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The prognostic effects of somatic mutations in ER-positive breast cancer

Author

Listed:
  • Obi L. Griffith

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine)

  • Nicholas C. Spies

    (Washington University School of Medicine)

  • Meenakshi Anurag

    (Baylor College of Medicine
    Baylor College of Medicine)

  • Malachi Griffith

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine)

  • Jingqin Luo

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Dongsheng Tu

    (University of British Columbia)

  • Belinda Yeo

    (Institute of Cancer Research)

  • Jason Kunisaki

    (Washington University School of Medicine)

  • Christopher A Miller

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Kilannin Krysiak

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Jasreet Hundal

    (Washington University School of Medicine)

  • Benjamin J Ainscough

    (Washington University School of Medicine)

  • Zachary L. Skidmore

    (Washington University School of Medicine)

  • Katie Campbell

    (Washington University School of Medicine)

  • Runjun Kumar

    (Washington University School of Medicine)

  • Catrina Fronick

    (Washington University School of Medicine)

  • Lisa Cook

    (Washington University School of Medicine)

  • Jacqueline E. Snider

    (Washington University School of Medicine)

  • Sherri Davies

    (Washington University School of Medicine)

  • Shyam M. Kavuri

    (Baylor College of Medicine
    Baylor College of Medicine)

  • Eric C. Chang

    (Baylor College of Medicine
    Baylor College of Medicine)

  • Vincent Magrini

    (Washington University School of Medicine
    Washington University School of Medicine
    The Ohio State University College of Medicine)

  • David E. Larson

    (Washington University School of Medicine)

  • Robert S Fulton

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Shuzhen Liu

    (University of British Columbia)

  • Samuel Leung

    (University of British Columbia)

  • David Voduc

    (University of British Columbia)

  • Ron Bose

    (Washington University School of Medicine)

  • Mitch Dowsett

    (Institute of Cancer Research)

  • Richard K. Wilson

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine)

  • Torsten O. Nielsen

    (University of British Columbia)

  • Elaine R Mardis

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine
    The Ohio State University College of Medicine)

  • Matthew J. Ellis

    (Baylor College of Medicine
    Baylor College of Medicine)

Abstract

Here we report targeted sequencing of 83 genes using DNA from primary breast cancer samples from 625 postmenopausal (UBC-TAM series) and 328 premenopausal (MA12 trial) hormone receptor-positive (HR+) patients to determine interactions between somatic mutation and prognosis. Independent validation of prognostic interactions was achieved using data from the METABRIC study. Previously established associations between MAP3K1 and PIK3CA mutations with luminal A status/favorable prognosis and TP53 mutations with Luminal B/non-luminal tumors/poor prognosis were observed, validating the methodological approach. In UBC-TAM, NF1 frame-shift nonsense (FS/NS) mutations were also a poor outcome driver that was validated in METABRIC. For MA12, poor outcome associated with PIK3R1 mutation was also reproducible. DDR1 mutations were strongly associated with poor prognosis in UBC-TAM despite stringent false discovery correction (q = 0.0003). In conclusion, uncommon recurrent somatic mutations should be further explored to create a more complete explanation of the highly variable outcomes that typifies ER+ breast cancer.

Suggested Citation

  • Obi L. Griffith & Nicholas C. Spies & Meenakshi Anurag & Malachi Griffith & Jingqin Luo & Dongsheng Tu & Belinda Yeo & Jason Kunisaki & Christopher A Miller & Kilannin Krysiak & Jasreet Hundal & Benja, 2018. "The prognostic effects of somatic mutations in ER-positive breast cancer," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05914-x
    DOI: 10.1038/s41467-018-05914-x
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