Identification of multiple genomic alterations and prediction of neoantigens from circulating tumor cells at the single-cell level
Circulating tumor cells (CTCs) are linked to cancer progression and poor prognosis, offering valuable genetic insights into tumors. Accurate detection of genomic alterations in CTCs is essential for improving cancer diagnosis and treatment. To address this, we develop Uniform Chromosome Conformation Capture (Uni-C), a method for profiling 3D chromatin architecture and genomic alterations at the single-cell level. Using Uni-C, we analyze CTCs from pancreatic cancer patient-derived xenograft (PDX) and spontaneous tumor mouse models. In the PDX model, integrating data from seven CTCs captures 88.7% of SNPs and INDELs, and 75.0% of structural variants present in tumor tissue. These findings indicate that variants detected in CTCs reflect tumor genomic features. Notably, we observe chromatin conformation differences between mitotic and interphase CTCs, suggesting potential markers of cell vitality. In the spontaneous tumor model, we identify driver gene mutations in CTCs and predict neoantigens, advancing early cancer detection and treatment strategies.
Authors
- Jiling Feng (ORCID: https://orcid.org/0000-0001-5581-0623)
- Taiyu Zhang
- Yu Guo (ORCID: https://orcid.org/0000-0002-8109-7515)
- Chengchao Wu
- Xiaochen Gao (ORCID: https://orcid.org/0009-0001-0245-9478)
- Da Lin (ORCID: https://orcid.org/0000-0003-0585-821X)
- Jiajia Wang (ORCID: https://orcid.org/0009-0003-9470-6222)
- Xinyu Li (ORCID: https://orcid.org/0000-0001-7175-7332)
- Weihao Wang (ORCID: https://orcid.org/0000-0001-9897-1144)
- Yuqin Yang (ORCID: https://orcid.org/0000-0002-8651-7072)
- Weize Xu (ORCID: https://orcid.org/0000-0002-3903-0683)
- Qianqian Guo
- Ming Jiao
Institutions
- Guangdong Medical College (CN)
- Shanghai Jiao Tong University (CN)
- Dalian Medical University (CN)
- Huazhong Agricultural University (CN)
- Guangzhou Institutes of Biomedicine and Health (CN)
- Shanghai Mental Health Center (CN)
- Fudan University Shanghai Cancer Center (CN)
- Shanghai First People's Hospital (CN)
- Shanghai Clinical Research Center (CN)
- Affiliated Hospital of Guangdong Medical College Hospital (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-07-26
- DOI
- https://doi.org/10.1038/s41467-025-62215-w
- Citations
- 1
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 0.94
Funders
- National Natural Science Foundation of China
- Soongsil University
- Science and Technology Planning Project of Guangdong Province