGCR8 miRNA microprocessor complex underlie high-risk blastemal type Wilms tumors."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Recurrent mutations included a hotspot mutation (Q177R) in the homeo-domain
of SIX1 and SIX2 in tumors with high proliferative potential (18.1% of
blastemal cases)
explanation: >-
Landmark genomic study directly demonstrating recurrent SIX1/SIX2 Q177R
mutations in 18.1% of blastemal-type Wilms tumors.
treatments:
- name: Surgical Resection
description: >-
Nephrectomy is the primary treatment for unilateral Wilms tumor. In North
America (COG), upfront nephrectomy provides staging information and allows
for immediate histologic diagnosis and molecular analysis. In Europe (SIOP),
preoperative chemotherapy is given first. Both approaches achieve similar
survival rates.
treatment_term:
preferred_term: nephrectomy
term:
id: NCIT:C15284
label: Nephrectomy
evidence:
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The COG approach of upfront nephrectomy allows for immediate histologic
diagnosis, molecular analysis, and accurate local staging assessment.
explanation: >-
Confirms the role of nephrectomy as primary surgical approach in COG trials.
- reference: PMID:37385707
reference_title: "Wilms Tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Advances in multimodal therapy including surgery, chemotherapy, and radiation
therapy given according to risk stratification have allowed most patients to
achieve survival rates in excess of 90%.
explanation: >-
Confirms the multimodal approach including surgery achieves >90% survival.
- name: Chemotherapy
description: >-
Actinomycin D and vincristine form the backbone of treatment for favorable
histology tumors. Doxorubicin and other agents are added for higher-stage
or anaplastic tumors. Cyclophosphamide and etoposide are added for the
highest-risk patients.
treatment_term:
preferred_term: chemotherapy
term:
id: NCIT:C15632
label: Chemotherapy
therapeutic_agent:
- preferred_term: dactinomycin
term:
id: NCIT:C412
label: Dactinomycin
- preferred_term: vincristine
term:
id: NCIT:C933
label: Vincristine
- preferred_term: doxorubicin
term:
id: NCIT:C456
label: Doxorubicin
evidence:
- reference: PMID:39034876
reference_title: "Late effects of Wilms' tumor treatment."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The most common drugs used were vincristine and actinomycin D (78%). Only
12 patients (28%) received anthracyclines.
explanation: >-
Confirms vincristine and dactinomycin as backbone chemotherapy with
anthracyclines reserved for higher-risk patients.
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Stepwise advances made by the National Wilms Tumor Study Group (NWTSG),
which was succeeded by the Children's Oncology Group (COG), and the
International Society of Pediatric Oncology (SIOP) Renal Tumor Study Group
(RTSG) have not only improved survival to 90%, but have also decreased the
burden of therapy
explanation: >-
Confirms that stepwise refinement of chemotherapy has improved survival
to 90%.
- name: Radiation Therapy
description: >-
Flank radiation is used for stage III tumors and higher. Whole abdominal
radiation is used for tumor rupture or diffuse peritoneal contamination.
Whole lung irradiation is used for pulmonary metastases that fail to
respond completely to chemotherapy.
treatment_term:
preferred_term: radiation therapy
term:
id: NCIT:C15313
label: Radiation Therapy
evidence:
- reference: PMID:32893998
reference_title: "Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The objectives for the treatment of Wilms tumor in both the Children's Oncology
Group (COG) and the International Society of Paediatric Oncology (SIOP) have
focused on improving cure rates and minimizing toxicity by limiting the use of
radiation and doxorubicin.
explanation: >-
Confirms radiation therapy is part of standard treatment while efforts
focus on minimizing its use to reduce toxicity.
- name: Selinexor
description: >-
Selinexor is an oral XPO1 inhibitor under clinical evaluation for recurrent
or refractory Wilms tumor and other pediatric solid tumors.
treatment_term:
preferred_term: pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: selinexor
term:
id: NCIT:C102546
label: Selinexor
evidence:
- reference: clinicaltrials:NCT05985161
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The purpose of this study is to find out whether selinexor is an effective
treatment for people who have a relapsed/refractory Wilms tumor, rhabdoid
tumor, MPNST, or another solid tumor that makes a higher than normal amount
of XPO1 or has genetic changes that increase the activity of XP01.
explanation: >-
Supports selinexor as an investigational Wilms tumor therapy through an
active Wilms-specific cohort in a pediatric solid tumor trial.
prevalence:
- population: Worldwide
notes: >-
Estimated incidence of about 9 per million children under 15 years old
in the United States and Canada, affecting 1 in 10,000 children. Similar
rates in Europe, Australia, and New Zealand with lower rates in Asia
and higher rates in parts of Africa.
evidence:
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In the United States and Canada, the estimated incidence is about 9 per
million children under 15 years old, affecting 1 in 10,000 children
explanation: >-
Provides incidence data for Wilms tumor in North America.
progression:
- phase: Diagnosis
age_range: Under 5 years
notes: >-
Most cases are diagnosed in children under 5 years of age. Increasing patient
age is associated with increased risk of recurrence and worse outcome.
evidence:
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Because WT is a malignant embryonal tumor, most cases are diagnosed in
children under the age of 5 years.
explanation: >-
Confirms typical age at diagnosis for Wilms tumor.
classifications:
icdo_morphology:
classification_value: Embryonal Neoplasm
evidence:
- reference: PMID:37385707
reference_title: "Wilms Tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Wilms tumor (WT), or nephroblastoma, is the most common primary malignant renal
tumor of childhood. It is an embryonal tumor that develops from remnants of
immature kidney.
explanation: >-
Confirms Wilms tumor is an embryonal neoplasm arising from immature kidney.
harrisons_chapter:
- classification_value: cancer
evidence:
- reference: PMID:37385707
reference_title: "Wilms Tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Wilms tumor (WT), or nephroblastoma, is the most common primary malignant renal
tumor of childhood.
explanation: >-
Confirms Wilms tumor is a malignant neoplasm classified under cancer.
- classification_value: solid tumor
evidence:
- reference: PMID:33394739
reference_title: "New approaches to risk stratification for Wilms tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Wilms tumor (WT) is the second most common extracranial solid tumor and the
most common malignant renal tumor in children.
explanation: >-
Confirms Wilms tumor is classified as a solid tumor.
mappings:
icd10cm_mappings:
- term:
id: ICD10CM:C64.9
label: Malignant neoplasm of unspecified kidney, except renal pelvis
mapping_predicate: skos:closeMatch
mapping_source: ICD-10-CM
mapping_justification: >-
ICD-10-CM C64 category covers malignant neoplasms of kidney including
nephroblastoma/Wilms tumor. C64.9 is used when laterality is unspecified.
