Abstract

Monitoring the Cancer Genome in Plasma using Circulating DNA

Nitzan Rosenfeld, Senior Group Leader/CSO, University of Cambridge

In patients with solid malignancies, cell-free DNA carrying tumour-specific sequences can be found in body fluids such as blood plasma. This circulating tumour DNA (ctDNA) contains representation of the entire cancer genome, broken down into short mutation-carrying fragments, whose relative levels vary in response to treatment and progression. In cases where a biopsy is hard to obtain, a ‘liquid biopsy’ using circulating tumour DNA can be used to assess cancer mutations. Targeted sequencing of limited regions in circulating DNA can allow identification of de novo mutations. Quantification of ctDNA levels may be useful as a prognostic biomarker and to assess changes in tumour burden in response to treatment or identify progression. When cancer overcomes treatment and progresses, the fraction of mutant alleles in plasma DNA can reach levels of 10%~20% or more, which makes it possible to study cancer evolution noninvasively by whole-genome or exome analysis of plasma DNA. Routine monitoring of tumour-specific and actionable mutations in plasma may provide a framework for rational adaptive cancer therapy, targeting the most aggressive or treatable clones.