Comprehensive characterization of circulating tumor cells and cell-free DNA in patients with metastatic melanoma.

Autor: Bos MK; Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands., Kraan J; Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands., Starmans MPA; Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands., Helmijr JCA; Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands., Verschoor N; Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands., De Jonge MJA; Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands., Joosse A; Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands., van der Veldt AAM; Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands.; Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands., Te Boekhorst PAW; Department of Hematology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands., Martens JWM; Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands., Sleijfer S; Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands., Wilting SM; Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Molecular oncology [Mol Oncol] 2024 Nov; Vol. 18 (11), pp. 2770-2782. Date of Electronic Publication: 2024 May 24.
DOI: 10.1002/1878-0261.13650
Abstrakt: Advances in therapeutic approaches for melanoma urge the need for biomarkers that can identify patients at risk for recurrence and to guide treatment. The potential use of liquid biopsies in identifying biomarkers is increasingly being recognized. Here, we present a head-to-head comparison of several techniques to analyze circulating tumor cells (CTCs) and cell-free DNA (cfDNA) in 20 patients with metastatic melanoma. In this study, we investigated whether diagnostic leukapheresis (DLA) combined with multimarker flow cytometry (FCM) increased the detection of CTCs in blood compared to the CellSearch platform. Additionally, we characterized cfDNA at the level of somatic mutations, extent of aneuploidy and genome-wide DNA methylation. Both CTCs and cfDNA measures were compared to tumor markers and extracranial tumor burden on radiological imaging. Compared to the CellSearch method applied on peripheral blood, DLA combined with FCM increased the proportion of patients with detectable CTCs from 35% to 70% (P = 0.06). However, the median percentage of cells that could be recovered by the DLA procedure was 29%. Alternatively, cfDNA mutation and methylation analysis detected tumor load in the majority of patients (90% and 93% of samples successfully analyzed, respectively). The aneuploidy score was positive in 35% of all patients. From all tumor measurements in blood, lactate dehydrogenase (LDH) levels were significantly correlated to variant allele frequency (P = 0.004). Furthermore, the presence of CTCs in DLA was associated with tumor burden (P < 0.001), whereas the presence of CTCs in peripheral blood was associated with number of lesions on radiological imaging (P < 0.001). In conclusion, DLA tended to increase the proportion of patients with detectable CTCs but was also associated with low recovery. Both cfDNA and CTCs were correlated with clinical parameters such as LDH levels and extracranial tumor burden.
(© 2024 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Databáze: MEDLINE
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