IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-12125-5.html
   My bibliography  Save this article

Perturbed myoepithelial cell differentiation in BRCA mutation carriers and in ductal carcinoma in situ

Author

Listed:
  • Lina Ding

    (Dana-Farber Cancer Institute Boston
    Brigham and Women’s Hospital
    Harvard Medical School)

  • Ying Su

    (Dana-Farber Cancer Institute Boston
    Brigham and Women’s Hospital
    Harvard Medical School
    Deciphera Pharmaceuticals)

  • Anne Fassl

    (Dana-Farber Cancer Institute Boston
    Harvard Medical School)

  • Kunihiko Hinohara

    (Dana-Farber Cancer Institute Boston
    Brigham and Women’s Hospital
    Harvard Medical School
    Nagoya University Graduate School of Medicine)

  • Xintao Qiu

    (Dana-Farber Cancer Institute)

  • Nicholas W. Harper

    (Dana-Farber Cancer Institute Boston)

  • Sung Jin Huh

    (Dana-Farber Cancer Institute Boston
    Brigham and Women’s Hospital
    Harvard Medical School
    ImmunoGen, Inc)

  • Noga Bloushtain-Qimron

    (Dana-Farber Cancer Institute Boston
    EMEA Site Intelligence and Activation)

  • Bojana Jovanović

    (Dana-Farber Cancer Institute Boston
    Brigham and Women’s Hospital
    Harvard Medical School)

  • Muhammad Ekram

    (Dana-Farber Cancer Institute Boston
    Brigham and Women’s Hospital
    Harvard Medical School
    WuXi NextCODE)

  • Xiaoyuan Zi

    (Yale University
    Second Military Medical University)

  • William C. Hines

    (Lawrence Berkeley National Laboratory
    University of New Mexico School of Medicine)

  • Maša Alečković

    (Dana-Farber Cancer Institute Boston
    Brigham and Women’s Hospital
    Harvard Medical School)

  • Carlos Gil del Alcazar

    (Dana-Farber Cancer Institute Boston
    Brigham and Women’s Hospital
    Harvard Medical School)

  • Ryan J. Caulfield

    (Dana-Farber Cancer Institute Boston)

  • Dennis M. Bonal

    (Dana-Farber Cancer Institute Boston)

  • Quang-De Nguyen

    (Dana-Farber Cancer Institute Boston)

  • Vanessa F. Merino

    (Johns Hopkins University School of Medicine)

  • Sibgat Choudhury

    (Dana-Farber Cancer Institute Boston
    Brigham and Women’s Hospital
    Harvard Medical School
    Metamark Genetics Inc)

  • Gabrielle Ethington

    (Baylor-Charles A. Sammons Cancer Center)

  • Laura Panos

    (Baylor-Charles A. Sammons Cancer Center)

  • Michael Grant

    (Baylor-Charles A. Sammons Cancer Center)

  • William Herlihy

    (Baylor-Charles A. Sammons Cancer Center)

  • Alfred Au

    (University of California San Francisco Helen Diller Family Comprehensive Cancer Center)

  • Gedge D. Rosson

    (Johns Hopkins University School of Medicine)

  • Pedram Argani

    (Johns Hopkins University School of Medicine)

  • Andrea L. Richardson

    (Brigham and Women’s Hospital
    Harvard Medical School
    Johns Hopkins Medical Institutions)

  • Deborah Dillon

    (Brigham and Women’s Hospital
    Harvard Medical School)

  • D. Craig Allred

    (Washington University School of Medicine)

  • Kirsten Babski

    (Sutter Roseville Medical Center)

  • Elizabeth Min Hui Kim

    (Sutter Roseville Medical Center
    Cancer Treatment Centers of America)

  • Charles H. McDonnell

    (Sutter Roseville Medical Center)

  • Jon Wagner

    (Sutter Roseville Medical Center)

  • Ron Rowberry

    (Sutter Roseville Medical Center)

  • Kristie Bobolis

    (Sutter Roseville Medical Center)

  • Celina G. Kleer

    (University of Michigan)

  • E. Shelley Hwang

    (University of California San Francisco Helen Diller Family Comprehensive Cancer Center
    Duke University)

  • Joanne L. Blum

    (Baylor-Charles A. Sammons Cancer Center)

  • Simona Cristea

    (Dana-Farber Cancer Institute Boston
    Harvard T. H. Chan School of Public Health Boston
    Harvard University Cambridge)

  • Piotr Sicinski

    (Dana-Farber Cancer Institute Boston
    Harvard Medical School)

  • Rong Fan

    (Yale University)

  • Henry W. Long

    (Dana-Farber Cancer Institute Boston
    Dana-Farber Cancer Institute)

  • Saraswati Sukumar

    (Johns Hopkins University School of Medicine)

  • So Yeon Park

    (Seoul National University College of Medicine)

  • Judy E. Garber

    (Dana-Farber Cancer Institute Boston
    Brigham and Women’s Hospital
    Harvard Medical School)

  • Mina Bissell

    (Lawrence Berkeley National Laboratory)

  • Jun Yao

    (MD Anderson Cancer Center)

  • Kornelia Polyak

    (Dana-Farber Cancer Institute Boston
    Brigham and Women’s Hospital
    Harvard Medical School
    Dana-Farber Cancer Institute)

Abstract

Myoepithelial cells play key roles in normal mammary gland development and in limiting pre-invasive to invasive breast tumor progression, yet their differentiation and perturbation in ductal carcinoma in situ (DCIS) are poorly understood. Here, we investigated myoepithelial cells in normal breast tissues of BRCA1 and BRCA2 germline mutation carriers and in non-carrier controls, and in sporadic DCIS. We found that in the normal breast of non-carriers, myoepithelial cells frequently co-express the p63 and TCF7 transcription factors and that p63 and TCF7 show overlapping chromatin peaks associated with differentiated myoepithelium-specific genes. In contrast, in normal breast tissues of BRCA1 mutation carriers the frequency of p63+TCF7+ myoepithelial cells is significantly decreased and p63 and TCF7 chromatin peaks do not overlap. These myoepithelial perturbations in normal breast tissues of BRCA1 germline mutation carriers may play a role in their higher risk of breast cancer. The fraction of p63+TCF7+ myoepithelial cells is also significantly decreased in DCIS, which may be associated with invasive progression.

Suggested Citation

  • Lina Ding & Ying Su & Anne Fassl & Kunihiko Hinohara & Xintao Qiu & Nicholas W. Harper & Sung Jin Huh & Noga Bloushtain-Qimron & Bojana Jovanović & Muhammad Ekram & Xiaoyuan Zi & William C. Hines & Ma, 2019. "Perturbed myoepithelial cell differentiation in BRCA mutation carriers and in ductal carcinoma in situ," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12125-5
    DOI: 10.1038/s41467-019-12125-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-12125-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-12125-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Maryam Ghaderi Najafabadi & G. Kenneth Gray & Li Ren Kong & Komal Gupta & David Perera & Huw Naylor & Joan S. Brugge & Ashok R. Venkitaraman & Mona Shehata, 2023. "A transcriptional response to replication stress selectively expands a subset of Brca2-mutant mammary epithelial cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Vincent Geldhof & Laura P. M. H. Rooij & Liliana Sokol & Jacob Amersfoort & Maxim Schepper & Katerina Rohlenova & Griet Hoste & Adriaan Vanderstichele & Anne-Marie Delsupehe & Edoardo Isnaldi & Naima , 2022. "Single cell atlas identifies lipid-processing and immunomodulatory endothelial cells in healthy and malignant breast," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12125-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.