Circulating tumour cells and plasma DNA for non-invasive monitoring of cancers during their treatment

Michael Speicher1

1Medical University of Graz, Graz, Austria

Abstract

Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) offer a unique opportunity for serially monitoring tumor genomes in a non-invasive fashion from the peripheral blood of patients with cancer, a method which is therefore frequently referred to as a “liquid biopsy”. In order to make whole-genome analysis from plasma DNA amenable to clinical routine applications, we perform whole-genome sequencing from plasma at a shallow sequencing depth to establish a genome-wide copy number profile of the tumor at low costs within 2 days. We termed this approach plasma-Seq. In parallel, we sequence a panel of high-interest genes and introns with frequent fusion breakpoints with high coverage. CTCs are subjected to whole-genome amplification (WGA) and the WGA products can be analyzed by similar means. To facilitate the biological and clinical interpretability, we have developed bioinformatics tools for pathway analysis and tumor genome stratification based on liquid biopsy data. Data of our liquid biopsy analyses derived from breast (n=139 plasma samples) and prostate cancer (n=176 plasma samples) will be presented, which includes comparisons of results obtained using CTCs and ctDNA as well as novel insights about the plasticity and dynamics of clonal evolution of tumor genomes.