Synchronous bilateral Wilms tumors are prone to develop independently and respond differently to preoperative chemotherapy
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.
Authors
- Jinhu Wang (ORCID: https://orcid.org/0000-0002-7749-2475)
- Qiang Shu (ORCID: https://orcid.org/0000-0002-4106-6255)
- Manli Zhao (ORCID: https://orcid.org/0000-0002-7864-3853)
- Xuan Wu (ORCID: https://orcid.org/0000-0001-8539-6611)
- Meidan Ying (ORCID: https://orcid.org/0000-0003-0039-9683)
- Ting Tao (ORCID: https://orcid.org/0000-0003-1260-2351)
- Linjie Li (ORCID: https://orcid.org/0000-0003-4180-4614)
- Wan‐Xin Peng (ORCID: https://orcid.org/0000-0002-2551-8899)
- Jieni Xiong
- Xuan Jia (ORCID: https://orcid.org/0000-0001-8207-5716)
- Shuangai Liu
- Yong Li (ORCID: https://orcid.org/0000-0002-7063-408X)
- Xiang Zhang (ORCID: https://orcid.org/0000-0002-1277-4615)
- Chen Chen (ORCID: https://orcid.org/0000-0002-7957-0289)
- Yilong Wang (ORCID: https://orcid.org/0000-0002-7833-9990)
- Jiabin Cai (ORCID: https://orcid.org/0000-0002-2233-0022)
- Weizhong Gu (ORCID: https://orcid.org/0000-0002-3983-1413)
- Min He (ORCID: https://orcid.org/0000-0003-0178-097X)
- Junqing Mao
- Tao Li (ORCID: https://orcid.org/0009-0006-6811-2182)
- Can Lai
- Jinkai Peng (ORCID: https://orcid.org/0000-0003-2143-496X)
Institutions
- Xuzhou Medical College (CN)
- Zunyi Medical University (CN)
- Zhejiang Cancer Hospital (CN)
- Children's Hospital of Zhejiang University (CN)
- Zhejiang Lab (CN)
- Blood Center of Zhejiang Province (CN)
- Hunan Children's Hospital (CN)
- Xuzhou Children Hospital (CN)
- Second Affiliated Hospital of Nanjing Medical University (CN)
- Zhejiang University (CN)
Publication Details
- Journal
- International Journal of Cancer
- Published
- 2024-12-26
- DOI
- https://doi.org/10.1002/ijc.35297
- Citations
- 1
- Primary Topic
- Renal and related cancers
- Type
- article
- Field-Weighted Citation Impact
- 0.23
Funders
- National Natural Science Foundation of China