ESMO Gastrointest Oncol. 2024 Dec;6
100104
N Øgaard,
C R Iden,
S Ø Jensen,
S M Mustafa,
E Aagaard,
J B Bramsen,
L B Ahlborn,
J P Hasselby,
K S Rohrberg,
M P Achiam,
C L Andersen,
M Mau-Sørensen.
Background: Patients with gastric and gastroesophageal junction adenocarcinomas (G-GEJ ACs) 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 ACs.
Material and methods: A tumor-agnostic digital PCR test-TriMeth-targeting the gastrointestinal cancer-specific methylated genes C9orf50, KCNQ5, and CLIP4 was carried out on a total of 131 study patients. DNA from surgical tumor specimens of 29 patients with G-GEJ ACs and plasma cell-free DNA from 52 patients with advanced and resectable G-GEJ ACs, and from 50 healthy controls, were analyzed.
Results: Methylated tumor DNA was detected by TriMeth in all of the surgical tumor specimens (29/29, 100%). Furthermore, TriMeth detected ctDNA in plasma from 31/52 (60%) patients with G-GEJ AC, including in 13/17 (76%) advanced cases, and 18/35 (51%) resectable cases. ctDNA was not detected in healthy controls (0/50, 0%).
Conclusions: This study demonstrates that TriMeth may hold potential as a biomarker for identifying ctDNA in patients with G-GEJ ACs. The study sets the scene for ongoing larger clinical studies investigating the performance of TriMeth in different clinical settings.
Keywords: DNA methylation; cancer biomarker; circulating tumor DNA; esophagus adenocarcinoma; gastric adenocarcinoma; gastroesophageal junction cancer