C64.1 (right) and C64.2 (left) specify laterality.
mondo_mappings:
- term:
id: MONDO:0006058
label: Wilms tumor
mapping_predicate: skos:exactMatch
mapping_source: MONDO
mapping_justification: Primary MONDO disease identifier for this Wilms tumor entry.
ncit_mappings:
- term:
id: NCIT:C3267
label: Wilms Tumor
mapping_predicate: skos:exactMatch
mapping_source: NCIT
mapping_justification: Primary NCIT disease concept corresponding to Wilms tumor.
datasets:
- accession: dbgap:phs000471
title: "TARGET: Kidney, Wilms Tumor (WT)"
description: >-
TARGET high-risk Wilms tumor cohort with matched tumor-normal profiling,
including gene expression, copy number, methylation, whole genome sequencing,
and subset mRNA-seq, miRNA-seq, and whole exome sequencing.
organism:
preferred_term: human
term:
id: NCBITaxon:9606
label: Homo sapiens
data_type: MULTI_OMICS
sample_types:
- preferred_term: Wilms tumor tissue
tissue_term:
preferred_term: kidney
term:
id: UBERON:0002113
label: kidney
sample_count: 130
conditions:
- high-risk Wilms tumor
- anaplastic Wilms tumor
- relapsed favorable histology Wilms tumor
notes: >-
dbGaP describes 130 fully characterized high-risk Wilms tumor cases with
tumor-normal pairs, selected largely from anaplastic tumors or favorable
histology tumors that relapsed.
clinical_trials:
- name: NCT05985161
phase: PHASE_II
description: >-
Multi-center phase II study of selinexor in recurrent or refractory Wilms
tumor and other pediatric solid tumors, including a dedicated Wilms tumor
cohort.
evidence:
- reference: clinicaltrials:NCT05985161
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The purpose of this study is to find out whether selinexor is an effective
treatment for people who have a relapsed/refractory Wilms tumor, rhabdoid
tumor, MPNST, or another solid tumor that makes a higher than normal amount
of XPO1 or has genetic changes that increase the activity of XP01.
explanation: >-
Supports a Wilms-specific phase II selinexor clinical trial for recurrent
or refractory disease.
Question: You are an expert researcher providing comprehensive, well-cited information.
Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies
Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.
Please provide a comprehensive research report on the pathophysiology of Wilms Tumor. Focus on the molecular and cellular mechanisms underlying disease progression.
Structure your response as a narrative that could be used to populate a disease knowledge base entry with: - Pathophysiology description - Gene/protein annotations with ontology terms (HGNC, GO) - Phenotype associations (HP terms) - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Evidence items with PMIDs
Wilms tumor is best understood as a developmental cancer in which aberrant fetal kidney programs persist or are reactivated, often via early embryonic events that create nephrogenic rests and/or clonal nephrogenesis, followed by acquisition of additional genetic/epigenetic driver events that lock cells into progenitor-like states and enable malignant growth (perotti2024hallmarkdiscoveriesin pages 6-10, perotti2024hallmarkdiscoveriesin pages 25-29). The dominant mechanistic axes supported by recent synthesis and primary studies include: 11p15 imprinting/IGF2 dysregulation, WT1 loss, WNT/β-catenin activation (CTNNB1; AMER1/WTX), microRNA-processing defects (DROSHA/DGCR8/DICER1), SIX1/SIX2 nephron progenitor dysregulation, and (in high-risk subsets) TP53-driven anaplasia with additional genomic instability, including 1q gain and LOH 1p/16q that are used in risk stratification (perotti2024hallmarkdiscoveriesin pages 10-14, perotti2024hallmarkdiscoveriesin pages 14-17, perotti2024hallmarkdiscoveriesin pages 17-21, cantoni2026tumormicroenvironmentand pages 2-4).
| Mechanism/pathway | Key genes/proteins (HGNC symbols) | Cellular process (GO-style phrase) | Cell types/anatomy (CL/UBERON terms as text) | Evidence highlights with quantitative stats | Key recent sources (author, year, journal) with URL | Evidence citation IDs (pqac-...) |
|---|---|---|---|---|---|---|
| 11p15 imprinting / IGF2-H19 dysregulation | IGF2, H19, KCNQ1OT1, KCNQ1, WT1 | genomic imprinting; regulation of IGF signaling; epigenetic regulation of gene expression | embryonic renal progenitor / nephrogenic rest-like cells; blastemal tumor cells; kidney (UBERON:kidney), chromosome 11p15.5 locus | 11p15 alterations are among the most frequent WT events; IGF2 overexpression occurs in up to 70% of sporadic tumors and is near-universal in blastemal-type tumors. In bilateral WT, 58/99 (58.6%) tumors had H19/ICR1 loss of imprinting and 25/99 (25.2%) had 11p15.5 LOH; 29/30 (96.7%) synchronous tumors were concordant for 11p15.5 status. In 18/19 (94.7%) LOH tumors, breakpoints overlapped WT1/11p13, supporting coupled WT1/IGF2 dysregulation. | Perotti et al., 2024, Nat Rev Urol — https://doi.org/10.1038/s41585-023-00824-0; Murphy et al., 2023, Nat Commun — https://doi.org/10.1038/s41467-023-43730-0; Nirgude et al., 2024, Br J Cancer — https://doi.org/10.1038/s41416-023-02538-x | (perotti2024hallmarkdiscoveriesin pages 10-14, murphy2023geneticandepigenetic pages 4-5, murphy2023geneticandepigenetic pages 1-2, nirgude2024cancerpredispositionsignaling pages 1-2) |
| WT1 tumor suppressor / developmental regulator | WT1, IGF2, CTNNB1 | kidney development; nephron progenitor differentiation; tumor suppressor activity; transcription regulation | metanephric mesenchyme / embryonic renal progenitors; nephrogenic rests; kidney (UBERON:kidney) | WT1 mutations occur in ~6–20% of sporadic tumors and define a classic predisposition pathway. In bilateral WT, germline WT1 variants were found in 9/61 (14.8%) patients, and all 14 tumors from these patients showed 11p15.5 LOH; CTNNB1 mutations occurred in 10/14 (71.4%) of this WT1-associated set, supporting a stereotyped WT1 → 11p LOH/IGF2 activation → CTNNB1 sequence. | Perotti et al., 2024, Nat Rev Urol — https://doi.org/10.1038/s41585-023-00824-0; Murphy et al., 2023, Nat Commun — https://doi.org/10.1038/s41467-023-43730-0 | (perotti2024hallmarkdiscoveriesin pages 6-10, murphy2023geneticandepigenetic pages 1-2, murphy2023geneticandepigenetic pages 7-9) |
