DNA methylation markers for sensitive detection of circulating tumor DNA in patients with gastroesophageal cancers
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-12-01
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| Series: | ESMO Gastrointestinal Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2949819824000657 |
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| author | 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 |
| author_facet | 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 |
| author_sort | N. Øgaard |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7e5c51e4cdb041eb8bdf336140bcffb3 |
| institution | Kabale University |
| issn | 2949-8198 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | ESMO Gastrointestinal Oncology |
| spelling | doaj-art-7e5c51e4cdb041eb8bdf336140bcffb32024-12-17T05:02:28ZengElsevierESMO Gastrointestinal Oncology2949-81982024-12-016100104DNA methylation markers for sensitive detection of circulating tumor DNA in patients with gastroesophageal cancersN. Øgaard0C.R. Iden1S.Ø. Jensen2S.M. Mustafa3E. Aagaard4J.B. Bramsen5L.B. Ahlborn6J.P. Hasselby7K.S. Rohrberg8M.P. Achiam9C.L. Andersen10M. Mau-Sørensen11Department of Molecular Medicine, Aarhus University Hospital, Aarhus, DenmarkDepartment of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, DenmarkDepartment of Molecular Medicine, Aarhus University Hospital, Aarhus, DenmarkDepartment of Molecular Medicine, Aarhus University Hospital, Aarhus, DenmarkDepartment of Molecular Medicine, Aarhus University Hospital, Aarhus, DenmarkDepartment of Molecular Medicine, Aarhus University Hospital, Aarhus, DenmarkDepartment of Genomic Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, DenmarkDepartment of Pathology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, DenmarkDepartment of Oncology, Phase 1 Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, DenmarkDepartment of Surgery and Transplantation, Copenhagen University Hospital, Rigshospitalet, Copenhagen, DenmarkDepartment of Molecular Medicine, Aarhus University Hospital, Aarhus, DenmarkDepartment of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Correspondence to: Dr Morten Mau-Sørensen, Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Tel: +45 3545 5012Background: 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.http://www.sciencedirect.com/science/article/pii/S2949819824000657esophagus adenocarcinomagastric adenocarcinomagastroesophageal junction cancerDNA methylationcirculating tumor DNAcancer biomarker |
| spellingShingle | 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 DNA methylation markers for sensitive detection of circulating tumor DNA in patients with gastroesophageal cancers ESMO Gastrointestinal Oncology esophagus adenocarcinoma gastric adenocarcinoma gastroesophageal junction cancer DNA methylation circulating tumor DNA cancer biomarker |
| title | DNA methylation markers for sensitive detection of circulating tumor DNA in patients with gastroesophageal cancers |
| title_full | DNA methylation markers for sensitive detection of circulating tumor DNA in patients with gastroesophageal cancers |
| title_fullStr | DNA methylation markers for sensitive detection of circulating tumor DNA in patients with gastroesophageal cancers |
| title_full_unstemmed | DNA methylation markers for sensitive detection of circulating tumor DNA in patients with gastroesophageal cancers |
| title_short | DNA methylation markers for sensitive detection of circulating tumor DNA in patients with gastroesophageal cancers |
| title_sort | dna methylation markers for sensitive detection of circulating tumor dna in patients with gastroesophageal cancers |
| topic | esophagus adenocarcinoma gastric adenocarcinoma gastroesophageal junction cancer DNA methylation circulating tumor DNA cancer biomarker |
| url | http://www.sciencedirect.com/science/article/pii/S2949819824000657 |
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