TY - JOUR
T1 - Systematic Review
T2 - Prognostic Molecular Biomarkers in Wilms Tumors
AU - Oller, Agustina
AU - Kemmeren, Patrick
AU - Perotti, Daniela
AU - van Tinteren, Harm
AU - Verschuur, Arnauld
AU - Spreafico, Filippo
AU - Brok, Jesper
AU - Furtwängler, Rhoikos C.J.
AU - Chowdhury, Tanzina
AU - Al-Saadi, Reem
AU - Vujanic, Gordan M.
AU - Treece, Amy L.
AU - Drost, Jarno
AU - van Grotel, Martine
AU - Mullen, Elizabeth A.
AU - Evageliou, Nicholas F.
AU - Graf, Norbert
AU - Hong, Andrew L.
AU - Gessler, Manfred
AU - Geller, James I.
AU - van den Heuvel-Eibrink, Marry M.
N1 - Publisher Copyright:
© 2026 by American Society of Clinical Oncology
PY - 2026/5
Y1 - 2026/5
N2 - PURPOSE – Molecular biomarkers are increasingly used for risk stratification, particularly in up-front surgery settings (Children's Oncology Group trials), whereas in preoperative chemotherapy setting, the ongoing International Society of Pediatric Oncology (SIOP)-Renal Tumor Study Group-2016 UMBRELLA study aims to validate selected biomarkers for future risk-adapted treatment strategies. This systematic review summarizes all literature on the prognostic value of these biomarkers.MATERIALS AND METHODS – A systematic literature review (PubMed and Embase; up to January 2025) included studies with ≥50 de novo Wilms tumors (WTs). Eligible biomarkers included copy number variations; 1q gain, 1p and/or 16q loss of heterozygosity (LOH)/loss, 12 gain, 14q loss, 22 loss, 11p15 LOH/loss of imprinting (LOI), and structural somatic variants (TP53 [and/or 17p loss], MYCN, FBXW7, WT1, WTX, SIX1/SIX2, DROSHA, DGCR8, AMER1, CTNNB1, GPC3, MLLT1, DICER1, DIS3L2). Outcome included relapse-free survival, event-free survival (EFS), and overall survival (OS). Risk of bias was assessed with quality in prognosis studies tool.RESULTS – Low-bias multivariable/stratified analyses identified 1q gain as worse EFS and 1p and/or 16q LOH/loss as worse EFS/OS prognostic factors, in up-front nephrectomy settings. Preoperative chemotherapy settings revealed similar trends with lacking significance. TP53 and MYCN were adverse prognostic in univariate analyses. No prognostic data were available for the remaining variants.CONCLUSION – 1q gain and 1p and/or 16q LOH/loss emerge as independent prognostic biomarkers in up-front nephrectomy settings. Evidence remains limited in preoperative chemotherapy settings, particularly when using SIOP-oriented treatment algorithms. Prognostic value of TP53, MYCN, and 11p15 LOH/LOI warrants further validation in both settings. This highlights the need for adequately powered prospective studies, specifically in the preoperative chemotherapy setting, to establish reliable molecular biomarkers.
AB - PURPOSE – Molecular biomarkers are increasingly used for risk stratification, particularly in up-front surgery settings (Children's Oncology Group trials), whereas in preoperative chemotherapy setting, the ongoing International Society of Pediatric Oncology (SIOP)-Renal Tumor Study Group-2016 UMBRELLA study aims to validate selected biomarkers for future risk-adapted treatment strategies. This systematic review summarizes all literature on the prognostic value of these biomarkers.MATERIALS AND METHODS – A systematic literature review (PubMed and Embase; up to January 2025) included studies with ≥50 de novo Wilms tumors (WTs). Eligible biomarkers included copy number variations; 1q gain, 1p and/or 16q loss of heterozygosity (LOH)/loss, 12 gain, 14q loss, 22 loss, 11p15 LOH/loss of imprinting (LOI), and structural somatic variants (TP53 [and/or 17p loss], MYCN, FBXW7, WT1, WTX, SIX1/SIX2, DROSHA, DGCR8, AMER1, CTNNB1, GPC3, MLLT1, DICER1, DIS3L2). Outcome included relapse-free survival, event-free survival (EFS), and overall survival (OS). Risk of bias was assessed with quality in prognosis studies tool.RESULTS – Low-bias multivariable/stratified analyses identified 1q gain as worse EFS and 1p and/or 16q LOH/loss as worse EFS/OS prognostic factors, in up-front nephrectomy settings. Preoperative chemotherapy settings revealed similar trends with lacking significance. TP53 and MYCN were adverse prognostic in univariate analyses. No prognostic data were available for the remaining variants.CONCLUSION – 1q gain and 1p and/or 16q LOH/loss emerge as independent prognostic biomarkers in up-front nephrectomy settings. Evidence remains limited in preoperative chemotherapy settings, particularly when using SIOP-oriented treatment algorithms. Prognostic value of TP53, MYCN, and 11p15 LOH/LOI warrants further validation in both settings. This highlights the need for adequately powered prospective studies, specifically in the preoperative chemotherapy setting, to establish reliable molecular biomarkers.
UR - https://www.scopus.com/pages/publications/105043460283
U2 - 10.1200/PO-25-01017
DO - 10.1200/PO-25-01017
M3 - Review
C2 - 42150146
AN - SCOPUS:105043460283
SN - 2473-4284
VL - 10
SP - 1
EP - 17
JO - JCO Precision Oncology
JF - JCO Precision Oncology
IS - 5
ER -