Mapping the breast cancer metastatic cascade onto ctDNA using genetic and epigenetic clonal tracking.
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Date
2020-03-27ICR Author
Author
Cresswell, GD
Nichol, D
Spiteri, I
Tari, H
Zapata, L
Heide, T
Maley, CC
Magnani, L
Schiavon, G
Ashworth, A
Barry, P
Sottoriva, A
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Clone Cells
Humans
Breast Neoplasms
Neoplasm Metastasis
DNA Methylation
Epigenesis, Genetic
Drug Resistance, Neoplasm
Genome, Human
Female
Clonal Evolution
Circulating Tumor DNA
Research team
Evolutionary Genomics & Modelling
Language
eng
Date accepted
2020-02-18
License start date
2020-03-27
Citation
Nature communications, 2020, 11 (1), pp. 1446 - ?
Publisher
NATURE PORTFOLIO