| WNT/β-catenin activation | CTNNB1, AMER1, WT1 | canonical Wnt signaling; β-catenin stabilization; regulation of progenitor proliferation and myogenic differentiation | blastemal tumor cells; epithelial/prototubular elements; embryonic kidney (UBERON:kidney) | CTNNB1 activating mutations occur in ~15% of WTs; ~65% affect exon 3, causing loss of phosphorylation sites and β-catenin stabilization. There is a strong WT1-CTNNB1 association: 19/20 CTNNB1-mutant tumors also carried WT1 mutations (p = 3.6 × 10^-13). AMER1 inactivation has been reported in up to 30% of tumors in initial studies (additional screens 7–18%). | Perotti et al., 2024, Nat Rev Urol — https://doi.org/10.1038/s41585-023-00824-0 | (perotti2024hallmarkdiscoveriesin pages 14-17, perotti2024hallmarkdiscoveriesin pages 10-14) |
| miRNA processing defects and ferroptosis vulnerability | DROSHA, DGCR8, DICER1, XPO5, GPX4, ACSL4, CCND2 | miRNA biogenesis; post-transcriptional gene silencing; maintenance of mesenchymal progenitor state; regulation of ferroptotic cell death | self-renewing mesenchymal/blastemal tumor cells; embryonic renal progenitors; kidney (UBERON:kidney) | miRNA-processing gene mutations are enriched in blastemal WT: DROSHA/DGCR8 in ~18.2% of blastemal cases; DROSHA ~10% in favorable-histology WT; DGCR8 ~4.5%. In bilateral WT, DROSHA mutations were seen in 7/85 (8.2%) tumors and DGCR8 in 4/85 (4.7%). DROSHA loss de-represses miRNA targets, increases CCND2, and is associated with ACSL4/redox abnormalities that sensitize cells to GPX4 inhibition and ferroptosis. | Tiburcio et al., 2024, Mol Cancer Res — https://doi.org/10.1158/1541-7786.mcr-23-0930; Perotti et al., 2024, Nat Rev Urol — https://doi.org/10.1038/s41585-023-00824-0; Murphy et al., 2023, Nat Commun — https://doi.org/10.1038/s41467-023-43730-0 | (tiburcio2024drosharegulatesmesenchymal pages 1-3, perotti2024hallmarkdiscoveriesin pages 17-21, murphy2023geneticandepigenetic pages 4-5) |
| SIX1/SIX2 progenitor-state program | SIX1, SIX2 | maintenance of nephron progenitor cell population; regulation of cell cycle; kidney development; adhesion gene regulation | blastemal tumor cells; nephron progenitor/cap mesenchyme-like cells; kidney (UBERON:kidney) | Recurrent SIX1/SIX2 Q177R homeodomain mutations occur in 18.1% of blastemal cases and 4.3% overall. These are linked to a progenitor-like state, chemotherapy-resistant blastemal tumors, and altered cell-cycle, kidney-development, and adhesion programs. | Perotti et al., 2024, Nat Rev Urol — https://doi.org/10.1038/s41585-023-00824-0 | (perotti2024hallmarkdiscoveriesin pages 17-21, perotti2024hallmarkdiscoveriesin pages 14-17) |
| MYCN dysregulation | MYCN | positive regulation of cell proliferation; transcriptional amplification; oncogenic progenitor expansion | blastemal/anaplastic tumor cells; embryonic kidney-derived tumor compartments | MYCN gain/amplification and recurrent P44L mutation are described in WT; MYCN gain is associated with anaplastic histology and poor outcome. Reviews classify MYCN activation as one of the major transcriptional/mutational subclasses in WT. | Perotti et al., 2024, Nat Rev Urol — https://doi.org/10.1038/s41585-023-00824-0; Tiburcio et al., 2024, Mol Cancer Res — https://doi.org/10.1158/1541-7786.mcr-23-0930 | (perotti2024hallmarkdiscoveriesin pages 14-17, tiburcio2024drosharegulatesmesenchymal pages 1-3) |
| TP53 dysfunction and anaplasia | TP53 | DNA damage response; apoptotic signaling; anaplastic transformation | diffuse anaplastic tumor cells; high-risk Wilms tumor compartments; kidney tumor tissue | Diffuse anaplasia occurs in ~5–10% of WTs. TP53 is mutated in ~50–60% of diffuse anaplastic WTs, and TP53 immunopositivity is usually associated with anaplasia and poor prognosis. | Perotti et al., 2024, Nat Rev Urol — https://doi.org/10.1038/s41585-023-00824-0 | (perotti2024hallmarkdiscoveriesin pages 10-14) |
| Copy-number risk biomarkers | 1q gain; LOH 1p; LOH 16q; chromosome 12 gain | chromosomal instability; copy-number alteration-associated progression; relapse risk stratification | Wilms tumor tissue broadly; high-risk blastemal and anaplastic compartments | Combined LOH at 1p/16q is an established adverse biomarker in COG protocols. 1q gain occurs in ~20–30% of cases and is a strong predictor of poor outcome. In one 2024 genomic/modeling study, 1q gain was seen in 2 patients, combined LOH 1p/16q in 2 patients, and chromosome 12 gain (linked to relapse) in 2 patients. | Mittal et al., 2024, Commun Biol — https://doi.org/10.1038/s42003-024-06140-6; Cantoni et al., 2026, Cancers — https://doi.org/10.3390/cancers18060908; Lim & Loh, 2024, Cancers — https://doi.org/10.3390/cancers16173051 | (mittal2024targetingtrip13in pages 2-3, cantoni2026tumormicroenvironmentand pages 2-4, lim2024interethnicvariationsin pages 15-17) |
| XPO1 nuclear export dependency / selinexor vulnerability | XPO1, TRIP13 | nuclear export; regulation of cell survival; drug response | Wilms tumor cell lines and recurrent/refractory Wilms tumor; kidney tumor tissue | XPO1 was identified as a vulnerability in WT models; selinexor suppressed TRIP13 and synergized with doxorubicin in vivo/in vitro. A dedicated Phase II trial (NCT05985161) is recruiting for relapsed/refractory or high-risk Wilms tumor and other XPO1-dependent solid tumors; estimated enrollment ~45, with a Wilms-specific cohort and primary endpoint of overall response rate at 6 months. | Mittal et al., 2024, Commun Biol — https://doi.org/10.1038/s42003-024-06140-6; ClinicalTrials.gov NCT05985161 (2023) — https://clinicaltrials.gov/study/NCT05985161 | (mittal2024targetingtrip13in pages 2-3, NCT05985161 chunk 1, cantoni2026tumormicroenvironmentand pages 19-20) |
Table: This table summarizes major molecular mechanisms, genes, cellular processes, anatomic context, and recent evidence for Wilms tumor pathophysiology. It is useful as a compact knowledge-base style overview linking mechanistic biology to quantitative biomarkers and emerging therapeutic vulnerabilities.
Wilms tumor typically resembles fetal kidney and often contains a triphasic mixture of (i) blastema (undifferentiated metanephric mesenchyme), (ii) epithelial cells (prototubular/primitive tubules), and (iii) stromal elements (mesenchymal tissues). The blastemal compartment is often considered the aggressive and less-differentiated compartment and can be predominant in monophasic cases (neagu2025wilms’tumora pages 6-8, perotti2024hallmarkdiscoveriesin pages 6-10, tiburcio2024drosharegulatesmesenchymal pages 1-3).
