Format

Send to

Choose Destination
Nat Commun. 2019 Sep 13;10(1):4182. doi: 10.1038/s41467-019-12125-5.

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

Author information

1
Department of Medical Oncology, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA.
2
Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.
3
Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.
4
Deciphera Pharmaceuticals, Waltham, MA, USA.
5
Department of Cancer Biology, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA.
6
Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA.
7
Nagoya University Graduate School of Medicine, Nagoya, Japan.
8
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.
9
ImmunoGen, Inc, Waltham, MA, USA.
10
EMEA Site Intelligence and Activation, Tel Aviv, Israel.
11
WuXi NextCODE, Cambridge, MA, USA.
12
Department of Biomedical Engineering, Yale University, New Haven, CT, 06511, USA.
13
Second Military Medical University, Shanghai, 200433, P.R. China.
14
Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.
15
University of New Mexico School of Medicine, Albuquerque, NM, USA.
16
Lurie Family Imaging Center, Center for Biomedical Imaging in Oncology, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA.
17
Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
18
Metamark Genetics Inc, Worcester, MA, USA.
19
Baylor-Charles A. Sammons Cancer Center, Dallas, TX, 75246, USA.
20
University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 94143, USA.
21
Department of Pathology, Brigham and Women's Hospital, Boston, MA, 02115, USA.
22
Department of Pathology, Harvard Medical School, Boston, MA, 02115, USA.
23
Johns Hopkins Medical Institutions, Baltimore, MD, USA.
24
Department of Pathology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
25
Sutter Roseville Medical Center, Roseville, CA, 95661, USA.
26
Cancer Treatment Centers of America, Atlanta, GA, USA.
27
Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
28
Duke University, Durham, NC, USA.
29
Department of Data Science, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA.
30
Department of Biostatistics, Harvard T. H. Chan School of Public Health Boston, Boston, MA, 02215, USA.
31
Department of Stem Cell and Regenerative Biology, Harvard University Cambridge, Cambridge, MA, 02138, USA.
32
Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
33
MD Anderson Cancer Center, Houston, TX, 77030, USA.
34
Department of Medical Oncology, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA. Kornelia_Polyak@dfci.harvard.edu.
35
Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA. Kornelia_Polyak@dfci.harvard.edu.
36
Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA. Kornelia_Polyak@dfci.harvard.edu.
37
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA. Kornelia_Polyak@dfci.harvard.edu.
38
Harvard Stem Cell Institute, Cambridge, MA, 02138, USA. Kornelia_Polyak@dfci.harvard.edu.

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center