Welter, NilsNilsWelterAl-Saadi, ReemReemAl-SaadiGravier-Dumonceau, RobinsonRobinsonGravier-DumonceauFurtwängler, RhoikosRhoikosFurtwänglerGraf, NorbertNorbertGrafWegert, JennyJennyWegertGessler, ManfredManfredGesslerWilliams, Richard DRichard DWilliamsPritchard-Jones, KathyKathyPritchard-JonesCoulomb-L'Hermine, AuroreAuroreCoulomb-L'Herminevan den Heuvel-Eibrink, Marry MMarry Mvan den Heuvel-EibrinkVerschuur, Arnauld CArnauld CVerschuur2025-03-132025-03-132025-04https://boris-portal.unibe.ch/handle/20.500.12422/204720Background Recent research elucidated the prognostic significance of molecular biology in Wilms tumor (WT) by linking somatic genomic variants (such as gain of chromosome 1q) to unfavorable patient outcomes. This analysis describes the clinical impact of copy number variations (CNV) in tumor samples of WT patients with stage IV disease. Methods Tumor samples of 55 WT patients with stage IV disease from the United Kingdom, France, and Germany enrolled in the SIOP 2001 study and treated with preoperative chemotherapy (pCHT) were examined for their CNVs of chromosome 1q and other regions of interest using multiplex ligation-dependent probe amplification (MLPA). The identified CNV were analyzed regarding their prognostic impact. Results Chromosome 1q gain (1q+) and TP53 loss occurred in 38.2% and 16.4% of tumors and were associated with older patient age at diagnosis (median [months]: 65 and 64 vs. 49 each, p = 0.03 and 0.02, respectively) and poorer 5-year event-free survival (40.0% and 11.1% vs. 67.7% and 82.6%, p = 0.04 and <0.01, respectively) compared to their specific control group of tumors without the respective CNV. In patients with pulmonary-only metastasis, 1q+ was an adverse prognostic marker irrespective of remission status after pCHT with or without metastasectomy. A simultaneous MYCN gain occurred more frequently in tumors with 1q+ than in tumors without 1q+ (p = 0.03). TP53 loss was linked to high-risk histology and inferior 5-year overall survival (p < 0.001). Conclusions We confirm the prognostic relevance of 1q+ and TP53 loss in stage IV WTs and emphasize their potential utility for future treatment stratification.enWilms tumorcopy number variationsoutcomepreoperative chemotherapystage IV600 - Technology::610 - Medicine & healthThe Clinical Impact of Somatic Copy Number Variations in Patients with Stage IV Wilms Tumor Enrolled in the SIOP 2001 Trial and Study.article10.48620/859373989548410.1002/pbc.31580