Welter Nils, Al-Saadi Reem, Gravier-Dumonceau Robinson, Furtwängler Rhoikos, Graf Norbert, Wegert Jenny, Gessler Manfred, Williams Richard D, Pritchard-Jones Kathy, Coulomb-L'Hermine Aurore, van den Heuvel-Eibrink Marry M, Verschuur Arnauld C
Department of Pediatric Oncology and Hematology, Saarland University, Homburg, Germany.
Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
Pediatr Blood Cancer. 2025 Apr;72(4):e31580. doi: 10.1002/pbc.31580. Epub 2025 Feb 3.
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.
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.
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).
We confirm the prognostic relevance of 1q+ and TP53 loss in stage IV WTs and emphasize their potential utility for future treatment stratification.
近期研究通过将体细胞基因组变异（如1号染色体长臂增益）与不良患者预后联系起来，阐明了分子生物学在肾母细胞瘤（WT）中的预后意义。本分析描述了IV期疾病WT患者肿瘤样本中拷贝数变异（CNV）的临床影响。
对参加SIOP 2001研究并接受术前化疗（pCHT）的来自英国、法国和德国的55例IV期疾病WT患者的肿瘤样本，使用多重连接依赖探针扩增（MLPA）检测其1号染色体长臂和其他感兴趣区域的CNV。分析所鉴定的CNV的预后影响。
1号染色体长臂增益（1q+）和TP53缺失分别发生在38.2%和16.4%的肿瘤中，与诊断时患者年龄较大相关（中位数[月]：分别为65和64，而每组无相应CNV的对照肿瘤为49，p分别为0.03和0.02），并且与5年无事件生存率较低相关（分别为40.0%和11.1%，而无相应CNV的对照肿瘤组为67.7%和82.6%，p分别为0.04和<0.01）。在仅发生肺转移的患者中，无论pCHT后有无转移灶切除术的缓解状态如何，1q+都是不良预后标志物。与无1q+的肿瘤相比，1q+的肿瘤中MYCN增益同时发生的频率更高（p = 0.03）。TP53缺失与高危组织学和较差的5年总生存率相关（p < 0.001）。
我们证实了1q+和TP53缺失在IV期WT中的预后相关性，并强调了它们在未来治疗分层中的潜在效用。
