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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. Lastly, these include a number of clinically actionable alterations and mutations inactivating SWI-SNF and JAK2-STAT3 pathways.

Authors:
 [1];  [2];  [3];  [4];  [5];  [6];  [7];  [8];  [9];  [9];  [10];  [5];  [10];  [11];  [6];  [6];  [6];  [6];  [6];  [12] more »;  [13];  [13];  [6];  [14];  [4];  [15];  [16];  [17];  [2];  [6] « less
  1. Wellcome Trust Sanger Inst., Hinxton (United Kingdom); English National Health Service (NHS), London (United Kingdom). Guys and St Thomas' NHS Trust, Dept. of Clinical Oncology
  2. Univ. of Bergen (Norway). Section of Oncology, Dept. of Clinical Science; Haukeland University Hospital, Bergen (Norway). Dept. of Clinical Science
  3. Wellcome Trust Sanger Inst., Hinxton (United Kingdom); Univ. of Oxford (United Kingdom). Big Data Inst.
  4. Univ. of Cambridge (United Kingdom). Cancer Research UK Cambridge Inst.
  5. Wellcome Trust Sanger Inst., Hinxton (United Kingdom); European Bioinformatics Inst. EMBL-EBI, Hinxton (United Kingdom)
  6. Wellcome Trust Sanger Inst., Hinxton (United Kingdom)
  7. Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Univ. of New Mexico Comprehensive Cancer Center, Albuquerque, NM (United States)
  8. Francis Crick Inst., London (United Kingdom); Univ. of Leuven (Belgium)
  9. Haukeland Univ. Hospital, Bergen (Norway). Dept. of Pathology; Univ. of Bergen, Bergen (Norway). Gade Lab. for Pathology, Dept. of Clinical Medicine
  10. Wellcome Trust Sanger Inst., Hinxton (United Kingdom); Memorial Sloan Kettering Cancer Inst., New York, NY (United States). Computational Oncology, Epidemiology and Biostatistics
  11. King's College London (United Kingdom). Division of Cancer Studies
  12. English National Health Service (NHS), London (United Kingdom). Guys and St Thomas' NHS Trust, Dept. of Clinical Oncology; King's College London (United Kingdom). Division of Cancer Studies
  13. Univ. Libre de Bruxelles, Brussels (Belgium). Breast Cancer Translational Research Lab.
  14. Erasmus Univ. Medical Center, Rotterdam (Netherlands). Erasmus MC Cancer Inst. and Cancer Genomics Netherlands
  15. Erasmus Univ. Medical Center, Rotterdam (Netherlands). Erasmus MC Cancer Inst. and Cancer Genomics Netherlands
  16. Brigham and Women's Hospital (Harvard Medical School), Boston, MA (United States). Dept. of Pathology; Dana-Farber Cancer Inst., Boston, MA (United States)
  17. King's College Lo Division of Cancer Studies; King's College London (United Kingdom). Breast Cancer Now Research Unit; Inst. of Cancer Research, London (United Kingdom). Breast Cancer Now Toby Robins Research Centre
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE Laboratory Directed Research and Development (LDRD) Program; USDOE National Nuclear Security Administration (NNSA); Wellcome Trust; Bergen Research Foundation; Norwegian Cancer Society; Norwegian Research Council
OSTI Identifier:
1392804
Report Number(s):
LA-UR-16-27672
Journal ID: ISSN 1535-6108
Grant/Contract Number:  
AC52-06NA25396
Resource Type:
Accepted Manuscript
Journal Name:
Cancer Cell
Additional Journal Information:
Journal Volume: 32; Journal Issue: 2; Journal ID: ISSN 1535-6108
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; Biological Science; breast cancer; metastasis; relapse; genomics; somatic mutation

