Impact of Whole Genome Doubling on Detection of Circulating Tumor DNA in Colorectal Cancer.

Autor: Kabel J; Department of Molecular Medicine, Aarhus University Hospital, 8200 Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark., Henriksen TV; Department of Molecular Medicine, Aarhus University Hospital, 8200 Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark., Demuth C; Department of Molecular Medicine, Aarhus University Hospital, 8200 Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark., Frydendahl A; Department of Molecular Medicine, Aarhus University Hospital, 8200 Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark., Rasmussen MH; Department of Molecular Medicine, Aarhus University Hospital, 8200 Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark., Nors J; Department of Molecular Medicine, Aarhus University Hospital, 8200 Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark., Birkbak NJ; Department of Molecular Medicine, Aarhus University Hospital, 8200 Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark., Madsen AH; Department of Surgery, Regional Hospital Herning, 7400 Herning, Denmark., Løve US; Department of Surgery, Regional Hospital Viborg, 8800 Viborg, Denmark., Andersen PV; Department of Surgery, Odense University Hospital, 5000 Odense, Denmark., Kolbro T; Department of Surgery, Odense University Hospital, 5700 Svendborg, Denmark., Monti A; Department of Surgery, Hjørring Hospital, 9800 Hjørring, Denmark., Thorlacius-Ussing O; Clinical Cancer Research Center, Aalborg University, 9000 Aalborg, Denmark., Gögenur M; Center for Surgical Sciences, Zealand University Hospital, 4600 Køge, Denmark., Kildsig J; Department of Surgery, Copenhagen University Hospital, 2730 Herlev, Denmark., Schlesinger NH; Department of Surgery, University Hospital Bispebjerg, 2400 Copenhagen, Denmark., Bondeven P; Department of Surgery, Regional Hospital Randers, 8900 Randers, Denmark., Iversen LH; Department of Surgery, Aarhus University Hospital, 8200 Aarhus, Denmark., Gotschalck KA; Department of Surgery, Regional Hospital Horsens, 8700 Horsens, Denmark., Andersen CL; Department of Molecular Medicine, Aarhus University Hospital, 8200 Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2023 Feb 10; Vol. 15 (4). Date of Electronic Publication: 2023 Feb 10.
DOI: 10.3390/cancers15041136
Abstrakt: Objective: Circulating tumor DNA (ctDNA) is a candidate biomarker of cancer with practice-changing potential in the detection of both early and residual disease. Disease stage and tumor size affect the probability of ctDNA detection, whereas little is known about the influence of other tumor characteristics on ctDNA detection. This study investigates the impact of tumor cell whole-genome doubling (WGD) on the detection of ctDNA in plasma collected preoperatively from newly diagnosed colorectal cancer (CRC) patients.
Methods: WGD was estimated from copy numbers derived from whole-exome sequencing (WES) data of matched tumor and normal DNA from 833 Danish CRC patients. To explore if tumor WGD status impacts ctDNA detection, we applied tumor-informed ctDNA analysis to preoperative plasma samples from all patients.
Results: Patients with WGD+ tumors had 53% increased odds of being ctDNA positive (OR = 1.53, 95%CI: 1.12-2.09). After stratification for UICC stage, the association persisted for Stage I (OR = 2.44, 95%CI: 1.22-5.03) and Stage II (OR = 1.76, 95%CI: 1.11-2.81) but not for Stage III (OR = 0.83, 95%CI: 0.44-1.53) patients.
Conclusion: The presence of WGD significantly increases the probability of detecting ctDNA, particularly for early-stage disease. In patients with more advanced disease, the benefit of WGD on ctDNA detection is less pronounced, consistent with increased DNA shedding from these tumors, making ctDNA detection less dependent on the amount of ctDNA released per tumor cell.
Databáze: MEDLINE
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