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Whole-genome analysis informs breast cancer response to aromatase inhibition

Author

Listed:
  • Matthew J. Ellis

    (Washington University
    Siteman Cancer Center, Washington University
    Breast Cancer Program, Washington University)

  • Li Ding

    (The Genome Institute, Washington University
    Washington University)

  • Dong Shen

    (The Genome Institute, Washington University
    Washington University)

  • Jingqin Luo

    (Breast Cancer Program, Washington University
    Washington University)

  • Vera J. Suman

    (ACOSOG Statistical Center, Mayo Clinic)

  • John W. Wallis

    (The Genome Institute, Washington University
    Washington University)

  • Brian A. Van Tine

    (Washington University)

  • Jeremy Hoog

    (Washington University)

  • Reece J. Goiffon

    (BRIGHT Institute, Washington University School of Medicine
    Molecular Imaging Center, Washington University
    Malinckrodt Institute of Radiology, Washington University)

  • Theodore C. Goldstein

    (University of California)

  • Sam Ng

    (University of California)

  • Li Lin

    (Washington University)

  • Robert Crowder

    (Washington University)

  • Jacqueline Snider

    (Washington University)

  • Karla Ballman

    (ACOSOG Statistical Center, Mayo Clinic)

  • Jason Weber

    (Washington University
    BRIGHT Institute, Washington University School of Medicine
    Washington University)

  • Ken Chen

    (M. D. Anderson Cancer Center)

  • Daniel C. Koboldt

    (The Genome Institute, Washington University
    Washington University)

  • Cyriac Kandoth

    (The Genome Institute, Washington University
    Washington University)

  • William S. Schierding

    (The Genome Institute, Washington University
    Washington University)

  • Joshua F. McMichael

    (The Genome Institute, Washington University
    Washington University)

  • Christopher A. Miller

    (The Genome Institute, Washington University
    Washington University)

  • Charles Lu

    (The Genome Institute, Washington University
    Washington University)

  • Christopher C. Harris

    (The Genome Institute, Washington University
    Washington University)

  • Michael D. McLellan

    (The Genome Institute, Washington University
    Washington University)

  • Michael C. Wendl

    (The Genome Institute, Washington University
    Washington University)

  • Katherine DeSchryver

    (Washington University)

  • D. Craig Allred

    (Breast Cancer Program, Washington University
    Washington University)

  • Laura Esserman

    (Helen Diller Cancer Center, University of California)

  • Gary Unzeitig

    (Doctors Hospital of Laredo)

  • Julie Margenthaler

    (Siteman Cancer Center, Washington University)

  • G. V. Babiera

    (M. D. Anderson Cancer Center)

  • P. Kelly Marcom

    (Duke University Cancer Center)

  • J. M. Guenther

    (Good Samaritan Hospital)

  • Marilyn Leitch

    (Simmons Cancer Center, University of Texas Southwestern)

  • Kelly Hunt

    (M. D. Anderson Cancer Center)

  • John Olson

    (Duke University Cancer Center)

  • Yu Tao

    (Washington University)

  • Christopher A. Maher

    (Washington University
    The Genome Institute, Washington University)

  • Lucinda L. Fulton

    (The Genome Institute, Washington University
    Washington University)

  • Robert S. Fulton

    (The Genome Institute, Washington University
    Washington University)

  • Michelle Harrison

    (The Genome Institute, Washington University
    Washington University)

  • Ben Oberkfell

    (The Genome Institute, Washington University
    Washington University)

  • Feiyu Du

    (The Genome Institute, Washington University
    Washington University)

  • Ryan Demeter

    (The Genome Institute, Washington University
    Washington University)

  • Tammi L. Vickery

    (The Genome Institute, Washington University
    Washington University)

  • Adnan Elhammali

    (BRIGHT Institute, Washington University School of Medicine
    Molecular Imaging Center, Washington University
    Malinckrodt Institute of Radiology, Washington University)

