Skip to main content
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

  • Register
  • Log in
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in

Search

  • Advanced search
Cancer Research
Cancer Research

Advanced Search

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
Molecular and Cellular Biology, Genetics

Abstract 1033: Estrogen receptor gene fusions drive endocrine therapy resistance in estrogen receptor positive breast cancer

Jonathan T. Lei, Jieya Shao, Jin Zhang, Michael Iglesia, Doug W. Chan, Ryoichi Matsunuma, Xiaping He, Purba Singh, Yoshimasa Kosaka, Robert Crowder, Svasti Haricharan, Shyam Kavuri, Jeremy Hoog, Chanpheng Phommaly, Rodrigo Goncalves, Susana Romalho, Wei-Chu Lai, Oliver Hampton, Anna Rogers, Ethan Tobias, Poojan Parikh, Sherri Davies, Cynthia Ma, Vera Suman, Kelly Hunt, Mark Watson, Katherine A. Hoadley, Aubrey Thompson, Charles Perou, Chad J. Creighton, Chris Maher and Matthew J. Ellis
Jonathan T. Lei
Baylor College of Medicine, Houston, TX;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jieya Shao
Washington University School of Medicine in St. Louis, MO;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jin Zhang
Washington University in St. Louis, MO;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael Iglesia
University of North Carolina Chapel Hill, NC;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Doug W. Chan
Baylor College of Medicine, Houston, TX;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ryoichi Matsunuma
Baylor College of Medicine, Houston, TX;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiaping He
University of North Carolina Chapel Hill, NC;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Purba Singh
Baylor College of Medicine, Houston, TX;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yoshimasa Kosaka
Kitasato University School of Medicine, Japan;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert Crowder
Washington University School of Medicine in St. Louis, MO;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Svasti Haricharan
Baylor College of Medicine, Houston, TX;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shyam Kavuri
Baylor College of Medicine, Houston, TX;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jeremy Hoog
Washington University School of Medicine in St. Louis, MO;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chanpheng Phommaly
Washington University School of Medicine in St. Louis, MO;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rodrigo Goncalves
University of Sao Paulo School of Medicine (FMUSP), Brazil;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Susana Romalho
State University of Campinas, Brazil;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wei-Chu Lai
Washington University School of Medicine in St. Louis, MO;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Oliver Hampton
Baylor College of Medicine, Houston, TX;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anna Rogers
Washington University School of Medicine in St. Louis, MO;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ethan Tobias
Washington University School of Medicine in St. Louis, MO;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Poojan Parikh
Washington University School of Medicine in St. Louis, MO;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sherri Davies
Washington University School of Medicine in St. Louis, MO;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cynthia Ma
Washington University School of Medicine in St. Louis, MO;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vera Suman
Mayo Clinic, Rochester, MN;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kelly Hunt
MD Anderson Cancer Center, Houston, TX;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark Watson
Washington University School of Medicine in St. Louis, MO;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katherine A. Hoadley
University of North Carolina Chapel Hill, NC;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Aubrey Thompson
Mayo Clinic, Jacksonville, FL.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Charles Perou
University of North Carolina Chapel Hill, NC;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chad J. Creighton
Baylor College of Medicine, Houston, TX;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chris Maher
Washington University in St. Louis, MO;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthew J. Ellis
Baylor College of Medicine, Houston, TX;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/1538-7445.AM2017-1033 Published July 2017
  • Article
  • Info & Metrics
Loading
Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC

Abstract

Dysregulation of estrogen receptor gene (ESR1) is an established mechanism of inducing endocrine therapy resistance. We previously discovered a chromosomal translocation event generating an estrogen receptor gene fused in-frame to C-terminal sequences of YAP1 (ESR1-YAP1) that contributed to endocrine therapy resistance in estrogen receptor positive (ER+) breast cancer models. This current study compares functional and pharmacological properties of additional ESR1 gene fusion events of both early stage (ESR1-NOP2) and advanced endocrine therapy resistant (ESR1-YAP1 and ESR1-PCDH11x) breast cancers. The YAP1 and PCDH11x fusions conferred estrogen-independent and fulvestrant-resistant growth in T47D, an ER+ breast cancer cell line in vitro and in vivo, in contrast to the NOP2 fusion which was sensitive to hormone deprivation. Immunohistochemical (IHC) staining of mouse lungs revealed significantly higher numbers of micrometastatic ER+ cells from the T47D tumors expressing the YAP1 and PCDH11x fusions than YFP control and NOP2 fusion. Estrogen response element (ERE) reporter and pull down assays revealed that although all ESR1 fusions studied bound EREs, only the YAP1 and PCDH11x caused ERE activation. Cell lines containing these “canonical” ESR1 fusions upregulated expression of ER responsive genes such as TFF1 and GREB1 in hormone deprived conditions. In contrast, the NOP2 fusion neither induced ERE activity nor upregulated TFF1 and GREB1 gene expression. The proliferative ability of canonical fusion-containing T47D cells was inhibited by palbociclib, a CDK4/6 inhibitor, in a dose-dependent manner. In vivo growth of patient-derived xenograft tumors naturally harboring the ESR1-YAP1 fusion (WHIM18) was significantly reduced in mice fed palbociclib-containing chow. Mice transplanted with WHIM18 also formed lung micrometastases, with an ER IHC staining pattern similar to lungs from YAP1 and PCDH11x fusion expressing T47D xenografts. In conclusion, in-frame ERE activating canonical fusions occur in end-stage, drug resistant, advanced breast cancer and can be added to ESR1 point mutations as a class of somatic mutation that may cause acquired resistance. Endocrine therapy resistant growth induced by these fusions can be treated with CDK4/6 inhibition, using an FDA approved drug, palbociclib, which could potentially improve outcomes in patients with ESR1 translocated tumors.

