TY - JOUR
T1 - DNA methylation markers for sensitive detection of circulating tumor DNA in patients with gastroesophageal cancers
AU - Øgaard, N.
AU - Iden, C.R.
AU - Jensen, S.Ø.
AU - Mustafa, S.M.
AU - Aagaard, E.
AU - Bramsen, J.B.
AU - Ahlborn, L.B.
AU - Hasselby, J.P.
AU - Rohrberg, K.S.
AU - Achiam, M.P.
AU - Andersen, C.L.
AU - Mau-Sørensen, M.
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
KW - cancer biomarker
KW - circulating tumor DNA
KW - DNA methylation
KW - esophagus adenocarcinoma
KW - gastric adenocarcinoma
KW - gastroesophageal junction cancer
UR - https://www.scopus.com/pages/publications/105010881276
U2 - 10.1016/j.esmogo.2024.100104
DO - 10.1016/j.esmogo.2024.100104
M3 - Journal article
AN - SCOPUS:105010881276
SN - 2949-8198
VL - 6
JO - ESMO Gastrointestinal Oncology
JF - ESMO Gastrointestinal Oncology
M1 - 100104
ER -