Single Cell Analyses of Prostate Cancer Liquid Biopsies Acquired by Apheresis

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

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.

Apheresis was well-tolerated and allowed the separation of large numbers of CTCs; the average CTC yield from 7.5mls of peripheral blood was 167 CTCs, whereas the average CTC yield per apheresis (mean volume: 59.5mls) was 12546 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 intra-patient, inter-cell, genomic heterogeneity missed on bulk biopsy analyses.

Apheresis facilitated the capture of large numbers of CTCs non-invasively with minimal morbidity and allowed the deconvolution of intra-patient heterogeneity and clonal evolution.

Clinical cancer research : an official journal of the American Association for Cancer Research. 2018 Aug 09 [Epub ahead of print]

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

The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research., Cancer Biomarkers Team, The Institute of Cancer Research., Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research., Clinical Studies, The Institute of Cancer Research., Section of Medicine, The Institute of Cancer Research., Prostate Cancer Targeted Therapy Group, Royal Marsden NHS Foundation Trust., Royal Marsden NHS Foundation Trust., Clinical Studies Department,, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust., Division of Clinical Studies, The Institute of Cancer Research., Cancer Biomarkers, The Institute of Cancer Research., Clinical Studies, Institute of Cancer Reseach., The Institute of Cancer Research., Prostate Cancer Targeted Therapy Group, The Institute of Cancer Research., The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust., Department of General, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine University Düsseldorf., TNW/MCBP, University of Twente., Medical Cell BioPhysics, University of Twente., Dept. of Surgery (A), University of Duesseldorf, Germany., The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust .