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

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
Article number	e7
Pages (from-to)	169-184
Journal	Cancer Cell
Volume	32
Issue number	2
DOIs	https://doi.org/10.1016/j.ccell.2017.07.005
Publication status	Published - 14 Aug 2017

Keywords

Breast cancer
Metastasis
Relapse
Genomics
Somatic mutation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ccell.2017.07.005Licence: CC BY

Lynch_2017_CancerCell_GenomicEvolution_CC
© 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/).
Final published version, 4.76 MBLicence: CC BY

Cite this

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. Article e7. https://doi.org/10.1016/j.ccell.2017.07.005

@article{63f91eddc9f043b795cff90bded7d6f9,

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, Metastasis, Relapse, Genomics, 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 = "A.G.L. and J.H.R.F. were supported by a Cancer Research UK Program Grant to Simon Tavar{\'e} (C14303/A17197).",

year = "2017",

month = aug,

day = "14",

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

language = "English",

volume = "32",

pages = "169--184",

journal = "Cancer Cell",

issn = "1535-6108",

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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, e7, pp. 169-184. https://doi.org/10.1016/j.ccell.2017.07.005

TY - JOUR

T1 - Genomic evolution of breast cancer metastasis and relapse

AU - Yates, Lucy R.

AU - Knappskog, Stian

AU - Wedge, David

AU - Farmery, James H. R.

AU - Gonzalez, Santiago

AU - Martincorena, Inigo

AU - Alexandrov, Ludmil B.

AU - Van Loo, Peter

AU - Haugland, Hans Kristian

AU - Lilleng, Peer Kaare

AU - Gundem, Gunes

AU - Gerstung, Moritz

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.

N1 - A.G.L. and J.H.R.F. were supported by a Cancer Research UK Program Grant to Simon Tavaré (C14303/A17197).

PY - 2017/8/14

Y1 - 2017/8/14

N2 - 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.

AB - 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.

KW - Breast cancer

KW - Metastasis

KW - Relapse

KW - Genomics

KW - Somatic mutation

UR - http://www.sciencedirect.com/science/article/pii/S1535610817302970?via%3Dihub#app2

U2 - 10.1016/j.ccell.2017.07.005

DO - 10.1016/j.ccell.2017.07.005

M3 - Article

C2 - 28810143

SN - 1535-6108

VL - 32

SP - 169

EP - 184

JO - Cancer Cell

JF - Cancer Cell

IS - 2

M1 - e7

ER -

Genomic evolution of breast cancer metastasis and relapse

Abstract

Keywords

UN SDGs

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Andy Lynch