Tao Ting, Liu Shuangai, He Min, Zhao Manli, Chen Chen, Peng Jinkai, Wang Yilong, Cai Jiabin, Xiong Jieni, Lai Can, Gu Weizhong, Ying Meidan, Mao Junqing, Li Linjie, Jia Xuan, Wu Xuan, Peng Wanxin, Zhang Xiang, Li Yong, Li Tao, Wang Jinhu, Shu Qiang
Pediatric Cancer Research Center, National Clinical Research Center for Child Health, Children's Hospital Zhejiang University School of Medicine, Hangzhou, China.
Department of Surgical Oncology, Children's Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
Int J Cancer. 2025 May 1;156(9):1746-1755. doi: 10.1002/ijc.35297. Epub 2024 Dec 26.
Wilms tumor (WT) is the most common kidney cancer in infants and young children. The determination of the clonality of bilateral WTs is critical to the treatment, because lineage-independent and metastatic tumors may require different treatment strategies. Here we found synchronous bilateral WT (n = 24 tumors from 12 patients) responded differently to preoperative chemotherapy. Transcriptome, whole-exome and whole-genome analysis (n = 12 tumors from 6 patients) demonstrated that each side of bilateral WT was clonally independent in terms of somatic driver mutations, copy number variations and transcriptomic profile. Molecular timing analysis revealed distinct timing and patterns of chromosomal evolution and mutational processes between the two sides of WT. Mutations in WT1, CTNNB1 and copy-neutral loss of heterozygosity of 11p15.5 provide possible genetic predisposition for the early initiation of bilateral WT. Our results provide comprehensive evidence and new insights regarding the separate initiation and early embryonic development of bilateral WT, which may benefit clinical practices in treating metastatic or refractory bilateral WT.
肾母细胞瘤（WT）是婴幼儿中最常见的肾癌。确定双侧WT的克隆性对治疗至关重要，因为不依赖谱系和转移性肿瘤可能需要不同的治疗策略。在此，我们发现同步双侧WT（来自12例患者的24个肿瘤）对术前化疗反应不同。转录组、全外显子组和全基因组分析（来自6例患者的12个肿瘤）表明，双侧WT的每一侧在体细胞驱动突变、拷贝数变异和转录组谱方面都是克隆独立的。分子时间分析揭示了WT两侧染色体进化和突变过程的不同时间和模式。WT1、CTNNB1的突变以及11p15.5的拷贝中性杂合性缺失为双侧WT的早期发生提供了可能的遗传易感性。我们的结果为双侧WT的独立起始和早期胚胎发育提供了全面的证据和新见解，这可能有益于治疗转移性或难治性双侧WT的临床实践。
