Welter, Nils;
Al-Saadi, Reem;
Gravier-Dumonceau, Robinson;
Furtwaengler, Rhoikos;
Graf, Norbert;
Wegert, Jenny;
Gessler, Manfred;
... Verschuur, Arnauld C; + view all
(2025)
The Clinical Impact of Somatic Copy Number Variations in Patients With Stage IV Wilms Tumor Enrolled in the SIOP 2001 Trial and Study.
Pediatric Blood & Cancer
, 72
(4)
, Article e31580. 10.1002/pbc.31580.
Preview |
PDF
The Clinical Impact of Somatic Copy Number Variations in Patients With Stage IV.pdf - Published Version Download (878kB) | Preview |
Abstract
Background: 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.
| Type: | Article |
|---|---|
| Title: | The Clinical Impact of Somatic Copy Number Variations in Patients With Stage IV Wilms Tumor Enrolled in the SIOP 2001 Trial and Study |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/pbc.31580 |
| Publisher version: | https://doi.org/10.1002/pbc.31580 |
| Language: | English |
| Additional information: | © 2025 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | copy number variations, outcome, preoperative chemotherapy, stage IV, Wilms tumor |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10211577 |
Archive Staff Only
 |
View Item |
