Stratification of UM patients into groups with better or worse prognosis is based on clinicopathological and molecular features and is critical for both patient management and for directing patients towards clinical trials. However, the classification of tumours is constrained by the invasiveness of the biopsy procedure and the limited availability of tissues when enucleation is not performed. Here we evaluated the utility of circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA) for the management of uveal melanoma (UM).
CTCs were immunocaptured to magnetic beads, and immunostained for MART1/gp100/S100β. ctDNA was quantified using droplet digital PCR assay for mutations in the GNAQ, GNA11, PLCβ4 and CYSLTR2 genes. Low coverage whole genome sequencing (WGS) were used to determine somatic chromosomal copy number alterations (SCNA) in primary UM tumour, ctDNA and whole genome amplified CTCs.
In a cohort of 30 primary UM patients, CTCs were detected in 58% of patients (1-37 CTCs per 8 mL of blood), while only 26% of cases had detectable ctDNA (1.6-29 copies/mL). Neither the presence of CTCs or ctDNA were associated with tumour size or other prognostic markers. However, we demonstrate that SCNA analysis of CTCs showed great concordance with the enucleated primary tumour. These results supports a model in which CTCs can be used to derive tumour specific SCNA relevant for prognosis. In addition, monitoring of ctDNA after treatment of the primary tumour, allowed detection of metastatic disease earlier than 18F-labeled fluorodeoxyglucose positron emission tomography in two patients that develop metastatic disease during the course of the study.
The presence of CTCs in localised UM can be exploited to ascertain prognostic SCNA, while 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.