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- Title
Mutation-Agnostic Detection of Colorectal Cancer Using Liquid Biopsy-Based Methylation-Specific Signatures.
- Authors
Gouda, Mohamed A; Duose, Dzifa Y; Lapin, Morten; Zalles, Stephanie; Huang, Helen J; Xi, Yuanxin; Zheng, Xiaofeng; Aldesoky, Amira I; Alhanafy, Alshimaa M; Shehata, Mohamed A; Wang, Jing; Kopetz, Scott; Meric-Bernstam, Funda; Wistuba, Ignacio I; Luthra, Rajyalakshmi; Janku, Filip
- Abstract
Detection of methylation patterns in circulating tumor DNA (ctDNA) can offer a novel approach for cancer diagnostics given the unique signature for each tumor type. We developed a next-generation sequencing (NGS)-based assay targeting 32 CpG sites to detect colorectal cancer-specific ctDNA. NGS was performed on bisulfite-converted libraries and status dichotomization was done using median methylation ratios at all targets. We included plasma samples from patients with metastatic colorectal (n = 20) and non-colorectal cancers (n = 8); and healthy volunteers (n = 4). Median methylation ratio was higher in colorectal cancer compared with non-colorectal cancers (P = .001) and normal donors (P = .005). The assay detected ctDNA in 85% of patients with colorectal cancer at a specificity of 92%. Notably, we were able to detect methylated ctDNA in 75% of patients in whom ctDNA was not detected by other methods. Detection of methylated ctDNA was associated with shorter median progression-free survival compared to non-detection (8 weeks versus 54 weeks; P = .027).
- Subjects
METASTASIS; COLORECTAL cancer; CANCER patients; DNA methylation; GENE expression profiling; METHYLATION; DESCRIPTIVE statistics; RESEARCH funding; BODY fluid examination; PROGRESSION-free survival
- Publication
Oncologist, 2023, Vol 28, Issue 4, p368
- ISSN
1083-7159
- Publication type
Article
- DOI
10.1093/oncolo/oyac204