Abstract

Single cell RNA-sequencing of Circulating Tumor Cells

David Ting, Assistant Professor Of Medicine, Harvard Medical School

Circulating Tumor Cells (CTCs) are thought to be enriched for the precursors of metastasis.  The detection of CTCs has been shown to be a poor prognostic marker across a variety of malignancies.  However, the absolute number of CTCs found across technologies has revealed that CTC numbers do not necessarily correlate with tumor burden. This suggests that CTCs are heterogeneous and the complete metastatic program is not inherent to all CTCs.  To characterize the heterogeneity of CTCs, we have developed methods to perform large scale single cell RNA-sequencing of CTCs across malignancies.  In a pancreatic cancer mouse model we demonstrate that CTCs are heterogeneous and that not all CTCs are the same.  Together, our work suggests that the ability of CTCs to gain access to the vasculature is an early event in tumorigenesis and that characterizing the transcriptome of CTCs will not only provide novel predictive biomarkers, but also mechanistic insight into the metastatic cascade.