The Clinical Impact of Somatic Copy Number Variations in Patients With Stage IV Wilms Tumor Enrolled in the SIOP 2001 Trial and Study

IF 2.4 3区医学 Q2 HEMATOLOGY

Pediatric Blood & Cancer Pub Date : 2025-02-03 DOI:10.1002/pbc.31580

Nils Welter, Reem Al-Saadi, Robinson Gravier-Dumonceau, Rhoikos Furtwängler, Norbert Graf, Jenny Wegert, Manfred Gessler, Richard D. Williams, Kathy Pritchard-Jones, Aurore Coulomb-L'Hermine, Marry M. van den Heuvel-Eibrink, Arnauld C. Verschuur

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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.

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来源期刊

Pediatric Blood & Cancer 医学-小儿科

CiteScore

4.90

自引率

9.40%

发文量

546

审稿时长

1.5 months

期刊介绍： Pediatric Blood & Cancer publishes the highest quality manuscripts describing basic and clinical investigations of blood disorders and malignant diseases of childhood including diagnosis, treatment, epidemiology, etiology, biology, and molecular and clinical genetics of these diseases as they affect children, adolescents, and young adults. Pediatric Blood & Cancer will also include studies on such treatment options as hematopoietic stem cell transplantation, immunology, and gene therapy.