Citation Formats

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, and Campbell, Peter J. Genomic Evolution of Breast Cancer Metastasis and Relapse. United States: N. p., 2017. Web. doi:10.1016/j.ccell.2017.07.005.
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. Genomic Evolution of Breast Cancer Metastasis and Relapse. United States. doi:10.1016/j.ccell.2017.07.005.
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, and Campbell, Peter J. Mon . "Genomic Evolution of Breast Cancer Metastasis and Relapse". United States. doi:10.1016/j.ccell.2017.07.005. https://www.osti.gov/servlets/purl/1392804.
@article{osti_1392804,
title = {Genomic Evolution of Breast Cancer Metastasis and Relapse},
author = {Yates, Lucy R. and Knappskog, Stian and Wedge, David and Farmery, James H. R. and Gonzalez, Santiago and Martincorena, Inigo and Alexandrov, Ludmil B. and Van Loo, Peter and Haugland, Hans Kristian and Lilleng, Peer Kaare and Gundem, Gunes and Gerstung, Moritz and Pappaemmanuil, Elli and Gazinska, Patrycja and Bhosle, Shriram G. and Jones, David and Raine, Keiran and Mudie, Laura and Latimer, Calli and Sawyer, Elinor and Desmedt, Christine and Sotiriou, Christos and Stratton, Michael R. and Sieuwerts, Anieta M. and Lynch, Andy G. and Martens, John W. and Richardson, Andrea L. and Tutt, Andrew and Lønning, Per Eystein and Campbell, Peter J.},
abstractNote = {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. Lastly, these include a number of clinically actionable alterations and mutations inactivating SWI-SNF and JAK2-STAT3 pathways.},
doi = {10.1016/j.ccell.2017.07.005},
journal = {Cancer Cell},
number = 2,
volume = 32,
place = {United States},
year = {2017},
month = {8}
}

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Works referencing / citing this record:

Uncovering the signaling landscape controlling breast cancer cell migration identifies novel metastasis driver genes
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Quantitative evidence for early metastatic seeding in colorectal cancer
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Genomic data analysis workflows for tumors from patient-derived xenografts (PDXs): challenges and guidelines
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Patterns of genomic evolution in advanced melanoma
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Roles of the immune system in cancer: from tumor initiation to metastatic progression
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  • Gonzalez, Hugo; Hagerling, Catharina; Werb, Zena
  • Genes & Development, Vol. 32, Issue 19-20
  • DOI: 10.1101/gad.314617.118

Molecular patterns of cancer colonisation in lymph nodes of breast cancer patients
journal, November 2018


Novel and Alternative Targets Against Breast Cancer Stemness to Combat Chemoresistance
journal, October 2019

  • Sridharan, Sangita; Howard, Cory M.; Tilley, Augustus M. C.
  • Frontiers in Oncology, Vol. 9
  • DOI: 10.3389/fonc.2019.01003

Ampelopsin E Reduces the Invasiveness of the Triple Negative Breast Cancer Cell Line, MDA-MB-231
journal, July 2019

  • Tieng, Francis Yew Fu; Latifah, Saiful Yazan; Md Hashim, Nur Fariesha
  • Molecules, Vol. 24, Issue 14
  • DOI: 10.3390/molecules24142619

Molecular characterisation of aromatase inhibitor-resistant advanced breast cancer: the phenotypic effect of ESR1 mutations
journal, December 2018

  • Lopez-Knowles, Elena; Pearson, Alex; Schuster, Gene
  • British Journal of Cancer, Vol. 120, Issue 2
  • DOI: 10.1038/s41416-018-0345-x

Patterns of genomic evolution in advanced melanoma
journal, July 2018


Uncovering the signaling landscape controlling breast cancer cell migration identifies novel metastasis driver genes
journal, July 2019

  • Koedoot, Esmee; Fokkelman, Michiel; Rogkoti, Vasiliki-Maria
  • Nature Communications, Vol. 10, Issue 1
  • DOI: 10.1038/s41467-019-11020-3

Quantitative evidence for early metastatic seeding in colorectal cancer
journal, June 2019


Roles of the immune system in cancer: from tumor initiation to metastatic progression
journal, October 2018

  • Gonzalez, Hugo; Hagerling, Catharina; Werb, Zena
  • Genes & Development, Vol. 32, Issue 19-20
  • DOI: 10.1101/gad.314617.118

Genomic data analysis workflows for tumors from patient-derived xenografts (PDXs): challenges and guidelines
journal, July 2019


Molecular patterns of cancer colonisation in lymph nodes of breast cancer patients
journal, November 2018


Novel and Alternative Targets Against Breast Cancer Stemness to Combat Chemoresistance
journal, October 2019

  • Sridharan, Sangita; Howard, Cory M.; Tilley, Augustus M. C.
  • Frontiers in Oncology, Vol. 9
  • DOI: 10.3389/fonc.2019.01003

Ampelopsin E Reduces the Invasiveness of the Triple Negative Breast Cancer Cell Line, MDA-MB-231
journal, July 2019

  • Tieng, Francis Yew Fu; Latifah, Saiful Yazan; Md Hashim, Nur Fariesha
  • Molecules, Vol. 24, Issue 14
  • DOI: 10.3390/molecules24142619