Aaron Beasley, Edith Cowan UniversityFollow
Muhammad K. Khattak, Edith Cowan UniversityFollow
James B. Freeman, Edith Cowan UniversityFollow
Fred K. Chen
Michelle R. Pereira, Edith Cowan UniversityFollow
Leslie Calapre, Edith Cowan UniversityFollow
Melanie R. Ziman, Edith Cowan UniversityFollow
Elin S. Gray, Edith Cowan UniversityFollow
James Freeman Orcid: https://orcid.org/0000-0001-8065-8416 Melanie Ziman Orcid: https://orcid.org/0000-0001-7527-3538 Elin Gray Orcid: https://orcid.org/0000-0002-8613-3570
JCO Precision Oncology
American Society of Clinical Oncology
School of Medical and Health Sciences
NHMRC Number: 1046711
Purpose To evaluate the feasibility of using circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) for the management of uveal melanoma (UM).
Patients and Methods Low-coverage whole-genome sequencing was used to determine somatic chromosomal copy number alterations (SCNAs) in primary UM tumors, ctDNA, and whole-genome amplified CTCs. CTCs were immunocaptured using an antimelanoma-associated chondroitin sulfate antibody conjugated to magnetic beads and immunostained for melanoma antigen recognised by T cells 1 (MART1)/glycoprotein 100 (gp100)/S100 calcium-binding protein β (S100β). ctDNA was quantified using droplet digital polymerase chain reaction assay for mutations in the GNAQ, GNA11, PLCβ4, and CYSLTR2 genes.
Results SCNA analysis of CTCs and ctDNA isolated from a patient with metastatic UM showed good concordance with the enucleated primary tumor. In a cohort of 30 patients with primary UM, CTCs were detected in 58% of patients (one to 37 CTCs per 8 mL of blood), whereas only 26% of patients had detectable ctDNA (1.6 to 29 copies/mL). The presence of CTCs or ctDNA was not associated with tumor size or other prognostic markers. However, the frequent detection of CTCs in patients with early-stage UM supports a model in which CTCs can be used to derive tumor-specific SCNA relevant for prognosis. Monitoring of ctDNA after treatment of the primary tumor allowed detection of metastatic disease earlier than 18F-labeled fluorodeoxyglucose positron emission tomography in two patients.
Conclusion The presence of CTCs in localized UM can be used to ascertain prognostic SCNA, whereas ctDNA can be used to monitor patients for early signs of metastatic disease. This study paves the way for the analysis of CTCs and ctDNA as a liquid biopsy that will assist with treatment decisions in patients with UM.
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