A DNA alteration and methylation co-detection method for clinical purpose

A DNA alteration and methylation co-detection method for clinical purpose

Abstract Traditional approaches for capturing genomic alterations and DNA methylation require separate assays, complicating clinical workflows and limiting sample utilization, particularly with low-input materials like cell-free DNA. To address these challenges, we introduce a streamlined approach c...

Full description

Saved in:
Bibliographic Details
Main Authors: Jiyan Yu, Chunhe Yang, Xintao Zhu, Zhankun Wang, Boping Xu, Ye Cai, Jingbo Zhao, Ruijian Guo, Wuzhou Yuan, Jianqing Wang, Bohao Dong, Frank Ron Zheng, Shuang Yang
Format: Article
Language:English
Published: Springer Nature 2025-06-01
Series:EMBO Molecular Medicine
Subjects:
Mutation
Methylation
Co-detection
Minimal Residual Disease
Companion Diagnostics
Online Access:https://doi.org/10.1038/s44321-025-00259-7
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Traditional approaches for capturing genomic alterations and DNA methylation require separate assays, complicating clinical workflows and limiting sample utilization, particularly with low-input materials like cell-free DNA. To address these challenges, we introduce a streamlined approach combining mutation and methylation profiling via mutation-protective strand synthesis with modified deoxycytidine triphosphates, demonstrating high concordance with standard enzymatic methyl-seq and DNA-seq in both whole-genome sequencing of cell lines and targeted sequencing of clinical samples. In potential clinical contexts, incorporating multi-omics information with this approach modestly improve circulating tumor DNA (ctDNA) detection by ~12% in pre-treatment lung cancer patients (N = 26) while preserving specificity in healthy controls (N = 13), and reveal relationships between homologous recombination repair (HRR) gene function and homologous recombination deficiency (HRD) mediated by promoter methylation-driven biallelic loss of HRR genes in gynecologic cancer patients (N = 27). For practical convenience, this method was also implemented on qPCR platform with high performance (0.5% limit of detection). With its adaptability and potential utility in ctDNA detection and treatment, this approach holds promise for advancing clinical diagnostics.
ISSN:1757-4684

Similar Items