Discovery of naturally occurring ESR1 mutations in breast cancer cell lines modelling endocrine resistance.

File Description SizeFormat 
Martin_et_al-2017-Nature_Communications.pdfPublished version2.42 MBAdobe PDFDownload
Title: Discovery of naturally occurring ESR1 mutations in breast cancer cell lines modelling endocrine resistance.
Author(s): Martin, L-A
Ribas, R
Simigdala, N
Schuster, E
Pancholi, S
Tenev, T
Gellert, P
Buluwela, L
Harrod, A
Thornhill, A
Nikitorowicz-Buniak, J
Bhamra, A
Turgeon, M-O
Poulogiannis, G
Gao, Q
Martins, V
Hills, M
Garcia-Murillas, I
Fribbens, C
Patani, N
Li, Z
Sikora, MJ
Turner, N
Zwart, W
Oesterreich, S
Carroll, J
Ali, S
Dowsett, M
Item Type: Journal Article
Abstract: Resistance to endocrine therapy remains a major clinical problem in breast cancer. Genetic studies highlight the potential role of estrogen receptor-α (ESR1) mutations, which show increased prevalence in the metastatic, endocrine-resistant setting. No naturally occurring ESR1 mutations have been reported in in vitro models of BC either before or after the acquisition of endocrine resistance making functional consequences difficult to study. We report the first discovery of naturally occurring ESR1 Y537C and ESR1 Y537S mutations in MCF7 and SUM44 ESR1-positive cell lines after acquisition of resistance to long-term-estrogen-deprivation (LTED) and subsequent resistance to fulvestrant (ICIR). Mutations were enriched with time, impacted on ESR1 binding to the genome and altered the ESR1 interactome. The results highlight the importance and functional consequence of these mutations and provide an important resource for studying endocrine resistance.
Publication Date: 30-Nov-2017
Date of Acceptance: 20-Oct-2017
URI: http://hdl.handle.net/10044/1/54932
DOI: https://dx.doi.org/10.1038/s41467-017-01864-y
ISSN: 2041-1723
Publisher: Nature Publishing Group
Journal / Book Title: Nature Communications
Volume: 8
Issue: 1
Copyright Statement: This article is licensed under a Creative CommonsAttribution 4.0 International License, which permits use, sharing,adaptation, distribution and reproduction in any medium or format, as long as you giveappropriate credit to the original author(s) and the source, provide a link to the CreativeCommons license, and indicate if changes were made. The images or other third partymaterial in this article are included in the article’s Creative Commons license, unlessindicated otherwise in a credit line to the material. If material is not included in thearticle’s Creative Commons license and your intended use is not permitted by statutoryregulation or exceeds the permitted use, you will need to obtain permission directly fromthe copyright holder. To view a copy of this license, visithttp://creativecommons.org/licenses/by/4.0/.© The Author(s) 2017
Keywords: MD Multidisciplinary
Publication Status: Published
Article Number: 1865
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



Items in Spiral are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commons