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

Autor: Ding L; Department of Medical Oncology, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA.; Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.; Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA., Su Y; Department of Medical Oncology, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA.; Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.; Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.; Deciphera Pharmaceuticals, Waltham, MA, USA., Fassl A; Department of Cancer Biology, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA.; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA., Hinohara K; Department of Medical Oncology, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA.; Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.; Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.; Nagoya University Graduate School of Medicine, Nagoya, Japan., Qiu X; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA., Harper NW; Department of Medical Oncology, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA., Huh SJ; Department of Medical Oncology, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA.; Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.; Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.; ImmunoGen, Inc, Waltham, MA, USA., Bloushtain-Qimron N; Department of Medical Oncology, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA.; EMEA Site Intelligence and Activation, Tel Aviv, Israel., Jovanović B; Department of Medical Oncology, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA.; Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.; Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA., Ekram M; Department of Medical Oncology, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA.; Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.; Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.; WuXi NextCODE, Cambridge, MA, USA., Zi X; Department of Biomedical Engineering, Yale University, New Haven, CT, 06511, USA.; Second Military Medical University, Shanghai, 200433, P.R. China., Hines WC; Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.; University of New Mexico School of Medicine, Albuquerque, NM, USA., Alečković M; Department of Medical Oncology, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA.; Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.; Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA., Gil Del Alcazar C; Department of Medical Oncology, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA.; Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.; Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA., Caulfield RJ; Lurie Family Imaging Center, Center for Biomedical Imaging in Oncology, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA., Bonal DM; Lurie Family Imaging Center, Center for Biomedical Imaging in Oncology, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA., Nguyen QD; Lurie Family Imaging Center, Center for Biomedical Imaging in Oncology, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA., Merino VF; Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA., Choudhury S; Department of Medical Oncology, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA.; Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.; Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.; Metamark Genetics Inc, Worcester, MA, USA., Ethington G; Baylor-Charles A. Sammons Cancer Center, Dallas, TX, 75246, USA., Panos L; Baylor-Charles A. Sammons Cancer Center, Dallas, TX, 75246, USA., Grant M; Baylor-Charles A. Sammons Cancer Center, Dallas, TX, 75246, USA., Herlihy W; Baylor-Charles A. Sammons Cancer Center, Dallas, TX, 75246, USA., Au A; University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 94143, USA., Rosson GD; Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA., Argani P; Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA., Richardson AL; Department of Pathology, Brigham and Women's Hospital, Boston, MA, 02115, USA.; Department of Pathology, Harvard Medical School, Boston, MA, 02115, USA.; Johns Hopkins Medical Institutions, Baltimore, MD, USA., Dillon D; Department of Pathology, Brigham and Women's Hospital, Boston, MA, 02115, USA.; Department of Pathology, Harvard Medical School, Boston, MA, 02115, USA., Allred DC; Department of Pathology, Washington University School of Medicine, St. Louis, MO, 63110, USA., Babski K; Sutter Roseville Medical Center, Roseville, CA, 95661, USA., Kim EMH; Sutter Roseville Medical Center, Roseville, CA, 95661, USA.; Cancer Treatment Centers of America, Atlanta, GA, USA., McDonnell CH 3rd; Sutter Roseville Medical Center, Roseville, CA, 95661, USA., Wagner J; Sutter Roseville Medical Center, Roseville, CA, 95661, USA., Rowberry R; Sutter Roseville Medical Center, Roseville, CA, 95661, USA., Bobolis K; Sutter Roseville Medical Center, Roseville, CA, 95661, USA., Kleer CG; Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA., Hwang ES; University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 94143, USA.; Duke University, Durham, NC, USA., Blum JL; Baylor-Charles A. Sammons Cancer Center, Dallas, TX, 75246, USA., Cristea S; Department of Data Science, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA.; Department of Biostatistics, Harvard T. H. Chan School of Public Health Boston, Boston, MA, 02215, USA.; Department of Stem Cell and Regenerative Biology, Harvard University Cambridge, Cambridge, MA, 02138, USA., Sicinski P; Department of Cancer Biology, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA.; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA., Fan R; Department of Biomedical Engineering, Yale University, New Haven, CT, 06511, USA., Long HW; Department of Medical Oncology, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA.; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA., Sukumar S; Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA., Park SY; Department of Pathology, Seoul National University College of Medicine, Seoul, Korea., Garber JE; Department of Medical Oncology, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA.; Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.; Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA., Bissell M; Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA., Yao J; MD Anderson Cancer Center, Houston, TX, 77030, USA., Polyak K; Department of Medical Oncology, Dana-Farber Cancer Institute Boston, Boston, MA, 02215, USA. Kornelia_Polyak@dfci.harvard.edu.; Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA. Kornelia_Polyak@dfci.harvard.edu.; Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA. Kornelia_Polyak@dfci.harvard.edu.; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA. Kornelia_Polyak@dfci.harvard.edu.; Harvard Stem Cell Institute, Cambridge, MA, 02138, USA. Kornelia_Polyak@dfci.harvard.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2019 Sep 13; Vol. 10 (1), pp. 4182. Date of Electronic Publication: 2019 Sep 13.
DOI: 10.1038/s41467-019-12125-5
Abstrakt: 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.
Databáze: MEDLINE