Whole‐genome sequencing of cell‐free DNA reveals DNA of tumor origin in plasma from patients with colorectal adenomas
The presence of circulating tumor DNA (ctDNA) in patients with colorectal adenomas remains uncertain. Studies using tumor‐agnostic approaches report ctDNA in 10–15% of patients, though with uncertainty as to whether the signal originates from the adenoma. To obtain an accurate estimate of the propor...
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Wiley
2025-04-01
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| Series: | Molecular Oncology |
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| Online Access: | https://doi.org/10.1002/1878-0261.13803 |
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| author | Amanda Frydendahl Adam J. Widman Nadia Øgaard Anushri Arora Daniel Halmos Jesper Nors Johanne Ahrenfeldt Tenna V. Henriksen Christina Demuth Line Raaby Mads H. Rasmussen Christina Therkildsen Dan A. Landau Claus L. Andersen |
| author_facet | Amanda Frydendahl Adam J. Widman Nadia Øgaard Anushri Arora Daniel Halmos Jesper Nors Johanne Ahrenfeldt Tenna V. Henriksen Christina Demuth Line Raaby Mads H. Rasmussen Christina Therkildsen Dan A. Landau Claus L. Andersen |
| author_sort | Amanda Frydendahl |
| collection | DOAJ |
| description | The presence of circulating tumor DNA (ctDNA) in patients with colorectal adenomas remains uncertain. Studies using tumor‐agnostic approaches report ctDNA in 10–15% of patients, though with uncertainty as to whether the signal originates from the adenoma. To obtain an accurate estimate of the proportion of patients with ctDNA, a sensitive tumor‐informed strategy is preferred, as it ensures the detected signal originates from the adenoma. Here, tumor‐informed whole‐genome sequencing‐based ctDNA analysis (MRD‐EDGESNV) was applied to two independent cohorts. Cohort 1, comprising 93 patients with stage III colorectal cancer (CRC) and 40 healthy individuals, was used to establish the signal threshold at 95% specificity. This threshold was then applied to Cohort 2, consisting of 22 patients with symptomatic and 20 with asymptomatic adenomas. In stage III, MRD‐EDGESNV had an area under the curve of 0.98. ctDNA was detected in 50% and 25% of patients with symptomatic and asymptomatic adenomas, respectively. The median adenoma plasma tumor fraction was 5.9 × 10−5. These finding not only demonstrate the feasibility of ctDNA detection in patients with colorectal adenomas, but also provides an estimate of the necessary sensitivity required to detect these lesions, paving the way for future ctDNA‐based screening strategies. |
| format | Article |
| id | doaj-art-e335d91c65fa4eff89a20d179d1a2940 |
| institution | OA Journals |
| issn | 1574-7891 1878-0261 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj-art-e335d91c65fa4eff89a20d179d1a29402025-08-20T02:08:57ZengWileyMolecular Oncology1574-78911878-02612025-04-0119498499310.1002/1878-0261.13803Whole‐genome sequencing of cell‐free DNA reveals DNA of tumor origin in plasma from patients with colorectal adenomasAmanda Frydendahl0Adam J. Widman1Nadia Øgaard2Anushri Arora3Daniel Halmos4Jesper Nors5Johanne Ahrenfeldt6Tenna V. Henriksen7Christina Demuth8Line Raaby9Mads H. Rasmussen10Christina Therkildsen11Dan A. Landau12Claus L. Andersen13Department of Molecular Medicine Aarhus University Hospital DenmarkMemorial Sloan Kettering Cancer Center New York NY USADepartment of Molecular Medicine Aarhus University Hospital DenmarkNew York Genome Center New York NY USANew York Genome Center New York NY USADepartment of Molecular Medicine Aarhus University Hospital DenmarkDepartment of Molecular Medicine Aarhus University Hospital DenmarkDepartment of Molecular Medicine Aarhus University Hospital DenmarkDepartment of Molecular Medicine Aarhus University Hospital DenmarkDepartment of Molecular Medicine Aarhus University Hospital DenmarkDepartment of Molecular Medicine Aarhus University Hospital DenmarkGastro Unit, Copenhagen University Hospital Amager – Hvidovre Hospital Hvidovre DenmarkNew York Genome Center New York NY USADepartment of Molecular Medicine Aarhus University Hospital DenmarkThe presence of circulating tumor DNA (ctDNA) in patients with colorectal adenomas remains uncertain. Studies using tumor‐agnostic approaches report ctDNA in 10–15% of patients, though with uncertainty as to whether the signal originates from the adenoma. To obtain an accurate estimate of the proportion of patients with ctDNA, a sensitive tumor‐informed strategy is preferred, as it ensures the detected signal originates from the adenoma. Here, tumor‐informed whole‐genome sequencing‐based ctDNA analysis (MRD‐EDGESNV) was applied to two independent cohorts. Cohort 1, comprising 93 patients with stage III colorectal cancer (CRC) and 40 healthy individuals, was used to establish the signal threshold at 95% specificity. This threshold was then applied to Cohort 2, consisting of 22 patients with symptomatic and 20 with asymptomatic adenomas. In stage III, MRD‐EDGESNV had an area under the curve of 0.98. ctDNA was detected in 50% and 25% of patients with symptomatic and asymptomatic adenomas, respectively. The median adenoma plasma tumor fraction was 5.9 × 10−5. These finding not only demonstrate the feasibility of ctDNA detection in patients with colorectal adenomas, but also provides an estimate of the necessary sensitivity required to detect these lesions, paving the way for future ctDNA‐based screening strategies.https://doi.org/10.1002/1878-0261.13803adenomascirculating tumor DNAcolorectal cancerearly detectionwhole‐genome sequencing |
| spellingShingle | Amanda Frydendahl Adam J. Widman Nadia Øgaard Anushri Arora Daniel Halmos Jesper Nors Johanne Ahrenfeldt Tenna V. Henriksen Christina Demuth Line Raaby Mads H. Rasmussen Christina Therkildsen Dan A. Landau Claus L. Andersen Whole‐genome sequencing of cell‐free DNA reveals DNA of tumor origin in plasma from patients with colorectal adenomas Molecular Oncology adenomas circulating tumor DNA colorectal cancer early detection whole‐genome sequencing |
| title | Whole‐genome sequencing of cell‐free DNA reveals DNA of tumor origin in plasma from patients with colorectal adenomas |
| title_full | Whole‐genome sequencing of cell‐free DNA reveals DNA of tumor origin in plasma from patients with colorectal adenomas |
| title_fullStr | Whole‐genome sequencing of cell‐free DNA reveals DNA of tumor origin in plasma from patients with colorectal adenomas |
| title_full_unstemmed | Whole‐genome sequencing of cell‐free DNA reveals DNA of tumor origin in plasma from patients with colorectal adenomas |
| title_short | Whole‐genome sequencing of cell‐free DNA reveals DNA of tumor origin in plasma from patients with colorectal adenomas |
| title_sort | whole genome sequencing of cell free dna reveals dna of tumor origin in plasma from patients with colorectal adenomas |
| topic | adenomas circulating tumor DNA colorectal cancer early detection whole‐genome sequencing |
| url | https://doi.org/10.1002/1878-0261.13803 |
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