Complete Genomics Deep Whole-Genome Sequencing of Circulating Tumor Cells

Circulating tumor cells (CTCs) are considered to be informative non-invasive biopsy for the early detection, diagnosis or therapy guidance of cancer. CTCs also contain most of the heterogeneity found across multiple metastatic sites. In this study, we combine recently improved CTC isolation methods, resulting in almost pure CTCs, with advanced whole genome sequencing (WGS) based on Long Fragment Read (LFR) technology to demonstrate, for the first time, the research and clinical utility of an accurate, comprehensive, phased, and quantitative genomic analysis of CTCs. In particular, genomes of 34 CTCs, collected at two different time points from a patient whose metastatic breast cancer ultimately became resistant to standard treatments, were analyzed as 3072 barcoded sub-genomic compartments of long DNA. An average read coverage of 23X per cell enabled the high-resolution detection of somatic variants, cancer copy number variations (CNVs) and structural variants, including 133 CNVs shorter than 1Mb and an early chromothripsis-like event.]]>
We collected blood from a 61-year old female patient diagnosed with ER-positive/HER2-negative metastatic breast cancer treated at the University of California San Francisco Helen Diller Family Comprehensive Cancer Center. The patient consented to having her samples analyzed and collection of these samples for genomic analysis was approved by the University of California San Francisco institutional review board (Committee on Human Research).]]>