Wilms tumors frequently arise within or adjacent to nephrogenic rests (embryonic renal precursor remnants) (perotti2024hallmarkdiscoveriesin pages 6-10, tiburcio2024drosharegulatesmesenchymal pages 1-3). Perotti et al. (Nature Reviews Urology; online 2023, issue Oct 2024) further highlight that intralobar nephrogenic rests (ILNR) and perilobar nephrogenic rests (PLNR) associate with distinct molecular subsets; PLNR is enriched in tumor subsets with dysregulated nephrogenic-zone self-renewal/differentiation programs (perotti2024hallmarkdiscoveriesin pages 25-29).
Perotti et al. explicitly define genomic imprinting as parent-specific monoallelic expression and describe Wilms tumor–predisposing lesions at 11p15 affecting imprint control regions for IGF2/H19 (perotti2024hallmarkdiscoveriesin pages 6-10, perotti2024hallmarkdiscoveriesin pages 10-14).
A major early and recurrent driver is abnormal imprinting/allelic imbalance at 11p15 (WT2 region), affecting IGF2 (growth factor) and H19. Perotti et al. report IGF2 overexpression in up to ~70% of sporadic tumors and its presence in nephrogenic rests, supporting an early lesion that precedes frank malignancy in many cases (perotti2024hallmarkdiscoveriesin pages 10-14).
Recent 2023–2024 developments (bilateral predisposition and mosaicism): Murphy et al. (Nature Communications, Dec 2023; https://doi.org/10.1038/s41467-023-43730-0) provide strong evidence that bilateral disease frequently reflects shared early 11p15.5 epigenetic/copy-number events rather than a shared tumor clone. Across 99 bilateral tumor specimens, they report 11p15.5 LOI (H19/ICR1 hypermethylation) in 58/99 (58.6%), 11p15.5 LOH in 25/99 (25.2%), and normal imprinting retention in 16/99 (16.1%) (murphy2023geneticandepigenetic pages 1-2). Synchronous paired tumors were concordant for 11p15.5 status in 29/30 (96.7%) yet usually lacked shared somatic variants, supporting independent tumor origins seeded by early predisposition events (murphy2023geneticandepigenetic pages 4-5).
In Beckwith–Wiedemann syndrome (BWS), Nirgude et al. (British Journal of Cancer, Dec 2024; https://doi.org/10.1038/s41416-023-02538-x) describe mosaic 11p15 LOH due to paternal uniparental isodisomy and note that LOH at 11p15 is present in at least 30% of Wilms tumors and is associated with higher staging (nirgude2024cancerpredispositionsignaling pages 1-2).
Cellular processes impacted: growth factor signaling, epigenetic regulation, cell proliferation and survival, and maintenance of embryonic progenitor programs (perotti2024hallmarkdiscoveriesin pages 10-14, nirgude2024cancerpredispositionsignaling pages 1-2).
WT1 is a master developmental regulator in kidney organogenesis. Perotti et al. summarize WT1’s role in mesenchymal–epithelial transitions and note that Wilms tumors often arise adjacent to nephrogenic rests, consistent with early developmental disruption (perotti2024hallmarkdiscoveriesin pages 6-10). Murphy et al. report that WT1 germline variants were among the most common detectable predispositions in their bilateral cohort (9/61, 14.8%) (murphy2023geneticandepigenetic pages 1-2).
A key mechanistic pattern in WT1-predisposed disease is a stereotyped evolutionary sequence in which early 11p events both (i) drive biallelic WT1 inactivation and (ii) activate the IGF2 imprinting domain, followed by WNT pathway activation. Murphy et al. report that in WT1-predisposed tumors, 11p15.5 LOH was present in all tumors (14/14) and CTNNB1 exon 3 activating mutations occurred in 10/14 (71.4%) of the WT1-associated set (murphy2023geneticandepigenetic pages 1-2).
Perotti et al. report CTNNB1 activating mutations in ~15% of Wilms tumors, with many affecting exon 3 to stabilize β-catenin and activate canonical WNT signaling. They also report a very strong association between WT1 and CTNNB1 mutations: 19/20 CTNNB1-mutant tumors also had WT1 mutations (p = 3.6 × 10−13) (perotti2024hallmarkdiscoveriesin pages 14-17). AMER1 (WTX) is described as part of the β-catenin destruction complex, with inactivation reported in up to ~30% in early screens (perotti2024hallmarkdiscoveriesin pages 14-17).
Clinical/biologic implication: this axis connects renal development programs to sustained progenitor proliferation and lineage mis-specification (perotti2024hallmarkdiscoveriesin pages 14-17).
A key modern concept is that a substantial subset of Wilms tumors are driven by disruption of miRNA biogenesis, which derepresses miRNA target programs controlling differentiation and proliferation.
Mechanistic primary evidence (2024): Tiburcio et al. (Molecular Cancer Research, Apr 2024; https://doi.org/10.1158/1541-7786.mcr-23-0930) show that DROSHA mutations correlate with derepression of miRNA target genes and a self-renewing mesenchymal state. They also connect miRNA loss to redox/lipid biology: miRNA-deficient Wilms tumor cells show aberrant redox metabolism and are sensitized to ferroptotic cell death through inhibition of GPX4, which detoxifies lipid peroxides (tiburcio2024drosharegulatesmesenchymal pages 1-3).
Perotti et al. report recurrent SIX1/SIX2 Q177R mutations in the homeodomain, frequent in blastemal tumors (18.1% of blastemal cases; 4.3% overall) and associated with a progenitor-like state and chemotherapy-resistant blastemal tumors (perotti2024hallmarkdiscoveriesin pages 17-21).
Perotti et al. describe MYCN gain/amplification and recurrent MYCN mutations (e.g., P44L), and specifically note that MYCN gain is associated with anaplastic histology and poor outcome (perotti2024hallmarkdiscoveriesin pages 14-17).
Perotti et al. report that diffuse anaplasia occurs in ~5–10% of Wilms tumors and that TP53 is mutated in ~50–60% of diffuse anaplastic Wilms tumors; they further note that TP53 immunopositivity is used as a surrogate for mutation and correlates with poor prognosis (perotti2024hallmarkdiscoveriesin pages 10-14).
