Genomic Evolution of Breast Cancer Metastasis and Relapse

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

doi:10.1016/j.ccell.2017.07.005

Genomic Evolution of Breast Cancer Metastasis and Relapse

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 SawyerChristine 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

Research output: Contribution to journal › Article › peer-review

241 Scopus citations

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.

Original language	English (US)
Pages (from-to)	169-184.e7
Journal	Cancer cell
Volume	32
Issue number	2
DOIs	https://doi.org/10.1016/j.ccell.2017.07.005
State	Published - Aug 14 2017
Externally published	Yes

Keywords

breast cancer
genomics
metastasis
relapse
somatic mutation

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.ccell.2017.07.005

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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., ... Campbell, P. J. (2017). Genomic Evolution of Breast Cancer Metastasis and Relapse. Cancer cell, 32(2), 169-184.e7. https://doi.org/10.1016/j.ccell.2017.07.005

Yates, LR, Knappskog, S, Wedge, D, Farmery, JHR, Gonzalez, S, Martincorena, I, Alexandrov, LB, Van Loo, P, Haugland, HK, Lilleng, PK, Gundem, G, Gerstung, M, Pappaemmanuil, E, Gazinska, P, Bhosle, SG, Jones, D, Raine, K, Mudie, L, Latimer, C, Sawyer, E, Desmedt, C, Sotiriou, C, Stratton, MR, Sieuwerts, AM, Lynch, AG, Martens, JW, Richardson, AL, Tutt, A, Lønning, PE & Campbell, PJ 2017, 'Genomic Evolution of Breast Cancer Metastasis and Relapse', Cancer cell, vol. 32, no. 2, pp. 169-184.e7. https://doi.org/10.1016/j.ccell.2017.07.005

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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.",

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doi = "10.1016/j.ccell.2017.07.005",

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AU - Martincorena, Inigo

AU - Alexandrov, Ludmil B.

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AU - Pappaemmanuil, Elli

AU - Gazinska, Patrycja

AU - Bhosle, Shriram G.

AU - Jones, David

AU - Raine, Keiran

AU - Mudie, Laura

AU - Latimer, Calli

AU - Sawyer, Elinor

AU - Desmedt, Christine

AU - Sotiriou, Christos

AU - Stratton, Michael R.

AU - Sieuwerts, Anieta M.

AU - Lynch, Andy G.

AU - Martens, John W.

AU - Richardson, Andrea L.

AU - Tutt, Andrew

AU - Lønning, Per Eystein

AU - Campbell, Peter J.

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Genomic Evolution of Breast Cancer Metastasis and Relapse

Abstract

Keywords

ASJC Scopus subject areas

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