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

Carlos Alberto Aya-Bonilla, Michael Morici, Xin Hong, Ashleigh Cavell McEvoy, Ryan Joseph Sullivan, James Freeman, Leslie Calapre, Muhammad Adnan Khattak, Tarek Meniawy, Michael Millward, Mel Ziman, Elin Solomonovna Gray

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1059-1067
Number of pages9
JournalBritish Journal of Cancer
Volume122
Issue number7
DOIs
Publication statusPublished - 31 Mar 2020

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    Aya-Bonilla, C. A., Morici, M., Hong, X., McEvoy, A. C., Sullivan, R. J., Freeman, J., Calapre, L., Khattak, M. A., Meniawy, T., Millward, M., Ziman, M., & Gray, E. S. (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