Abstract

Longitudinal Whole Exome Investigation of Mutational Heterogeneity in Single CTCs in a Patient with Triple-Negative Breast Cancer

Eric Kaldjian, Chief Medical Officer, RareCyte

We performed whole exome sequencing of single CTCs from a patient with metastatic triple-negative breast cancer to investigate the evolution of genetic heterogeneity during therapy.  CTCs were identified using the AccuCyte-CyteFinder system (RareCyte) and individually retrieved from microscope slides using the integrated CytePicker function.  Single cell whole genome amplication was performed followed by whole exome sequencing.   Computational biology tools were employed to analyze genomic DNA sequence from multiple CTCs, white blood cells and ctDNA from various time points. Genomic sequence alterations were observed to evolve over the course of therapy in individual CTCs.  These alterations appear to be generally consistent within CTC at a given time point.  The number of predicted deleterious and cancer driver mutations per CTC were observed to increase in frequency after effective treatments, suggesting that the number of such alterations may be associated with resistance to therapy.