November 16, 2016
Epic Sciences, in collaboration with pharma co-authors, published an analytic validation of their sequencing assay in single circulating tumor cells (CTC) and demonstrated clinical feasibility in metastatic prostate cancer patients (mCRPC). In addition to profiling genome wide copy number variation (CNV) from single cells, the authors also validated the ability to characterize the extent of genomic instability within individual CTCs. The study "Chromosomal Instability Estimation Based on Next Generation Sequencing and Single Cell Genome Wide Copy Number Variation Analysis" published today in PLOS ONE utilizing the Epic Sciences "No Cell Left Behind" CTC platform.
After CTC identification, individual CTCs were isolated, lysed, whole genome amplified, and low pass whole genome sequenced for the presence of both focal copy number alterations indicative of genomic instability. Blood samples from mCRPC patients were analyzed for CTC prevalence. CTC subtypes were identified, and individual cells were isolated, sequenced and analyzed.
"Importantly, we demonstrated that single cell sequencing from blood samples on our platform reproducibly and accurately recapitulated data from genomic DNA bulk controls," said Mark Landers, vice president of translational research and corresponding author on the study. "In the study, single CTC sequencing identified novel sub-clonal drivers of disease progression, and provided insight into the heterogeneity and clonality of the active metastatic tumor burden from a real time liquid biopsy."
Further analysis into CTC genomic instability identified sub-clonal populations of CTCs with high levels of genomic instability within individual mCRPC patients, providing evidence for somatic or acquired genomic alterations. "The presence of sub-clonal CTCs with high genomic instability, identifies a significant clinical opportunity to use CTC analysis to find patients who may benefit from novel HRD targeting therapeutics, such as PARP inhibitors or platinum based chemotherapies," said Landers.
To date, Epic Sciences has sequenced over 7,000 single CTC genomes from multiple cancer types. "The genomic information gained from this and other studies has provided us with a unique view of tumor evolution and the emergence of therapeutic resistance, which can't be seen through tissue or cell free DNA analysis," said Landers. "In particular, the ability to identify which genomic alterations are present within specific CTC subpopulations and the response of those subpopulations to both standard of care and investigational therapeutics, is a powerful tool to functionally understand the impact of cancer heterogeneity and guide drug development. We have had strong uptake of our single CTC sequencing solutions from our biopharma and academic partners and are rapidly scaling our platform to meet current demand."
The research paper is available here: http://dx.plos.org/10.1371/journal.pone.0165089