Evidence in the retrieved corpus names drug-like agents (not formal CHEBI IDs): - Selinexor (KPT-330), an XPO1 inhibitor, tested in Wilms tumor (NCT05985161) (NCT05985161 chunk 1, cantoni2026tumormicroenvironmentand pages 19-20) - Tegavivint, described as a WNT/β-catenin inhibitor in pediatric trials (NCT04851119) (cantoni2026tumormicroenvironmentand pages 19-20) - Doxorubicin, used clinically and shown to synergize with nuclear export inhibition in a Wilms model system (mittal2024targetingtrip13in pages 2-3) - GPX4 inhibitors (e.g., discussed mechanistically as GPX4 inhibition) to induce ferroptosis in miRNA-deficient subset (tiburcio2024drosharegulatesmesenchymal pages 1-3)
The following disrupted processes are directly supported by the evidence base above: - Genomic imprinting / epigenetic regulation of gene expression (11p15.5; H19/ICR1 methylation) (perotti2024hallmarkdiscoveriesin pages 10-14, murphy2023geneticandepigenetic pages 1-2) - Regulation of growth factor signaling (IGF2 axis) (perotti2024hallmarkdiscoveriesin pages 10-14) - Kidney development / nephron progenitor differentiation; mesenchymal–epithelial transition (WT1, SIX programs; fetal kidney mapping) (perotti2024hallmarkdiscoveriesin pages 6-10, perotti2024hallmarkdiscoveriesin pages 25-29) - Canonical WNT signaling (β-catenin stabilization from CTNNB1 exon 3 mutations; AMER1/WTX disruption) (perotti2024hallmarkdiscoveriesin pages 14-17) - miRNA-mediated gene silencing / miRNA biogenesis (DROSHA/DGCR8/DICER1) (perotti2024hallmarkdiscoveriesin pages 17-21, murphy2023geneticandepigenetic pages 4-5) - Ferroptotic cell death / lipid peroxide detoxification (GPX4 dependence in miRNA-deficient state) (tiburcio2024drosharegulatesmesenchymal pages 1-3) - DNA damage response / apoptotic signaling (TP53 dysfunction in diffuse anaplasia) (perotti2024hallmarkdiscoveriesin pages 10-14) - Immune evasion / macrophage polarization (M2-skewed TAMs; immune-cold features) (cantoni2026tumormicroenvironmentand pages 6-7, rastegar2026understandinganaplasticwilmsa pages 38-42)
A mechanistically supported progression model (not necessarily universal across all patients) is: 1. Early developmental lesion in fetal kidney lineages leading to nephrogenic rests and/or clonal nephrogenesis (perotti2024hallmarkdiscoveriesin pages 6-10, perotti2024hallmarkdiscoveriesin pages 25-29). 2. Initiating epigenetic/copy-number event at 11p15.5 (LOI or LOH) resulting in increased IGF2 expression and altered imprinting balance; this is especially prominent in bilateral predisposition and BWS-associated cases (murphy2023geneticandepigenetic pages 1-2, nirgude2024cancerpredispositionsignaling pages 1-2). 3. Acquisition of additional driver mutations that enforce progenitor-like programs and proliferation: - WT1 inactivation and/or WNT activation (CTNNB1; AMER1/WTX) (perotti2024hallmarkdiscoveriesin pages 14-17, murphy2023geneticandepigenetic pages 1-2). - miRNA-processing loss (DROSHA/DGCR8/DICER1) causing widespread derepression of differentiation/proliferation programs and metabolic rewiring (tiburcio2024drosharegulatesmesenchymal pages 1-3, perotti2024hallmarkdiscoveriesin pages 17-21). - SIX1/SIX2 mutations sustaining nephron progenitor states and chemotherapy resistance in blastemal tumors (perotti2024hallmarkdiscoveriesin pages 17-21). 4. Progression to high-risk phenotypes via genomic instability and additional lesions: - TP53 disruption associated with diffuse anaplasia (5–10% of tumors; TP53 mutated ~50–60% in diffuse anaplasia) (perotti2024hallmarkdiscoveriesin pages 10-14). - Copy-number alterations including 1q gain and LOH 1p/16q, used for risk assessment and associated with relapse/poor outcome (cantoni2026tumormicroenvironmentand pages 2-4, mittal2024targetingtrip13in pages 2-3).
The following phenotype elements are supported conceptually and/or explicitly described in the retrieved evidence: - Renal neoplasm / embryonal tumor of kidney (disease entity) - Triphasic histology: blastemal, epithelial, stromal components; blastemal predominance as aggressive phenotype (neagu2025wilms’tumora pages 6-8, perotti2024hallmarkdiscoveriesin pages 6-10) - Nephrogenic rests (preneoplastic lesions), including ILNR/PLNR; association of PLNR with specific molecular subsets (perotti2024hallmarkdiscoveriesin pages 25-29, tiburcio2024drosharegulatesmesenchymal pages 1-3) - Diffuse anaplasia: nuclear enlargement/hyperchromasia and atypical multipolar mitoses; poor prognosis and TP53 association (perotti2024hallmarkdiscoveriesin pages 10-14, rastegar2026understandinganaplasticwilmsa pages 38-42)
Murphy et al. (Nature Communications, Dec 2023; https://doi.org/10.1038/s41467-023-43730-0) provide a modern framework in which bilateral disease is commonly driven by either detectable germline predisposition variants or post-zygotic mosaic imprinting defects at 11p15.5. Key statistics include LOI/LOH/ROI proportions across 99 tumors and high concordance of 11p15.5 status across synchronous tumors (murphy2023geneticandepigenetic pages 1-2, murphy2023geneticandepigenetic pages 4-5).
Tiburcio et al. (Molecular Cancer Research, Apr 2024; https://doi.org/10.1158/1541-7786.mcr-23-0930) move beyond association to mechanism by showing DROSHA-driven transcriptional programs and demonstrating a therapeutic vulnerability: miRNA-deficient Wilms cells are sensitized to ferroptosis through GPX4 inhibition (tiburcio2024drosharegulatesmesenchymal pages 1-3).
Perotti et al. (Nature Reviews Urology; Oct 2024 issue; https://doi.org/10.1038/s41585-023-00824-0) synthesize the field with key quantitative statements that directly support knowledge-base assertions, including (i) IGF2 overexpression up to ~70% of sporadic tumors, (ii) CTNNB1 frequency (~15%) and tight association with WT1, (iii) SIX1/2 Q177R enrichment in blastemal tumors, and (iv) TP53 mutation frequency (~50–60%) in diffuse anaplasia (perotti2024hallmarkdiscoveriesin pages 10-14, perotti2024hallmarkdiscoveriesin pages 14-17, perotti2024hallmarkdiscoveriesin pages 17-21).
Mittal et al. (Communications Biology, Apr 2024; https://doi.org/10.1038/s42003-024-06140-6) report clinically relevant genomic biomarkers in a small cohort (e.g., 1q gain, LOH 1p/16q) and identify XPO1 as a vulnerability, with nuclear export inhibitors synergizing with doxorubicin in vivo (mittal2024targetingtrip13in pages 2-3).
Evidence in the retrieved set supports several widely used stratification features: - Diffuse anaplasia and TP53: Diffuse anaplasia is a high-risk subtype (~5–10%); TP53 is mutated in ~50–60% of diffuse anaplastic tumors, and TP53 IHC is used as a surrogate associated with poor prognosis (perotti2024hallmarkdiscoveriesin pages 10-14). - 11p15 status: LOH/LOI at 11p15 is common; in BWS-associated analysis, 11p15 LOH is present in at least 30% of Wilms tumors and associated with higher staging (nirgude2024cancerpredispositionsignaling pages 1-2). - Copy-number biomarkers: combined LOH 1p/16q and 1q gain (20–30% overall) are adverse features; 1q gain is explicitly described as a poor prognostic factor in a 2024 cohort study (cantoni2026tumormicroenvironmentand pages 2-4, mittal2024targetingtrip13in pages 2-3).
