Discovery of naturally occurring ESR1 mutations in breast cancer cell lines modelling endocrine resistance View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Lesley-Ann Martin, Ricardo Ribas, Nikiana Simigdala, Eugene Schuster, Sunil Pancholi, Tencho Tenev, Pascal Gellert, Laki Buluwela, Alison Harrod, Allan Thornhill, Joanna Nikitorowicz-Buniak, Amandeep Bhamra, Marc-Olivier Turgeon, George Poulogiannis, Qiong Gao, Vera Martins, Margaret Hills, Isaac Garcia-Murillas, Charlotte Fribbens, Neill Patani, Zheqi Li, Matthew J. Sikora, Nicholas Turner, Wilbert Zwart, Steffi Oesterreich, Jason Carroll, Simak Ali, Mitch Dowsett

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. More... »

PAGES

1865

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-017-01864-y

    DOI

    http://dx.doi.org/10.1038/s41467-017-01864-y

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1092999883

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29192207


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