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The somatic mutation profiles of 2,433 breast cancers refine their genomic and transcriptomic landscapes

Author

Listed:
  • Bernard Pereira

    (Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way
    University of Cambridge)

  • Suet-Feung Chin

    (Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way
    University of Cambridge)

  • Oscar M. Rueda

    (Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way
    University of Cambridge)

  • Hans-Kristian Moen Vollan

    (Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Montebello, Oslo 0310, Norway
    The K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo)

  • Elena Provenzano

    (Cambridge Breast Unit, Addenbrooke’s Hospital, Cambridge University Hospital NHS Foundation Trust and NIHR Cambridge Biomedical Research Centre
    Cambridge Experimental Cancer Medicine Centre, Cambridge University Hospitals NHS)

  • Helen A. Bardwell

    (Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way)

  • Michelle Pugh

    (Inivata, Li Ka Shing Centre, Robinson Way)

  • Linda Jones

    (Cambridge Breast Unit, Addenbrooke’s Hospital, Cambridge University Hospital NHS Foundation Trust and NIHR Cambridge Biomedical Research Centre
    Cambridge Experimental Cancer Medicine Centre, Cambridge University Hospitals NHS)

  • Roslin Russell

    (Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way)

  • Stephen-John Sammut

    (Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way
    University of Cambridge)

  • Dana W. Y. Tsui

    (Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way
    Present address: Center for Molecular Oncology, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA)

  • Bin Liu

    (University of Cambridge)

  • Sarah-Jane Dawson

    (Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way
    Peter MacCallum Cancer Centre)

  • Jean Abraham

    (Cambridge Breast Unit, Addenbrooke’s Hospital, Cambridge University Hospital NHS Foundation Trust and NIHR Cambridge Biomedical Research Centre
    Cambridge Experimental Cancer Medicine Centre, Cambridge University Hospitals NHS)

  • Helen Northen

    (Illumina, Chesterford Research Park, Little Chesterford)

  • John F. Peden

    (Illumina, Chesterford Research Park, Little Chesterford)

  • Abhik Mukherjee

    (School of Medicine, University of Nottingham and Nottingham University Hospital NHS Trust)

  • Gulisa Turashvili

    (Queen’s University/Kingston General Hospital)

  • Andrew R. Green

    (School of Medicine, University of Nottingham and Nottingham University Hospital NHS Trust)

  • Steve McKinney

    (British Columbia Cancer Research Centre)

  • Arusha Oloumi

    (British Columbia Cancer Research Centre)

  • Sohrab Shah

    (British Columbia Cancer Research Centre)

  • Nitzan Rosenfeld

    (Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way)

  • Leigh Murphy

    (Research Institute in Oncology and Hematology)

  • David R. Bentley

    (Illumina, Chesterford Research Park, Little Chesterford)

  • Ian O. Ellis

    (School of Medicine, University of Nottingham and Nottingham University Hospital NHS Trust)

  • Arnie Purushotham

    (NIHR Comprehensive Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and Research Oncology, King’s College London)

  • Sarah E. Pinder

    (NIHR Comprehensive Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and Research Oncology, King’s College London)

  • Anne-Lise Børresen-Dale

    (Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Montebello, Oslo 0310, Norway
    The K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo)

  • Helena M. Earl

    (Cambridge Breast Unit, Addenbrooke’s Hospital, Cambridge University Hospital NHS Foundation Trust and NIHR Cambridge Biomedical Research Centre
    Cambridge Experimental Cancer Medicine Centre, Cambridge University Hospitals NHS)

  • Paul D. Pharoah

    (Strangeways Research Laboratory, University of Cambridge)

  • Mark T. Ross

    (Illumina, Chesterford Research Park, Little Chesterford)

  • Samuel Aparicio

    (British Columbia Cancer Research Centre)

  • Carlos Caldas

    (Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way
    University of Cambridge
    Cambridge Breast Unit, Addenbrooke’s Hospital, Cambridge University Hospital NHS Foundation Trust and NIHR Cambridge Biomedical Research Centre
    Cambridge Experimental Cancer Medicine Centre, Cambridge University Hospitals NHS)

Abstract

The genomic landscape of breast cancer is complex, and inter- and intra-tumour heterogeneity are important challenges in treating the disease. In this study, we sequence 173 genes in 2,433 primary breast tumours that have copy number aberration (CNA), gene expression and long-term clinical follow-up data. We identify 40 mutation-driver (Mut-driver) genes, and determine associations between mutations, driver CNA profiles, clinical-pathological parameters and survival. We assess the clonal states of Mut-driver mutations, and estimate levels of intra-tumour heterogeneity using mutant-allele fractions. Associations between PIK3CA mutations and reduced survival are identified in three subgroups of ER-positive cancer (defined by amplification of 17q23, 11q13–14 or 8q24). High levels of intra-tumour heterogeneity are in general associated with a worse outcome, but highly aggressive tumours with 11q13–14 amplification have low levels of intra-tumour heterogeneity. These results emphasize the importance of genome-based stratification of breast cancer, and have important implications for designing therapeutic strategies.

Suggested Citation

  • Bernard Pereira & Suet-Feung Chin & Oscar M. Rueda & Hans-Kristian Moen Vollan & Elena Provenzano & Helen A. Bardwell & Michelle Pugh & Linda Jones & Roslin Russell & Stephen-John Sammut & Dana W. Y. , 2016. "The somatic mutation profiles of 2,433 breast cancers refine their genomic and transcriptomic landscapes," Nature Communications, Nature, vol. 7(1), pages 1-16, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11479
    DOI: 10.1038/ncomms11479
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    Cited by:

    1. Peter Eirew & Ciara O’Flanagan & Jerome Ting & Sohrab Salehi & Jazmine Brimhall & Beixi Wang & Justina Biele & Teresa Algara & So Ra Lee & Corey Hoang & Damian Yap & Steven McKinney & Cherie Bates & E, 2022. "Accurate determination of CRISPR-mediated gene fitness in transplantable tumours," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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