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

Author

Listed:
  • 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
    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
    AstraZeneca, Oncology R&D)

  • Alan Ashworth

    (UCSF Helen Diller Family Comprehensive Cancer Center)

  • Peter Barry

    (Royal Marsden Hospital)

  • Andrea Sottoriva

    (The Institute of Cancer Research)

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.

Suggested Citation

  • 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, 2020. "Mapping the breast cancer metastatic cascade onto ctDNA using genetic and epigenetic clonal tracking," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15047-9
    DOI: 10.1038/s41467-020-15047-9
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    Cited by:

    1. Humberto Contreras-Trujillo & Jiya Eerdeng & Samir Akre & Du Jiang & Jorge Contreras & Basia Gala & Mary C. Vergel-Rodriguez & Yeachan Lee & Aparna Jorapur & Areen Andreasian & Lisa Harton & Charles S, 2021. "Deciphering intratumoral heterogeneity using integrated clonal tracking and single-cell transcriptome analyses," Nature Communications, Nature, vol. 12(1), pages 1-14, December.

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