Single Cell Analyses of Prostate Cancer Liquid Biopsies Acquired by Apheresis

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 7.5mls 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. Conclusion/Discussion: 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.

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