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Genomic evolution of breast cancer metastasis and relapse

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Date
14/08/2017
Author
Yates, Lucy R.
Knappskog, Stian
Wedge, David
Farmery, James H. R.
Gonzalez, Santiago
Martincorena, Inigo
Alexandrov, Ludmil B.
Van Loo, Peter
Haugland, Hans Kristian
Lilleng, Peer Kaare
Gundem, Gunes
Gerstung, Moritz
Pappaemmanuil, Elli
Gazinska, Patrycja
Bhosle, Shriram G
Jones, David
Raine, Keiran
Mudie, Laura
Latimer, Calli
Sawyer, Elinor
Desmedt, Christine
Sotiriou, Christos
Stratton, Michael R.
Sieuwerts, Anieta M.
Lynch, Andy G.
Martens, John W.
Richardson, Andrea L.
Tutt, Andrew
Lønning, Per Eystein
Campbell, Peter J.
Keywords
Breast cancer
Metastasis
Relapse
Genomics
Somatic mutation
RC0254 Neoplasms. Tumors. Oncology (including Cancer)
QH301 Biology
QH426 Genetics
DAS
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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.
Citation
Yates , L R , Knappskog , S , Wedge , D , Farmery , J H R , Gonzalez , S , Martincorena , I , Alexandrov , L B , Van Loo , P , Haugland , H K , Lilleng , P K , Gundem , G , Gerstung , M , Pappaemmanuil , E , Gazinska , P , Bhosle , S G , Jones , D , Raine , K , Mudie , L , Latimer , C , Sawyer , E , Desmedt , C , Sotiriou , C , Stratton , M R , Sieuwerts , A M , Lynch , A G , Martens , J W , Richardson , A L , Tutt , A , Lønning , P E & Campbell , P J 2017 , ' Genomic evolution of breast cancer metastasis and relapse ' , Cancer Cell , vol. 32 , no. 2 , e7 , pp. 169-184 . https://doi.org/10.1016/j.ccell.2017.07.005
Publication
Cancer Cell
Status
Peer reviewed
DOI
https://doi.org/10.1016/j.ccell.2017.07.005
ISSN
1535-6108
Type
Journal article
Rights
© 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Description
A.G.L. and J.H.R.F. were supported by a Cancer Research UK Program Grant to Simon Tavaré (C14303/A17197).
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  • University of St Andrews Research
URL
http://www.sciencedirect.com/science/article/pii/S1535610817302970?via%3Dihub#app2
URI
http://hdl.handle.net/10023/11553

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