@article{bdc7f45899674a30bb2af3631b3bbc85,
title = "Mapping the breast cancer metastatic cascade onto ctDNA using genetic and epigenetic clonal tracking",
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{\textquoteright}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.",
author = "Cresswell, {George D.} and Daniel Nichol and Inmaculada Spiteri and Haider Tari and Luis Zapata and Timon Heide and Maley, {Carlo C.} and Luca Magnani and Gaia Schiavon and Alan Ashworth and Peter Barry and Andrea Sottoriva",
note = "Funding Information: The authors acknowledge funding from Breast Cancer Now and the Royal Marsden and ICR NIHR Biomedical Research Centre. A.S. is supported by Wellcome Trust (202778/B/ 16/Z) and Cancer Research UK (A22909). We also acknowledge funding from the National Institute of Health (NCI U54 CA217376) to A.S. and C.C.M. This work was also supported by a Wellcome Trust award to the Centre for Evolution and Cancer (105104/ Z/14/Z). H.T. is supported by Cancer Research UK (A23536). L.Z. is supported by the European Union{\textquoteright}s Horizon 2020 research and innovation programme under the Marie Sk{\l}odowska-Curie Research Fellowship scheme (846614). C.C.M. was supported in part by NIH grants U54 CA217376, P01 CA91955, R01 CA170595, R01 CA185138 and R01 CA140657 as well as CDMRP Breast Cancer Research Program Award BC132057 and an Arizona Investigator Grant ADHS18-198847. We also acknowledge funding of the Pilot LEGACY programme by Breast Cancer Now (Breakthrough Breast Cancer) UK. L.M. is supported by Cancer Research UK (A23110). Image from Figs. 1a and 3a was taken from Servier Medical Art (licensed under a Creative Commons Attribution 3.0 Unported License). A UK patent application has been submitted in relation to the use of methylation clocks (application number 2000747.2). Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41467-020-15047-9",
language = "English (US)",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}