  • Helen Piwnica-Worms

    (BRIGHT Institute, Washington University School of Medicine
    Washington University
    Washington University
    Howard Hughes Medical Institute)

  • Sandra McDonald

    (Siteman Cancer Center, Washington University
    ACOSOG Central Specimen Bank, Washington University)

  • Mark Watson

    (Washington University
    Washington University
    ACOSOG Central Specimen Bank, Washington University)

  • David J. Dooling

    (The Genome Institute, Washington University
    Washington University)

  • David Ota

    (ACOSOG Operations Center, Duke University)

  • Li-Wei Chang

    (Breast Cancer Program, Washington University
    Washington University)

  • Ron Bose

    (Siteman Cancer Center, Washington University
    Breast Cancer Program, Washington University)

  • Timothy J. Ley

    (Washington University
    Siteman Cancer Center, Washington University
    The Genome Institute, Washington University)

  • David Piwnica-Worms

    (BRIGHT Institute, Washington University School of Medicine
    Molecular Imaging Center, Washington University
    Malinckrodt Institute of Radiology, Washington University
    Washington University)

  • Joshua M. Stuart

    (University of California)

  • Richard K. Wilson

    (Siteman Cancer Center, Washington University
    The Genome Institute, Washington University
    Washington University)

  • Elaine R. Mardis

    (Siteman Cancer Center, Washington University
    The Genome Institute, Washington University
    Washington University)

Abstract

To correlate the variable clinical features of oestrogen-receptor-positive breast cancer with somatic alterations, we studied pretreatment tumour biopsies accrued from patients in two studies of neoadjuvant aromatase inhibitor therapy by massively parallel sequencing and analysis. Eighteen significantly mutated genes were identified, including five genes (RUNX1, CBFB, MYH9, MLL3 and SF3B1) previously linked to haematopoietic disorders. Mutant MAP3K1 was associated with luminal A status, low-grade histology and low proliferation rates, whereas mutant TP53 was associated with the opposite pattern. Moreover, mutant GATA3 correlated with suppression of proliferation upon aromatase inhibitor treatment. Pathway analysis demonstrated that mutations in MAP2K4, a MAP3K1 substrate, produced similar perturbations as MAP3K1 loss. Distinct phenotypes in oestrogen-receptor-positive breast cancer are associated with specific patterns of somatic mutations that map into cellular pathways linked to tumour biology, but most recurrent mutations are relatively infrequent. Prospective clinical trials based on these findings will require comprehensive genome sequencing.

Suggested Citation

  • Matthew J. Ellis & Li Ding & Dong Shen & Jingqin Luo & Vera J. Suman & John W. Wallis & Brian A. Van Tine & Jeremy Hoog & Reece J. Goiffon & Theodore C. Goldstein & Sam Ng & Li Lin & Robert Crowder & , 2012. "Whole-genome analysis informs breast cancer response to aromatase inhibition," Nature, Nature, vol. 486(7403), pages 353-360, June.
    • Handle: RePEc:nat:nature:v:486:y:2012:i:7403:d:10.1038_nature11143
    DOI: 10.1038/nature11143
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    Cited by:

    1. Zhe Jiang & YoungJun Ju & Amjad Ali & Philip E. D. Chung & Patryk Skowron & Dong-Yu Wang & Mariusz Shrestha & Huiqin Li & Jeff C. Liu & Ioulia Vorobieva & Ronak Ghanbari-Azarnier & Ethel Mwewa & Maria, 2023. "Distinct shared and compartment-enriched oncogenic networks drive primary versus metastatic breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    2. Nathalie Beaufort & Linda Ingendahl & Melisa Merdanovic & Andree Schmidt & David Podlesainski & Tim Richter & Thorben Neumann & Michael Kuszner & Ingrid R. Vetter & Patricia Stege & Steven G. Burston , 2024. "Rational correction of pathogenic conformational defects in HTRA1," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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