Murphy et al. show that post-zygotic mosaic 11p15.5 LOI can be detectable in non-tumor tissues (adjacent kidney; sometimes peripheral blood), emphasizing the need for multi-tissue testing strategies when evaluating predisposition in bilateral disease (murphy2023geneticandepigenetic pages 7-9, murphy2023geneticandepigenetic pages 5-6).
From Perotti et al. (Nature Reviews Urology; Oct 2024 issue): - On origin: “Modern molecular findings support the embryonic renal origins of Wilms tumours.” (perotti2024hallmarkdiscoveriesin pages 21-25) - On tumor composition: Wilms tumors include “undifferentiated metanephric mesenchyme (blastema) and also more differentiated cells (stroma and tubular epithelial cells normally derived from metanephric mesenchyme)” (perotti2024hallmarkdiscoveriesin pages 21-25).
These statements support the mainstream interpretation that Wilms tumor pathophysiology is primarily a failure of normal renal differentiation programs, with recurrent lesions targeting developmental transcriptional/epigenetic and post-transcriptional (miRNA) regulators (perotti2024hallmarkdiscoveriesin pages 21-25, perotti2024hallmarkdiscoveriesin pages 17-21).
Wilms tumor arises when embryonic renal precursor cells (often within nephrogenic rests) experience early epigenetic/copy-number alterations—especially at 11p15.5—leading to dysregulated imprinting (IGF2 overexpression; H19 perturbation) and a growth-promoting, developmentally arrested state. Subsequent driver events (WT1 loss; CTNNB1/AMER1-mediated WNT activation; miRNA-processing defects; SIX1/SIX2 progenitor-program activation) reinforce progenitor self-renewal, impair differentiation, and remodel cellular metabolism. In a subset, additional genomic instability and TP53 defects drive diffuse anaplasia and therapy resistance. The tumor microenvironment is characterized by an inflammatory stromal compartment with M2-like macrophage dominance and generally low cytotoxic T-cell infiltration, contributing to immune evasion (perotti2024hallmarkdiscoveriesin pages 25-29, perotti2024hallmarkdiscoveriesin pages 10-14, perotti2024hallmarkdiscoveriesin pages 14-17, tiburcio2024drosharegulatesmesenchymal pages 1-3, cantoni2026tumormicroenvironmentand pages 6-7, rastegar2026understandinganaplasticwilmsa pages 38-42).
The retrieved evidence snippets did not include PubMed IDs explicitly for the 2023–2024 core sources; therefore, this report cites DOIs and ClinicalTrials.gov identifiers as stable primary references.
References
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(perotti2024hallmarkdiscoveriesin pages 6-10): Daniela Perotti, Richard D. Williams, Jenny Wegert, Jack Brzezinski, Mariana Maschietto, Sara Ciceri, David Gisselsson, Samantha Gadd, Amy L. Walz, Rhoikos Furtwaengler, Jarno Drost, Reem Al-Saadi, Nicholas Evageliou, Saskia L. Gooskens, Andrew L. Hong, Andrew J. Murphy, Michael V. Ortiz, Maureen J. O’Sullivan, Elizabeth A. Mullen, Marry M. van den Heuvel-Eibrink, Conrad V. Fernandez, Norbert Graf, Paul E. Grundy, James I. Geller, Jeffrey S. Dome, Elizabeth J. Perlman, Manfred Gessler, Vicki Huff, and Kathy Pritchard-Jones. Hallmark discoveries in the biology of wilms tumour. Nature reviews. Urology, 21:158-180, Oct 2024. URL: https://doi.org/10.1038/s41585-023-00824-0, doi:10.1038/s41585-023-00824-0. This article has 27 citations.
(tiburcio2024drosharegulatesmesenchymal pages 1-3): Patricia D.B. Tiburcio, Kavita Desai, Jiwoong Kim, Qinbo Zhou, Lei Guo, Xue Xiao, Li Zhou, Aysen Yuksel, Daniel R. Catchpoole, James F. Amatruda, Lin Xu, and Kenneth S. Chen. Drosha regulates mesenchymal gene expression in wilms tumor. Molecular cancer research : MCR, 22:711-720, Apr 2024. URL: https://doi.org/10.1158/1541-7786.mcr-23-0930, doi:10.1158/1541-7786.mcr-23-0930. This article has 9 citations.
(neagu2025wilms’tumora pages 6-8): Mihai Cristian Neagu, Vlad Laurenţiu David, Emil Radu Iacob, Sorin Dan Chiriac, Florin Lucian Muntean, and Eugen Sorin Boia. Wilms’ tumor: a review of clinical characteristics, treatment advances, and research opportunities. Medicina, 61:491, Mar 2025. URL: https://doi.org/10.3390/medicina61030491, doi:10.3390/medicina61030491. This article has 16 citations.
(perotti2024hallmarkdiscoveriesin pages 25-29): Daniela Perotti, Richard D. Williams, Jenny Wegert, Jack Brzezinski, Mariana Maschietto, Sara Ciceri, David Gisselsson, Samantha Gadd, Amy L. Walz, Rhoikos Furtwaengler, Jarno Drost, Reem Al-Saadi, Nicholas Evageliou, Saskia L. Gooskens, Andrew L. Hong, Andrew J. Murphy, Michael V. Ortiz, Maureen J. O’Sullivan, Elizabeth A. Mullen, Marry M. van den Heuvel-Eibrink, Conrad V. Fernandez, Norbert Graf, Paul E. Grundy, James I. Geller, Jeffrey S. Dome, Elizabeth J. Perlman, Manfred Gessler, Vicki Huff, and Kathy Pritchard-Jones. Hallmark discoveries in the biology of wilms tumour. Nature reviews. Urology, 21:158-180, Oct 2024. URL: https://doi.org/10.1038/s41585-023-00824-0, doi:10.1038/s41585-023-00824-0. This article has 27 citations.
(perotti2024hallmarkdiscoveriesin pages 10-14): Daniela Perotti, Richard D. Williams, Jenny Wegert, Jack Brzezinski, Mariana Maschietto, Sara Ciceri, David Gisselsson, Samantha Gadd, Amy L. Walz, Rhoikos Furtwaengler, Jarno Drost, Reem Al-Saadi, Nicholas Evageliou, Saskia L. Gooskens, Andrew L. Hong, Andrew J. Murphy, Michael V. Ortiz, Maureen J. O’Sullivan, Elizabeth A. Mullen, Marry M. van den Heuvel-Eibrink, Conrad V. Fernandez, Norbert Graf, Paul E. Grundy, James I. Geller, Jeffrey S. Dome, Elizabeth J. Perlman, Manfred Gessler, Vicki Huff, and Kathy Pritchard-Jones. Hallmark discoveries in the biology of wilms tumour. Nature reviews. Urology, 21:158-180, Oct 2024. URL: https://doi.org/10.1038/s41585-023-00824-0, doi:10.1038/s41585-023-00824-0. This article has 27 citations.
