Mapping the breast cancer metastatic cascade onto ctDNA using genetic and epigenetic clonal tracking

George D. Cresswell, Daniel Nichol, Inmaculada Spiteri, Haider Tari, Luis Zapata, Timon Heide, Carlo C. Maley, Luca Magnani, Gaia Schiavon, Alan Ashworth, Peter Barry, Andrea Sottoriva

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Circulating tumour DNA (ctDNA) allows tracking of the evolution of human cancers at high resolution, overcoming many limitations of tissue biopsies. However, exploiting ctDNA to determine how a patient’s cancer is evolving in order to aid clinical decisions remains difficult. This is because ctDNA is a mix of fragmented alleles, and the contribution of different cancer deposits to ctDNA is largely unknown. Profiling ctDNA almost invariably requires prior knowledge of what genomic alterations to track. Here, we leverage on a rapid autopsy programme to demonstrate that unbiased genomic characterisation of several metastatic sites and concomitant ctDNA profiling at whole-genome resolution reveals the extent to which ctDNA is representative of widespread disease. We also present a methylation profiling method that allows tracking evolutionary changes in ctDNA at single-molecule resolution without prior knowledge. These results have critical implications for the use of liquid biopsies to monitor cancer evolution in humans and guide treatment.

Original languageEnglish (US)
Article number1446
JournalNature communications
Issue number1
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


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