Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Functional Annotation of ESR1 Gene Fusions in Estrogen Receptor-Positive Breast Cancer.

Authors: Lei, Jonathan T; Shao, Jieya; Zhang, Jin; Iglesia, Michael; Chan, Doug W; Cao, Jin; Anurag, Meenakshi; Singh, Purba; He, Xiaping; Kosaka, Yoshimasa; Matsunuma, Ryoichi; Crowder, Robert; Hoog, Jeremy; Phommaly, Chanpheng; Goncalves, Rodrigo; Ramalho, Susana; Peres, Raquel Mary Rodrigues; Punturi, Nindo; Schmidt, Cheryl; Bartram, Alex; Jou, Eric; Devarakonda, Vaishnavi; Holloway, Kimberly R; Lai, W Victoria; Hampton, Oliver; Rogers, Anna; Tobias, Ethan; Parikh, Poojan A; Davies, Sherri R; Li, Shunqiang; Ma, Cynthia X; Suman, Vera J; Hunt, Kelly K; Watson, Mark A; Hoadley, Katherine A; Thompson, E Aubrey; Chen, Xi; Kavuri, Shyam M; Creighton, Chad J; Maher, Christopher A; Perou, Charles M; Haricharan, Svasti; Ellis, Matthew J

Published In Cell Rep, (2018 08 07)

Abstract: RNA sequencing (RNA-seq) detects estrogen receptor alpha gene (ESR1) fusion transcripts in estrogen receptor-positive (ER+) breast cancer, but their role in disease pathogenesis remains unclear. We examined multiple ESR1 fusions and found that two, both identified in advanced endocrine treatment-resistant disease, encoded stable and functional fusion proteins. In both examples, ESR1-e6>YAP1 and ESR1-e6>PCDH11X, ESR1 exons 1-6 were fused in frame to C-terminal sequences from the partner gene. Functional properties include estrogen-independent growth, constitutive expression of ER target genes, and anti-estrogen resistance. Both fusions activate a metastasis-associated transcriptional program, induce cellular motility, and promote the development of lung metastasis. ESR1-e6>YAP1- and ESR1-e6>PCDH11X-induced growth remained sensitive to a CDK4/6 inhibitor, and a patient-derived xenograft (PDX) naturally expressing the ESR1-e6>YAP1 fusion was also responsive. Transcriptionally active ESR1 fusions therefore trigger both endocrine therapy resistance and metastatic progression, explaining the association with fatal disease progression, although CDK4/6 inhibitor treatment is predicted to be effective.

PubMed ID: 30089255 Exiting the NIEHS site

MeSH Terms: Breast Neoplasms/genetics*; Breast Neoplasms/pathology; Estrogen Receptor alpha/genetics*; Female; Gene Fusion/genetics*; Humans; Transfection

Back
to Top