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Personalised circulating tumour DNA assay with large-scale mutation coverage for sensitive minimal residual disease detection in colorectal cancer.
- Source :
- British Journal of Cancer; Aug2023, Vol. 129 Issue 2, p374-381, 8p
- Publication Year :
- 2023
-
Abstract
- Background: Postoperative minimal residual disease (MRD) detection using circulating-tumour DNA (ctDNA) requires a highly sensitive analysis platform. We have developed a tumour-informed, hybrid-capture ctDNA sequencing MRD assay. Methods: Personalised target-capture panels for ctDNA detection were designed using individual variants identified in tumour whole-exome sequencing of each patient. MRD status was determined using ultra-high-depth sequencing data of plasma cell-free DNA. The MRD positivity and its association with clinical outcome were analysed in Stage II or III colorectal cancer (CRC). Results: In 98 CRC patients, personalised panels for ctDNA sequencing were built from tumour data, including a median of 185 variants per patient. In silico simulation showed that increasing the number of target variants increases MRD detection sensitivity in low fractions (<0.01%). At postoperative 3-week, 21.4% of patients were positive for MRD by ctDNA. Postoperative positive MRD was strongly associated with poor disease-free survival (DFS) (adjusted hazard ratio 8.40, 95% confidence interval 3.49–20.2). Patients with a negative conversion of MRD after adjuvant therapy showed significantly better DFS (P < 0.001). Conclusion: Tumour-informed, hybrid-capture-based ctDNA assay monitoring a large number of patient-specific mutations is a sensitive strategy for MRD detection to predict recurrence in CRC. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00070920
- Volume :
- 129
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- British Journal of Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 164874665
- Full Text :
- https://doi.org/10.1038/s41416-023-02300-3