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- Title
Personalised circulating tumour DNA assay with large-scale mutation coverage for sensitive minimal residual disease detection in colorectal cancer.
- Authors
Ryoo, Seung-Bum; Heo, Sunghoon; Lim, Yoojoo; Lee, Wookjae; Cho, Su Han; Ahn, Jongseong; Kang, Jun-Kyu; Kim, Su Yeon; Kim, Hwang-Phill; Bang, Duhee; Kang, Sung-Bum; Yu, Chang Sik; Oh, Seong Taek; Park, Ji Won; Jeong, Seung-Yong; Kim, Young-Joon; Park, Kyu Joo; Han, Sae-Won; Kim, Tae-You
- 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.
- Publication
British Journal of Cancer, 2023, Vol 129, Issue 2, p374
- ISSN
0007-0920
- Publication type
Article
- DOI
10.1038/s41416-023-02300-3