Single-Cell Analyses of Prostate Cancer Liquid Biopsies Acquired by Apheresis

Maryou B. Lambros, George Seed, Semini Sumanasuriya, Veronica Gil, Mateus Crespo, Mariane Fontes, Rob Chandler, Niven Mehra, Gemma Fowler, Berni Ebbs, Penny Flohr, Susana Miranda, Wei Yuan, Alan Mackay, Ana Ferreira, Rita Pereira, Claudia Bertan, Ines Figueiredo, Ruth Riisnaes, Daniel Nava RodriguesAdam Sharp, Jane Goodall, Gunther Boysen, Suzanne Carreira, Diletta Bianchini, Pasquale Rescigno, Zafeiris Zafeiriou, Joanne Hunt, Deirdre Moloney, Lucy Hamilton, Rui P. Neves, Joost Swennenhuis, Kiki Andree, Nikolas H. Stoecklein, Leon W.M.M. Terstappen, Johann S. De Bono

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Abstract

Purpose: Circulating tumor cells (CTCs) have clinical relevance, but their study has been limited by their low frequency.

Experimental Design: We evaluated liquid biopsies by apheresis to increase CTC yield from patients suffering from metastatic prostate cancer, allow precise gene copy-number calls, and study disease heterogeneity.

Results: Apheresis was well tolerated and allowed the separation of large numbers of CTCs; the average CTC yield from 7.5 mL of peripheral blood was 167 CTCs, whereas the average CTC yield per apheresis (mean volume: 59.5 mL) was 12,546 CTCs. Purified single CTCs could be isolated from apheresis product by FACS sorting; copy-number aberration (CNA) profiles of 185 single CTCs from 14 patients revealed the genomic landscape of lethal prostate cancer and identified complex intrapatient, intercell, genomic heterogeneity missed on bulk biopsy analyses.

Conclusions: Apheresis facilitated the capture of large numbers of CTCs noninvasively with minimal morbidity and allowed the deconvolution of intrapatient heterogeneity and clonal evolution.
Original languageEnglish
Pages (from-to)5635-5644
Number of pages10
JournalClinical cancer research
Volume24
Issue number22
Early online date11 Sep 2018
DOIs
Publication statusPublished - 15 Nov 2018

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    Lambros, M. B., Seed, G., Sumanasuriya, S., Gil, V., Crespo, M., Fontes, M., ... De Bono, J. S. (2018). Single-Cell Analyses of Prostate Cancer Liquid Biopsies Acquired by Apheresis. Clinical cancer research, 24(22), 5635-5644. https://doi.org/10.1158/1078-0432.CCR-18-0862