Year: 2017
Type: article
Study design: Observational Study
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.
Source: Cancer Cell
Authors: Lucy R. Yates, Stian Knappskog, David Wedge, James H.R. Farmery, Santiago Gonzalez, Inigo Martincorena, Ludmil B. Alexandrov, Peter Van Loo, Hans Kristian Haugland, Peer Kaare Lilleng, Gunes Gundem, Moritz Gerstung, Elli Pappaemmanuil, Patrycja Gazinska, Shriram G. Bhosle, David Jones, Keiran Raine, Laura Mudie, Calli Latimer, Elinor Sawyer, Christine Desmedt, Christos Sotiriou, Michael R. Stratton, Anieta M. Sieuwerts, Andy G. Lynch, John W. Martens, Andrea L. Richardson, Andrew Tutt, Per Eystein Lønning, Peter J. Campbell
Institutions: Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, Wellcome Sanger Institute, Haukeland University Hospital, University of Bergen, University of Oxford, University of Cambridge, Cancer Research UK, European Bioinformatics Institute, Los Alamos National Laboratory, UNM Comprehensive Cancer Center, The Francis Crick Institute, KU Leuven, Memorial Sloan Kettering Cancer Center, King's College London, Université Libre de Bruxelles, Institut Jules Bordet, Erasmus MC, Erasmus MC Cancer Institute, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Dana-Farber Brigham Cancer Center, Institute of Cancer Research, Breast Cancer Now
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Funders: U.S. Department of Energy, Breast Cancer Research Foundation, European Hematology Association, Kreftforeningen, Wellcome Trust, Francis Crick Institute, Cancer Research UK, University of Cambridge, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Norges Forskningsråd, Bergens Forskningsstiftelse, Haukeland Universitetssjukehus, Hutchison Whampoa Limited, National Nuclear Security Administration, Medical Research Council, Los Alamos National Laboratory
Awards: Somatic mutation, clonal dynamics and tumour evolution in premalignant lung disease., G1524023739, G154923120, G1879383613, G189782301, G2864965629, G286898171, G310521049, G3700687868, G434464243, G4653762689, G5638595947, G5657628048, G6137580159, G640145969, G6838766548, G6869983133, G75892134, G7884127298
OpenAlex ID: W2746672093