Wilms tumor (WT), the most prevalent type of renal cancer in children, exhibits overall survival rates exceeding 90%. However, chemotherapy resistance, which occurs in approximately 10% of WT cases, is a major challenge for the treatment of WT, particularly for advanced-stage patients. In this study, we aimed to discover potential mutation markers and drug targets associated with chemotherapy resistance in advanced-stage WT. We performed exome sequencing to detect somatic mutations and molecular targets in 43 WT samples, comprising 26 advanced-stage WTs, of which 7 cases were chemotherapy-resistant. Our analysis revealed four genes (ALPK2,C16orf96,PRKDC, andSVIL) that correlated with chemotherapy resistance and reduced disease-free survival in advanced-stage WT. Additionally, we identified driver mutations in 55 genes within the chemotherapy-resistant group, including 14 druggable cancer driver genes. Based on the mutation profiles of the resistant WT samples, we propose potential therapeutic strategies involving platinum-based agents, PARP inhibitors, and antibiotic/antineoplastic agents. Our findings provide insights into the genetic landscape of WT and offer potential avenues for targeted treatment, particularly for patients with chemotherapy resistance.
肾母细胞瘤（Wilms tumor, WT）作为儿童中最常见的肾脏恶性肿瘤，其总体生存率已超过90%。然而，约10%的WT病例会出现化疗耐药，这成为WT治疗尤其是晚期患者面临的主要挑战。本研究旨在探索与晚期WT化疗耐药相关的潜在突变标志物及药物靶点。我们对43例WT样本（包括26例晚期WT，其中7例为化疗耐药病例）进行了外显子组测序，以检测体细胞突变及分子靶点。分析结果显示，ALPK2、C16orf96、PRKDC和SVIL这四个基因与晚期WT的化疗耐药及无病生存期缩短相关。此外，我们在化疗耐药组中鉴定出55个基因存在驱动突变，其中包括14个可成药的癌症驱动基因。基于耐药WT样本的突变谱，我们提出了包含铂类药物、PARP抑制剂以及抗生素/抗肿瘤药物在内的潜在治疗策略。本研究结果揭示了WT的遗传学特征，并为靶向治疗——特别是针对化疗耐药患者——提供了潜在途径。
肿瘤(癌症)患者之家