Personalised circulating tumour DNA assay with large-scale mutation coverage for sensitive minimal residual disease detection in colorectal cancer

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 de...

Full description

Saved in:
Bibliographic Details
Published in:British journal of cancer 2023-08, Vol.129 (2), p.374-381
Main 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
Format: Article
Language:English
Subjects:
692/4028/67/1504/1885/1393
692/4028/67/1504/1885/1777
692/53/2422
Bioassays
Biomarkers, Tumor - genetics
Biomedical and Life Sciences
Biomedicine
Cancer Research
Circulating Tumor DNA - genetics
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - diagnosis
Colorectal Neoplasms - genetics
Deoxyribonucleic acid
Disease-Free Survival
DNA
Drug Resistance
Epidemiology
Humans
Minimal residual disease
Molecular Medicine
Mutation
Neoplasm, Residual - genetics
Oncology
Patients
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 (
ISSN:0007-0920
1532-1827
DOI:10.1038/s41416-023-02300-3