Personalized and Tumor Informed Circulating Tumor DNA Assay for Molecular Residual Disease Monitoring of Solid Malignancies
Emerging evidence suggests that minimal residual disease (MRD) monitoring in solid tumors has implications for prognosis, treatment response, and therapeutic intervention. However, detecting MRD requires highly sensitive and specific circulating tumor DNA (ctDNA) assays. Therefore, we developed an innovative MRD monitoring assay that offers superior performance and cost advantage. Our approach utilizes a comprehensive genomic profiling panel to characterize the patient-specific mutational landscape of tumor tissue and selects up to 20 top-ranked variants to design a personalized panel, which is integrated with a tumor-naive cancer-type-specific fixed panel for ultra-deep sequencing of plasma ctDNA to monitor MRD in common solid tumors. Its limit of detection at the sample level reaches as low as 0.005%, with a specificity of 100%. Furthermore, when applied to colorectal, breast, and lung cancer patients, the ctDNA-MRD assay accurately predicted postoperative recurrence, prior to radiographic imaging by a median of 112 days for breast cancer and 83 days for lung cancer. In the tracked variants, clonal mutations demonstrated superior prognostic value compared to subclonal variants. This personalized MRD monitoring assay has the potential to enhance early detection of residual or recurrent disease, enable patient prognostic stratification, and inform clinical decision-making for patients with common solid tumors.
Authors
- Liang Cui (ORCID: https://orcid.org/0000-0002-5546-5097)
- Hongke Wang (ORCID: https://orcid.org/0009-0008-1773-367X)
- Qiuhua Deng (ORCID: https://orcid.org/0000-0002-7007-0392)
- WuQiang Cao (ORCID: https://orcid.org/0000-0002-6298-2623)
- Wei Gao (ORCID: https://orcid.org/0000-0003-3541-9568)
- Dingrong Zhong (ORCID: https://orcid.org/0000-0002-6229-1830)
- Xiaoying Zheng (ORCID: https://orcid.org/0000-0003-1966-044X)
- Liping Liu (ORCID: https://orcid.org/0000-0001-7017-301X)
- Wei Wang (ORCID: https://orcid.org/0000-0002-1356-7247)
- Liang Wang (ORCID: https://orcid.org/0000-0002-5247-6727)
- Chao Yang (ORCID: https://orcid.org/0000-0001-9276-5673)
- Han Liang (ORCID: https://orcid.org/0000-0002-5674-0994)
- Xin Yi (ORCID: https://orcid.org/0000-0003-4240-7039)
- Xinhua Du
- Liyan Huang (ORCID: https://orcid.org/0000-0002-2649-3312)
- Jun Huang (ORCID: https://orcid.org/0000-0003-4615-4411)
- Xuefeng Xia (ORCID: https://orcid.org/0000-0002-6390-1709)
- J Ma (ORCID: https://orcid.org/0000-0002-2058-431X)
- Yanfang Guan (ORCID: https://orcid.org/0000-0002-6722-2615)
- Xueliang Zeng
- Jianxing He
- Jing Bai (ORCID: https://orcid.org/0000-0002-3323-2946)
- Yan Zhang (ORCID: https://orcid.org/0000-0002-4835-8541)
Institutions
- Central South University (CN)
- Peking University (CN)
- National Institute of Biological Sciences, Beijing (CN)
- First Affiliated Hospital of Guangzhou Medical University (CN)
- Xi'an Jiaotong University (CN)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- MedComm
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1002/mco2.70483
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- National Science and Technology Major Project
- National Key Research and Development Program of China