(perotti2024hallmarkdiscoveriesin pages 14-17): Daniela Perotti, Richard D. Williams, Jenny Wegert, Jack Brzezinski, Mariana Maschietto, Sara Ciceri, David Gisselsson, Samantha Gadd, Amy L. Walz, Rhoikos Furtwaengler, Jarno Drost, Reem Al-Saadi, Nicholas Evageliou, Saskia L. Gooskens, Andrew L. Hong, Andrew J. Murphy, Michael V. Ortiz, Maureen J. O’Sullivan, Elizabeth A. Mullen, Marry M. van den Heuvel-Eibrink, Conrad V. Fernandez, Norbert Graf, Paul E. Grundy, James I. Geller, Jeffrey S. Dome, Elizabeth J. Perlman, Manfred Gessler, Vicki Huff, and Kathy Pritchard-Jones. Hallmark discoveries in the biology of wilms tumour. Nature reviews. Urology, 21:158-180, Oct 2024. URL: https://doi.org/10.1038/s41585-023-00824-0, doi:10.1038/s41585-023-00824-0. This article has 27 citations.
(perotti2024hallmarkdiscoveriesin pages 17-21): Daniela Perotti, Richard D. Williams, Jenny Wegert, Jack Brzezinski, Mariana Maschietto, Sara Ciceri, David Gisselsson, Samantha Gadd, Amy L. Walz, Rhoikos Furtwaengler, Jarno Drost, Reem Al-Saadi, Nicholas Evageliou, Saskia L. Gooskens, Andrew L. Hong, Andrew J. Murphy, Michael V. Ortiz, Maureen J. O’Sullivan, Elizabeth A. Mullen, Marry M. van den Heuvel-Eibrink, Conrad V. Fernandez, Norbert Graf, Paul E. Grundy, James I. Geller, Jeffrey S. Dome, Elizabeth J. Perlman, Manfred Gessler, Vicki Huff, and Kathy Pritchard-Jones. Hallmark discoveries in the biology of wilms tumour. Nature reviews. Urology, 21:158-180, Oct 2024. URL: https://doi.org/10.1038/s41585-023-00824-0, doi:10.1038/s41585-023-00824-0. This article has 27 citations.
(cantoni2026tumormicroenvironmentand pages 2-4): Claudia Cantoni, Valerio Gaetano Vellone, Barbara Cafferata, Gabriele Gaggero, Martina Serra, Filippo Spreafico, Cristina Bottino, and Grazia Maria Spaggiari. Tumor microenvironment and immune response against wilms tumor: evasion mechanisms and implications for immunotherapeutic approaches. Cancers, 18:908, Mar 2026. URL: https://doi.org/10.3390/cancers18060908, doi:10.3390/cancers18060908. This article has 0 citations.
(murphy2023geneticandepigenetic pages 4-5): Andrew J. Murphy, Changde Cheng, Justin Williams, Timothy I. Shaw, Emilia M. Pinto, Karissa Dieseldorff-Jones, Jack Brzezinski, Lindsay A. Renfro, Brett Tornwall, Vicki Huff, Andrew L. Hong, Elizabeth A. Mullen, Brian Crompton, Jeffrey S. Dome, Conrad V. Fernandez, James I. Geller, Peter F. Ehrlich, Heather Mulder, Ninad Oak, Jamie Maciezsek, Carolyn M. Jablonowski, Andrew M. Fleming, Prahalathan Pichavaram, Christopher L. Morton, John Easton, Kim E. Nichols, Michael R. Clay, Teresa Santiago, Jinghui Zhang, Jun Yang, Gerard P. Zambetti, Zhaoming Wang, Andrew M. Davidoff, and Xiang Chen. Genetic and epigenetic features of bilateral wilms tumor predisposition in patients from the children’s oncology group aren18b5-q. Nature Communications, Dec 2023. URL: https://doi.org/10.1038/s41467-023-43730-0, doi:10.1038/s41467-023-43730-0. This article has 28 citations and is from a highest quality peer-reviewed journal.
(murphy2023geneticandepigenetic pages 1-2): Andrew J. Murphy, Changde Cheng, Justin Williams, Timothy I. Shaw, Emilia M. Pinto, Karissa Dieseldorff-Jones, Jack Brzezinski, Lindsay A. Renfro, Brett Tornwall, Vicki Huff, Andrew L. Hong, Elizabeth A. Mullen, Brian Crompton, Jeffrey S. Dome, Conrad V. Fernandez, James I. Geller, Peter F. Ehrlich, Heather Mulder, Ninad Oak, Jamie Maciezsek, Carolyn M. Jablonowski, Andrew M. Fleming, Prahalathan Pichavaram, Christopher L. Morton, John Easton, Kim E. Nichols, Michael R. Clay, Teresa Santiago, Jinghui Zhang, Jun Yang, Gerard P. Zambetti, Zhaoming Wang, Andrew M. Davidoff, and Xiang Chen. Genetic and epigenetic features of bilateral wilms tumor predisposition in patients from the children’s oncology group aren18b5-q. Nature Communications, Dec 2023. URL: https://doi.org/10.1038/s41467-023-43730-0, doi:10.1038/s41467-023-43730-0. This article has 28 citations and is from a highest quality peer-reviewed journal.
(nirgude2024cancerpredispositionsignaling pages 1-2): Snehal Nirgude, Natali S. Sobel Naveh, Sanam L. Kavari, Emily M. Traxler, and Jennifer M. Kalish. Cancer predisposition signaling in beckwith-wiedemann syndrome drives wilms tumor development. British Journal of Cancer, 130:638-650, Dec 2024. URL: https://doi.org/10.1038/s41416-023-02538-x, doi:10.1038/s41416-023-02538-x. This article has 9 citations and is from a domain leading peer-reviewed journal.
(murphy2023geneticandepigenetic pages 7-9): Andrew J. Murphy, Changde Cheng, Justin Williams, Timothy I. Shaw, Emilia M. Pinto, Karissa Dieseldorff-Jones, Jack Brzezinski, Lindsay A. Renfro, Brett Tornwall, Vicki Huff, Andrew L. Hong, Elizabeth A. Mullen, Brian Crompton, Jeffrey S. Dome, Conrad V. Fernandez, James I. Geller, Peter F. Ehrlich, Heather Mulder, Ninad Oak, Jamie Maciezsek, Carolyn M. Jablonowski, Andrew M. Fleming, Prahalathan Pichavaram, Christopher L. Morton, John Easton, Kim E. Nichols, Michael R. Clay, Teresa Santiago, Jinghui Zhang, Jun Yang, Gerard P. Zambetti, Zhaoming Wang, Andrew M. Davidoff, and Xiang Chen. Genetic and epigenetic features of bilateral wilms tumor predisposition in patients from the children’s oncology group aren18b5-q. Nature Communications, Dec 2023. URL: https://doi.org/10.1038/s41467-023-43730-0, doi:10.1038/s41467-023-43730-0. This article has 28 citations and is from a highest quality peer-reviewed journal.
