Molecular profiling of single circulating tumour cells with diagnostic intention
Session type: Symposia
Several hundred clinical trials currently explore the role of circulating tumour cell (CTC) analysis for therapy decisions, but assays are lacking for comprehensive molecular characterisation of CTCs with diagnostic precision. We therefore combined a workflow for CTC enrichment and isolation with 100% purity using a non-random whole genome amplification method for single cells. We then developed an assay to predict the outcome of downstream molecular analyses of single CTCs. This assay tested the quality of the whole genome amplification and the genomic integrity of isolated cells and allows identifying CTCs for which more than 90% tested molecular studies were successfully performed, including targeted analysis of point mutations, identification of gene copy number alterations such as ERBB2 amplification or genome wide analyses by aCGH. The selection of high-quality samples enabled to determine the molecular heterogeneity of single CTCs of metastatic breast cancer patients. We readily identified genomic disparity of potentially high relevance between primary tumours and CTCs. Microheterogeneity analysis among individual CTCs uncovered pre-existing cells resistant to ERBB2‐targeted therapies suggesting on-going microevolution at late stage disease whose exploration may provide essential information for personalised treatment decisions and shed light into mechanisms of acquired drug resistance.