TY - JOUR
T1 - Impact of Whole Genome Doubling on Detection of Circulating Tumor DNA in Colorectal Cancer
AU - Kabel, Jonas
AU - Henriksen, Tenna Vesterman
AU - Demuth, Christina
AU - Frydendahl, Amanda
AU - Rasmussen, Mads Heilskov
AU - Nors, Jesper
AU - Birkbak, Nicolai J.
AU - Madsen, Anders Husted
AU - Løve, Uffe S.
AU - Andersen, Per Vadgaard
AU - Kolbro, Thomas
AU - Monti, Alessio
AU - Thorlacius-Ussing, Ole
AU - Gögenur, Mikail
AU - Kildsig, Jeppe
AU - Schlesinger, Nis Hallundbæk
AU - Bondeven, Peter
AU - Iversen, Lene Hjerrild
AU - Gotschalck, Kåre Andersson
AU - Andersen, Claus Lindbjerg
PY - 2023/2/10
Y1 - 2023/2/10
N2 - 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.
AB - 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.
KW - cancer diagnostics
KW - circulating tumor DNA
KW - colorectal cancer
KW - whole genome doubling
UR - http://www.scopus.com/inward/record.url?scp=85149124416&partnerID=8YFLogxK
U2 - 10.3390/cancers15041136
DO - 10.3390/cancers15041136
M3 - Journal article
C2 - 36831479
SN - 2072-6694
VL - 15
JO - Cancers
JF - Cancers
IS - 4
M1 - 1136
ER -