(mittal2024targetingtrip13in pages 2-3): Karuna Mittal, Garrett W. Cooper, Benjamin P. Lee, Yongdong Su, Katie T. Skinner, Jenny Shim, Hunter C. Jonus, Won Jun Kim, Mihir Doshi, Diego Almanza, Bryan D. Kynnap, Amanda L. Christie, Xiaoping Yang, Glenn S. Cowley, Brittaney A. Leeper, Christopher L. Morton, Bhakti Dwivedi, Taylor Lawrence, Manali Rupji, Paula Keskula, Stephanie Meyer, Catherine M. Clinton, Manoj Bhasin, Brian D. Crompton, Yuen-Yi Tseng, Jesse S. Boehm, Keith L. Ligon, David E. Root, Andrew J. Murphy, David M. Weinstock, Prafulla C. Gokhale, Jennifer M. Spangle, Miguel N. Rivera, Elizabeth A. Mullen, Kimberly Stegmaier, Kelly C. Goldsmith, William C. Hahn, and Andrew L. Hong. Targeting trip13 in favorable histology wilms tumor with nuclear export inhibitors synergizes with doxorubicin. Communications Biology, Apr 2024. URL: https://doi.org/10.1038/s42003-024-06140-6, doi:10.1038/s42003-024-06140-6. This article has 6 citations and is from a peer-reviewed journal.
(lim2024interethnicvariationsin pages 15-17): Kia Teng Lim and Amos H. P. Loh. Inter-ethnic variations in the clinical, pathological, and molecular characteristics of wilms tumor. Cancers, 16:3051, Sep 2024. URL: https://doi.org/10.3390/cancers16173051, doi:10.3390/cancers16173051. This article has 6 citations.
(NCT05985161 chunk 1): A Study of Selinexor in People With Wilms Tumors and Other Solid Tumors. Memorial Sloan Kettering Cancer Center. 2023. ClinicalTrials.gov Identifier: NCT05985161
(cantoni2026tumormicroenvironmentand pages 19-20): Claudia Cantoni, Valerio Gaetano Vellone, Barbara Cafferata, Gabriele Gaggero, Martina Serra, Filippo Spreafico, Cristina Bottino, and Grazia Maria Spaggiari. Tumor microenvironment and immune response against wilms tumor: evasion mechanisms and implications for immunotherapeutic approaches. Cancers, 18:908, Mar 2026. URL: https://doi.org/10.3390/cancers18060908, doi:10.3390/cancers18060908. This article has 0 citations.
(perotti2024hallmarkdiscoveriesin pages 21-25): Daniela Perotti, Richard D. Williams, Jenny Wegert, Jack Brzezinski, Mariana Maschietto, Sara Ciceri, David Gisselsson, Samantha Gadd, Amy L. Walz, Rhoikos Furtwaengler, Jarno Drost, Reem Al-Saadi, Nicholas Evageliou, Saskia L. Gooskens, Andrew L. Hong, Andrew J. Murphy, Michael V. Ortiz, Maureen J. O’Sullivan, Elizabeth A. Mullen, Marry M. van den Heuvel-Eibrink, Conrad V. Fernandez, Norbert Graf, Paul E. Grundy, James I. Geller, Jeffrey S. Dome, Elizabeth J. Perlman, Manfred Gessler, Vicki Huff, and Kathy Pritchard-Jones. Hallmark discoveries in the biology of wilms tumour. Nature reviews. Urology, 21:158-180, Oct 2024. URL: https://doi.org/10.1038/s41585-023-00824-0, doi:10.1038/s41585-023-00824-0. This article has 27 citations.
(rastegar2026understandinganaplasticwilmsa pages 38-42): B Rastegar. Understanding anaplastic wilms tumors: spatial insights into their evolution and clinical significance. Unknown journal, 2026.
(murphy2023geneticandepigenetic pages 6-7): Andrew J. Murphy, Changde Cheng, Justin Williams, Timothy I. Shaw, Emilia M. Pinto, Karissa Dieseldorff-Jones, Jack Brzezinski, Lindsay A. Renfro, Brett Tornwall, Vicki Huff, Andrew L. Hong, Elizabeth A. Mullen, Brian Crompton, Jeffrey S. Dome, Conrad V. Fernandez, James I. Geller, Peter F. Ehrlich, Heather Mulder, Ninad Oak, Jamie Maciezsek, Carolyn M. Jablonowski, Andrew M. Fleming, Prahalathan Pichavaram, Christopher L. Morton, John Easton, Kim E. Nichols, Michael R. Clay, Teresa Santiago, Jinghui Zhang, Jun Yang, Gerard P. Zambetti, Zhaoming Wang, Andrew M. Davidoff, and Xiang Chen. Genetic and epigenetic features of bilateral wilms tumor predisposition in patients from the children’s oncology group aren18b5-q. Nature Communications, Dec 2023. URL: https://doi.org/10.1038/s41467-023-43730-0, doi:10.1038/s41467-023-43730-0. This article has 28 citations and is from a highest quality peer-reviewed journal.
(cantoni2026tumormicroenvironmentand pages 6-7): Claudia Cantoni, Valerio Gaetano Vellone, Barbara Cafferata, Gabriele Gaggero, Martina Serra, Filippo Spreafico, Cristina Bottino, and Grazia Maria Spaggiari. Tumor microenvironment and immune response against wilms tumor: evasion mechanisms and implications for immunotherapeutic approaches. Cancers, 18:908, Mar 2026. URL: https://doi.org/10.3390/cancers18060908, doi:10.3390/cancers18060908. This article has 0 citations.
(murphy2023geneticandepigenetic pages 5-6): Andrew J. Murphy, Changde Cheng, Justin Williams, Timothy I. Shaw, Emilia M. Pinto, Karissa Dieseldorff-Jones, Jack Brzezinski, Lindsay A. Renfro, Brett Tornwall, Vicki Huff, Andrew L. Hong, Elizabeth A. Mullen, Brian Crompton, Jeffrey S. Dome, Conrad V. Fernandez, James I. Geller, Peter F. Ehrlich, Heather Mulder, Ninad Oak, Jamie Maciezsek, Carolyn M. Jablonowski, Andrew M. Fleming, Prahalathan Pichavaram, Christopher L. Morton, John Easton, Kim E. Nichols, Michael R. Clay, Teresa Santiago, Jinghui Zhang, Jun Yang, Gerard P. Zambetti, Zhaoming Wang, Andrew M. Davidoff, and Xiang Chen. Genetic and epigenetic features of bilateral wilms tumor predisposition in patients from the children’s oncology group aren18b5-q. Nature Communications, Dec 2023. URL: https://doi.org/10.1038/s41467-023-43730-0, doi:10.1038/s41467-023-43730-0. This article has 28 citations and is from a highest quality peer-reviewed journal.