Detection and prognostic role of heterogeneous populations of melanoma circulating tumour cells

Abstract

Background: Circulating tumour cells (CTCs) can be assessed through a minimally invasive blood sample with potential utility as a predictive, prognostic and pharmacodynamic biomarker. The large heterogeneity of melanoma CTCs has hindered their detection and clinical application. Methods: Here we compared two microfluidic devices for the recovery of circulating melanoma cells. The presence of CTCs in 43 blood samples from patients with metastatic melanoma was evaluated using a combination of immunocytochemistry and transcript analyses of five genes by RT-PCR and 19 genes by droplet digital PCR (ddPCR), whereby a CTC score was calculated. Circulating tumour DNA (ctDNA) from the same patient blood sample, was assessed by ddPCR targeting tumour-specific mutations. Results: Our analysis revealed an extraordinary heterogeneity amongst melanoma CTCs, with multiple non-overlapping subpopulations. CTC detection using our multimarker approach was associated with shorter overall and progression-free survival. Finally, we found that CTC scores correlated with plasma ctDNA concentrations and had similar pharmacodynamic changes upon treatment initiation. Conclusions: Despite the high phenotypic and molecular heterogeneity of melanoma CTCs, multimarker derived CTC scores could serve as viable tools for prognostication and treatment response monitoring in patients with metastatic melanoma. © 2020, The Author(s), under exclusive licence to Cancer Research UK.

RAS ID

31432

Document Type

Journal Article

Date of Publication

1-1-2020

Funding Information

Edith Cowan University, ECU

National Health and Medical Research Council, NHMRC

School

School of Medical and Health Sciences

Grant Number

NHMRC Number : 1013349

Copyright

subscription content

Publisher

Springer Nature

Comments

Aya-Bonilla, C. A., Morici, M., Hong, X., McEvoy, A. C., Sullivan, R. J., Freeman, J., ... & Ziman, M. (2020). Detection and prognostic role of heterogeneous populations of melanoma circulating tumour cells. British Journal of Cancer, 122(7), 1059-1067. https://doi.org/10.1038/s41416-020-0750-9

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Link to publisher version (DOI)

10.1038/s41416-020-0750-9