DNA methylation markers for sensitive detection of circulating tumor DNA in patients with gastroesophageal cancers
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Background
Patients with gastric and gastroesophageal junction adenocarcinomas (G-GEJ AC) face poor outcomes. Thus, sensitive biomarkers for improved clinical management are highly warranted. Detection of circulating tumor DNA (ctDNA) using DNA methylation biomarkers is a highly sensitive approach for cancer detection and management. Here, we explored the potential of a tumor-agnostic test targeting DNA methylation to detect ctDNA in patients with resectable and advanced G-GEJ AC.
Methods
Tumor DNA from 29 patients, and plasma cell-free DNA from 17 patients with advanced- and 17 patients with resectable G-GEJ AC, and from 50 healthy controls was analyzed. A tumor-agnostic, digital PCR test – TriMeth - targeting the gastrointestinal cancer-specific methylated genes C9orf50, KCNQ5 , and CLIP4 , was performed.
Results
TriMeth detected tumor DNA in 29/29 (100%) of the tumor tissue samples. Furthermore, TriMeth detected ctDNA in plasma from 13/17 (76%) of patients with advanced disease, 7/17 (41%) of patients with resectable disease, and in 0/50 (0%) of healthy controls.
Conclusions
This study demonstrates that TriMeth may hold potential as a biomarker for identification of ctDNA in patients with G-GEJ AC. The study sets the scene for ongoing larger clinical studies investigating the performance of TriMeth in different clinical settings.
