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; Kornelia Polyak

doi:10.1038/s41467-019-12125-5

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 EthingtonLaura 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, Kornelia Polyak

Molecular & Cellular Oncology

Research output: Contribution to journal › Article › peer-review

37 Scopus citations

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.

Original language	English (US)
Article number	4182
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-12125-5
State	Published - Dec 1 2019

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Ding, L., Su, Y., Fassl, A., Hinohara, K., Qiu, X., Harper, N. W., Huh, S. J., Bloushtain-Qimron, N., Jovanović, B., Ekram, M., Zi, X., Hines, W. C., Alečković, M., Gil del Alcazar, C., Caulfield, R. J., Bonal, D. M., Nguyen, Q. D., Merino, V. F., Choudhury, S., ... Polyak, K. (2019). Perturbed myoepithelial cell differentiation in BRCA mutation carriers and in ductal carcinoma in situ. Nature communications, 10(1), Article 4182. https://doi.org/10.1038/s41467-019-12125-5

Ding, L, Su, Y, Fassl, A, Hinohara, K, Qiu, X, Harper, NW, Huh, SJ, Bloushtain-Qimron, N, Jovanović, B, Ekram, M, Zi, X, Hines, WC, Alečković, M, Gil del Alcazar, C, Caulfield, RJ, Bonal, DM, Nguyen, QD, Merino, VF, Choudhury, S, Ethington, G, Panos, L, Grant, M, Herlihy, W, Au, A, Rosson, GD, Argani, P, Richardson, AL, Dillon, D, Allred, DC, Babski, K, Kim, EMH, McDonnell, CH, Wagner, J, Rowberry, R, Bobolis, K, Kleer, CG, Hwang, ES, Blum, JL, Cristea, S, Sicinski, P, Fan, R, Long, HW, Sukumar, S, Yeon Park, S, Garber, JE, Bissell, M, Yao, J & Polyak, K 2019, 'Perturbed myoepithelial cell differentiation in BRCA mutation carriers and in ductal carcinoma in situ', Nature communications, vol. 10, no. 1, 4182. https://doi.org/10.1038/s41467-019-12125-5

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title = "Perturbed myoepithelial cell differentiation in BRCA mutation carriers and in ductal carcinoma in situ",

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.",

author = "Lina Ding and Ying Su and Anne Fassl and Kunihiko Hinohara and Xintao Qiu and Harper, {Nicholas W.} and Huh, {Sung Jin} and Noga Bloushtain-Qimron and Bojana Jovanovi{\'c} and Muhammad Ekram and Xiaoyuan Zi and Hines, {William C.} and Ma{\v s}a Ale{\v c}kovi{\'c} and {Gil del Alcazar}, Carlos and Caulfield, {Ryan J.} and Bonal, {Dennis M.} and Nguyen, {Quang De} and Merino, {Vanessa F.} and Sibgat Choudhury and Gabrielle Ethington and Laura Panos and Michael Grant and William Herlihy and Alfred Au and Rosson, {Gedge D.} and Pedram Argani and Richardson, {Andrea L.} and Deborah Dillon and Allred, {D. Craig} and Kirsten Babski and Kim, {Elizabeth Min Hui} and McDonnell, {Charles H.} and Jon Wagner and Ron Rowberry and Kristie Bobolis and Kleer, {Celina G.} and Hwang, {E. Shelley} and Blum, {Joanne L.} and Simona Cristea and Piotr Sicinski and Rong Fan and Long, {Henry W.} and Saraswati Sukumar and {Yeon Park}, So and Garber, {Judy E.} and Mina Bissell and Jun Yao and Kornelia Polyak",

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T1 - Perturbed myoepithelial cell differentiation in BRCA mutation carriers and in ductal carcinoma in situ

AU - Ding, Lina

AU - Su, Ying

AU - Fassl, Anne

AU - Hinohara, Kunihiko

AU - Qiu, Xintao

AU - Harper, Nicholas W.

AU - Huh, Sung Jin

AU - Bloushtain-Qimron, Noga

AU - Jovanović, Bojana

AU - Ekram, Muhammad

AU - Zi, Xiaoyuan

AU - Hines, William C.

AU - Alečković, Maša

AU - Gil del Alcazar, Carlos

AU - Caulfield, Ryan J.

AU - Bonal, Dennis M.

AU - Nguyen, Quang De

AU - Merino, Vanessa F.

AU - Choudhury, Sibgat

AU - Ethington, Gabrielle

AU - Panos, Laura

AU - Grant, Michael

AU - Herlihy, William

AU - Au, Alfred

AU - Rosson, Gedge D.

AU - Argani, Pedram

AU - Richardson, Andrea L.

AU - Dillon, Deborah

AU - Allred, D. Craig

AU - Babski, Kirsten

AU - Kim, Elizabeth Min Hui

AU - McDonnell, Charles H.

AU - Wagner, Jon

AU - Rowberry, Ron

AU - Bobolis, Kristie

AU - Kleer, Celina G.

AU - Hwang, E. Shelley

AU - Blum, Joanne L.

AU - Cristea, Simona

AU - Sicinski, Piotr

AU - Fan, Rong

AU - Long, Henry W.

AU - Sukumar, Saraswati

AU - Yeon Park, So

AU - Garber, Judy E.

AU - Bissell, Mina

AU - Yao, Jun

AU - Polyak, Kornelia

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

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JO - Nature communications

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ER -

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

Abstract

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