Liquid Biopsies


The sequencing of circulating DNA [VanderVaart, Ann. NY Acad. Sc. 2008] has emerged as a powerful non-invasive tool in the diagnosis and monitoring of diseases (prominently including cancer [Leary, Science Transl. Med. 2010; Bettegowda, Science Transl. Med. 2014]), and for pre-natal diagnoses [Lo, Science Transl. Med. 2010]. However, robust open-source statistical tools for the interpretation of these data are lacking, and this deficiency is currently a major limitation for the usability of the technology. Here we will develop such tools, with five types of experiment considered:

  • Whole-genome or exome profiling of circulating tumour DNA,
  • Profiling of circulating DNA of a standard gene panel (where many comparable reference data sets are available from multiple patients),
  • Monitoring over time of bespoke mutations identified in a patient,
  • Profiling of circulating mitochondrial tumour DNA [Fliss, Science 2000], and
  • Profiling of other circulating markers [Widschwendter, Clin. Canc. Res. 2006; El-Hefnawy, Clinical Chem. 2004].

To develop and test our methods, we will employ two prototypic data sets: one consists of circulating DNA from ovarian cancer (provided by Dr James Brenton at the Cancer Research UK Cambridge Institute), while the second is from oesophageal adenocarcinoma (provided by Professor Rebecca Fitzgerald at the MRC Cancer Unit at the University of Cambridge).

Participating partners

  • University of Cambridge (Lead Partner)
  • European Molecular Biology Laboratory, Heidelberg
  • Roswell Park Cancer Comprehensive Center, Buffalo
  • ETH Zurich