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

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, Maša Alečković, Carlos Gil del Alcazar, Ryan J. Caulfield, Dennis M. Bonal, Quang- De Nguyen, Vanessa F. Merino, Sibgat Choudhury, Gabrielle Ethington, Laura Panos, Michael Grant, William Herlihy, Alfred Au, Gedge D. Rosson, Pedram Argani, Andrea L. Richardson, Deborah Dillon, D. Craig Allred, Kirsten Babski, Elizabeth Min Hui Kim, Charles H. McDonnell, Jon Wagner, Ron Rowberry, Kristie Bobolis, Celina G. Kleer, E. Shelley Hwang, Joanne L. Blum, Simona Cristea, Piotr Sicinski, Rong Fan, Henry W. Long, Saraswati Sukumar, So Yeon Park, Judy E. Garber, Mina Bissell, Jun Yao and Kornelia Polyak ()
Additional contact information
Lina Ding: Dana-Farber Cancer Institute Boston
Ying Su: Dana-Farber Cancer Institute Boston
Anne Fassl: Dana-Farber Cancer Institute Boston
Kunihiko Hinohara: Dana-Farber Cancer Institute Boston
Xintao Qiu: Dana-Farber Cancer Institute
Nicholas W. Harper: Dana-Farber Cancer Institute Boston
Sung Jin Huh: Dana-Farber Cancer Institute Boston
Noga Bloushtain-Qimron: Dana-Farber Cancer Institute Boston
Bojana Jovanović: Dana-Farber Cancer Institute Boston
Muhammad Ekram: Dana-Farber Cancer Institute Boston
Xiaoyuan Zi: Yale University
William C. Hines: Lawrence Berkeley National Laboratory
Maša Alečković: Dana-Farber Cancer Institute Boston
Carlos Gil del Alcazar: Dana-Farber Cancer Institute Boston
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
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
Deborah Dillon: Brigham and Women’s Hospital
D. Craig Allred: Washington University School of Medicine
Kirsten Babski: Sutter Roseville Medical Center
Elizabeth Min Hui Kim: Sutter Roseville Medical Center
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
Joanne L. Blum: Baylor-Charles A. Sammons Cancer Center
Simona Cristea: Dana-Farber Cancer Institute Boston
Piotr Sicinski: Dana-Farber Cancer Institute Boston
Rong Fan: Yale University
Henry W. Long: Dana-Farber Cancer Institute Boston
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
Mina Bissell: Lawrence Berkeley National Laboratory
Jun Yao: MD Anderson Cancer Center
Kornelia Polyak: Dana-Farber Cancer Institute Boston

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-12125-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12125-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-12125-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().