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Title: Genomic Evolution of Breast Cancer Metastasis and Relapse

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:
Report Number(s):
LA-UR-16-27672
Journal ID: ISSN 1535-6108
Grant/Contract Number:
AC52-06NA25396
Type:
Accepted Manuscript
Journal Name:
Cancer Cell
Additional Journal Information:
Journal Volume: 32; Journal Issue: 2; Journal ID: ISSN 1535-6108
Publisher:
Elsevier
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
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
OSTI Identifier:
1392804