TY - JOUR
T1 - The pathophysiology of bilateral and multifocal Wilms tumors
T2 - What we can learn from the study of predisposition syndromes
AU - Welter, Nils
AU - Brzezinski, Jack
AU - Treece, Amy
AU - Chintagumpala, Murali
AU - Young, Matthew D
AU - Perotti, Daniela
AU - Kieran, Kathleen
AU - Jongmans, Marjolijn C J
AU - Murphy, Andrew J
N1 - Funding Information:
The authors wish to thank the collaborative environment provided by the COG-SIOP-HARMONICA initiative for the opportunity to participate in this review.
Publisher Copyright:
© 2022 Wiley Periodicals LLC.
PY - 2023/5
Y1 - 2023/5
N2 - Approximately 5% of patients with Wilms tumor present with synchronous bilateral disease. The development of synchronous bilateral Wilms tumor (BWT) is highly suggestive of a genetic or epigenetic predisposition. Patients with known germline predisposition to Wilms tumor (WT1 variants, Beckwith Wiedemann spectrum, TRIM28 variants) have a higher incidence of BWT. This Children's Oncology Group (COG)-International Society for Pediatric Oncology (SIOP-) HARMONICA initiative review for pediatric renal tumors details germline genetic and epigenetic predisposition to BWT development, with an emphasis on alterations in 11p15.5 (ICR1 gain of methylation, paternal uniparental disomy, and postzygotic somatic mosaicism), WT1, TRIM28, and REST. Molecular mechanisms that result in BWT are often also present in multifocal Wilms tumor (multiple separate tumors in one or both kidneys). We identify priority areas for international collaborative research to better understand how predisposing genetic or epigenetic factors associate with response to neoadjuvant chemotherapy, oncologic outcomes, and long-term renal function outcomes.
AB - Approximately 5% of patients with Wilms tumor present with synchronous bilateral disease. The development of synchronous bilateral Wilms tumor (BWT) is highly suggestive of a genetic or epigenetic predisposition. Patients with known germline predisposition to Wilms tumor (WT1 variants, Beckwith Wiedemann spectrum, TRIM28 variants) have a higher incidence of BWT. This Children's Oncology Group (COG)-International Society for Pediatric Oncology (SIOP-) HARMONICA initiative review for pediatric renal tumors details germline genetic and epigenetic predisposition to BWT development, with an emphasis on alterations in 11p15.5 (ICR1 gain of methylation, paternal uniparental disomy, and postzygotic somatic mosaicism), WT1, TRIM28, and REST. Molecular mechanisms that result in BWT are often also present in multifocal Wilms tumor (multiple separate tumors in one or both kidneys). We identify priority areas for international collaborative research to better understand how predisposing genetic or epigenetic factors associate with response to neoadjuvant chemotherapy, oncologic outcomes, and long-term renal function outcomes.
KW - 11p15.5
KW - bilateral Wilms tumor
KW - genetic predisposition
KW - mosaicism
KW - TRIM28
KW - WT1
UR - http://www.scopus.com/inward/record.url?scp=85137919636&partnerID=8YFLogxK
U2 - 10.1002/pbc.29984
DO - 10.1002/pbc.29984
M3 - Review article
C2 - 36094328
SN - 1545-5009
VL - 70 Suppl 2
JO - Pediatric Blood & Cancer
JF - Pediatric Blood & Cancer
IS - S2
M1 - e29984
ER -