Citation Format: Jonathan T. Lei, Jieya Shao, Jin Zhang, Michael Iglesia, Doug W. Chan, Ryoichi Matsunuma, Xiaping He, Purba Singh, Yoshimasa Kosaka, Robert Crowder, Svasti Haricharan, Shyam Kavuri, Jeremy Hoog, Chanpheng Phommaly, Rodrigo Goncalves, Susana Romalho, Wei-Chu Lai, Oliver Hampton, Anna Rogers, Ethan Tobias, Poojan Parikh, Sherri Davies, Cynthia Ma, Vera Suman, Kelly Hunt, Mark Watson, Katherine A. Hoadley, Aubrey Thompson, Charles Perou, Chad J. Creighton, Chris Maher, Matthew J. Ellis. Estrogen receptor gene fusions drive endocrine therapy resistance in estrogen receptor positive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1033. doi:10.1158/1538-7445.AM2017-1033

  • ©2017 American Association for Cancer Research.
Previous
Back to top
Cancer Research: 77 (13 Supplement)
July 2017
Volume 77, Issue 13 Supplement
  • Table of Contents
  • Index by Author

Sign up for alerts

Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Abstract 1033: Estrogen receptor gene fusions drive endocrine therapy resistance in estrogen receptor positive breast cancer
(Your Name) has forwarded a page to you from Cancer Research
(Your Name) thought you would be interested in this article in Cancer Research.
Citation Tools
Abstract 1033: Estrogen receptor gene fusions drive endocrine therapy resistance in estrogen receptor positive breast cancer
Jonathan T. Lei, Jieya Shao, Jin Zhang, Michael Iglesia, Doug W. Chan, Ryoichi Matsunuma, Xiaping He, Purba Singh, Yoshimasa Kosaka, Robert Crowder, Svasti Haricharan, Shyam Kavuri, Jeremy Hoog, Chanpheng Phommaly, Rodrigo Goncalves, Susana Romalho, Wei-Chu Lai, Oliver Hampton, Anna Rogers, Ethan Tobias, Poojan Parikh, Sherri Davies, Cynthia Ma, Vera Suman, Kelly Hunt, Mark Watson, Katherine A. Hoadley, Aubrey Thompson, Charles Perou, Chad J. Creighton, Chris Maher and Matthew J. Ellis
Cancer Res July 1 2017 (77) (13 Supplement) 1033; DOI: 10.1158/1538-7445.AM2017-1033

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Abstract 1033: Estrogen receptor gene fusions drive endocrine therapy resistance in estrogen receptor positive breast cancer
Jonathan T. Lei, Jieya Shao, Jin Zhang, Michael Iglesia, Doug W. Chan, Ryoichi Matsunuma, Xiaping He, Purba Singh, Yoshimasa Kosaka, Robert Crowder, Svasti Haricharan, Shyam Kavuri, Jeremy Hoog, Chanpheng Phommaly, Rodrigo Goncalves, Susana Romalho, Wei-Chu Lai, Oliver Hampton, Anna Rogers, Ethan Tobias, Poojan Parikh, Sherri Davies, Cynthia Ma, Vera Suman, Kelly Hunt, Mark Watson, Katherine A. Hoadley, Aubrey Thompson, Charles Perou, Chad J. Creighton, Chris Maher and Matthew J. Ellis
Cancer Res July 1 2017 (77) (13 Supplement) 1033; DOI: 10.1158/1538-7445.AM2017-1033
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
Advertisement

Related Articles

Cited By...

More in this TOC Section

Molecular and Cellular Biology, Genetics

  • Abstract LB-280: The landscape of somatic microsatellite indels across cancer: detection and identification of driver events
  • Abstract LB-267: Metabolic alterations in tumors cause cachexia in pancreatic cancer
  • Abstract LB-328: Mir-520b as a novel molecular target for suppressing stemness phenotype of head-neck cancer by inhibiting CD44
Show more 3

Oral Presentations - Proffered Abstracts

  • Abstract LB-338: A critical evaluation of genomic data sharing: Barriers to accessing pediatric cancer genomic datasets: a Treehouse Childhood Cancer Initiative experience
  • Abstract LB-105: Characterization of total mutational burden in the GENIE cohort: Small and large panels can provide TMB information but to varying degrees
  • Abstract LB-103: Landscape of somatic ERBB2 Mutations: Findings from AACR GENIE and comparison to ongoing ERBB2 mutant basket study
Show more 3

Proffered Oral Presentations - Oncogenes and Tumor Suppressors 1: Function and Therapeutic Vulnerabilities

  • Abstract 1030: Metabolic reprogramming caused by mutations of the Fbw7 ubiquitin ligase in colorectal cancer
  • Abstract 1028: Genetic disruption of Kras sensitizes lung cancer cells to Fas-mediated apoptosis
Show more 3
  • Home
  • Alerts
  • Feedback
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians
  • Reviewers

About Cancer Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2018 by the American Association for Cancer Research.

Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

Advertisement