@article{d080ab8c834d420c8b177bd1c27fe4db,
title = "Genomic Evolution of Breast Cancer Metastasis and Relapse",
abstract = "Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with metastatic breast cancer having dismal survival. We sequenced whole genomes or a panel of 365 genes on 299 samples from 170 patients with locally relapsed or metastatic breast cancer. Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor. Most distant metastases acquired driver mutations not seen in the primary tumor, drawing from a wider repertoire of cancer genes than early drivers. These include a number of clinically actionable alterations and mutations inactivating SWI-SNF and JAK2-STAT3 pathways.",
keywords = "breast cancer, genomics, metastasis, relapse, somatic mutation",
author = "Yates, {Lucy R.} and Stian Knappskog and David Wedge and Farmery, {James H.R.} and Santiago Gonzalez and Inigo Martincorena and Alexandrov, {Ludmil B.} and {Van Loo}, Peter and Haugland, {Hans Kristian} and Lilleng, {Peer Kaare} and Gunes Gundem and Moritz Gerstung and Elli Pappaemmanuil and Patrycja Gazinska and Bhosle, {Shriram G.} and David Jones and Keiran Raine and Laura Mudie and Calli Latimer and Elinor Sawyer and Christine Desmedt and Christos Sotiriou and Stratton, {Michael R.} and Sieuwerts, {Anieta M.} and Lynch, {Andy G.} and Martens, {John W.} and Richardson, {Andrea L.} and Andrew Tutt and L{\o}nning, {Per Eystein} and Campbell, {Peter J.}",
note = "Funding Information: This work was supported by the Wellcome Trust. Work within the project was also supported by the Bergen Research Foundation, the Norwegian Cancer Society, the Norwegian Research Council, Belgian Cancer Plan-Ministry of Health, the Breast Cancer Research Foundation and the Brussels Region, The University of Cambridge, Cancer Research UK, and Hutchison Whampoa Limited. L.R.Y. is funded by a Wellcome Trust research fellowship. P.J.C. is a Wellcome Trust Senior Clinical Fellow. Dr. Papaemmanuil is a Josie Robertson Investigator and the recipient of a European Hematology Association early career fellowship. A.M.S was supported by Cancer Genomics Netherlands (CGC.nl) through a grant from the Netherlands Organisation for Scientific Research (NWO). A.G.L. and J.H.R.F. were supported by a Cancer Research UK Program Grant to Simon Tavar{\'e} (C14303/A17197) We thank Beryl Leirvaag and Dagfinn Ekse of Haukeland University Hospital, Bergen, Norway, for technical assistance. We also acknowledge and thank all members of the laboratory and IT teams within the Cancer Genome Project at the Wellcome Trust Sanger Institute. The laboratory work performed in Bergen was conducted in the Mohn Cancer Research Laboratory. This research used resources provided by the Los Alamos National Laboratory Institutional Computing Program, which is supported by the U.S. Department of Energy National Nuclear Security Administration under contract no. DE-AC52-06NA25396. Research performed at Los Alamos National Laboratory was carried out under the auspices of the National Nuclear Security Administration of the United States Department of Energy. This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001202), the UK Medical Research Council (FC001202), and the Wellcome Trust (FC001202). The results published here use data generated by the TCGA Research Network: http://cancergenome.nih.gov/. Publisher Copyright: {\textcopyright} 2017 The Authors",
year = "2017",
month = aug,
day = "14",
doi = "10.1016/j.ccell.2017.07.005",
language = "English (US)",
volume = "32",
pages = "169--184.e7",
journal = "Cancer cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "2",
}