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 () and Andrea Sottoriva ()
Additional contact information
George D. Cresswell: The Institute of Cancer Research
Daniel Nichol: The Institute of Cancer Research
Inmaculada Spiteri: The Institute of Cancer Research
Haider Tari: The Institute of Cancer Research
Luis Zapata: The Institute of Cancer Research
Timon Heide: The Institute of Cancer Research
Carlo C. Maley: Arizona State University
Luca Magnani: Imperial College London
Gaia Schiavon: Royal Marsden Hospital
Alan Ashworth: UCSF Helen Diller Family Comprehensive Cancer Center
Peter Barry: Royal Marsden Hospital
Andrea Sottoriva: The Institute of Cancer Research

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-15047-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15047-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-15047-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().