Recurrent hormone-binding domain truncated ESR1 amplifications in primary endometrial cancers suggest their implication in hormone independent growth View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-05-10

AUTHORS

Frederik Holst, Erling A. Hoivik, William J. Gibson, Amaro Taylor-Weiner, Steven E. Schumacher, Yan W. Asmann, Patrick Grossmann, Jone Trovik, Brian M. Necela, E. Aubrey Thompson, Matthew Meyerson, Rameen Beroukhim, Helga B. Salvesen, Andrew D. Cherniack

ABSTRACT

The estrogen receptor alpha (ERα) is highly expressed in both endometrial and breast cancers, and represents the most prevalent therapeutic target in breast cancer. However, anti-estrogen therapy has not been shown to be effective in endometrial cancer. Recently it has been shown that hormone-binding domain alterations of ERα in breast cancer contribute to acquired resistance to anti-estrogen therapy. In analyses of genomic data from The Cancer Genome Atlas (TCGA), we observe that endometrial carcinomas manifest recurrent ESR1 gene amplifications that truncate the hormone-binding domain encoding region of ESR1 and are associated with reduced mRNA expression of exons encoding the hormone-binding domain. These findings support a role for hormone-binding alterations of ERα in primary endometrial cancer, with potentially important therapeutic implications. More... »

PAGES

25521

References to SciGraph publications

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  • 2011-07-22. The different roles of ER subtypes in cancer biology and therapy in NATURE REVIEWS CANCER
  • 2000-08. Formation of a powerful capping motif corresponding to start of “helix 12” in agonist-bound estrogen receptor-α contributes to increased constitutive activity of the protein in CELL BIOCHEMISTRY AND BIOPHYSICS
  • 2013-11-03. Activating ESR1 mutations in hormone-resistant metastatic breast cancer in NATURE GENETICS
  • 2010-02. The landscape of somatic copy-number alteration across human cancers in NATURE
  • 2010-03-25. Identification of novel transcript variants of estrogen receptor α, β and progesterone receptor gene in human endometrium in ENDOCRINE
  • 2013-09-26. Pan-cancer patterns of somatic copy number alteration in NATURE GENETICS
  • 2008-05-30. Mapping and quantifying mammalian transcriptomes by RNA-Seq in NATURE METHODS
  • 2013-05-01. Integrated genomic characterization of endometrial carcinoma in NATURE
  • 2014-08-07. Recurrent ESR1–CCDC170 rearrangements in an aggressive subset of oestrogen receptor-positive breast cancers in NATURE COMMUNICATIONS
  • 2014-02-01. Estrogen receptor (ER) α mutations in breast cancer: hidden in plain sight in BREAST CANCER RESEARCH AND TREATMENT
  • 2014-02-05. Examestane in advanced or recurrent endometrial carcinoma: a prospective phase II study by the Nordic Society of Gynecologic Oncology (NSGO) in BMC CANCER
  • 2011-01-01. Integrative genomics viewer in NATURE BIOTECHNOLOGY
  • 2011-04-28. GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers in GENOME BIOLOGY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/srep25521

    DOI

    http://dx.doi.org/10.1038/srep25521

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1038848024

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27160768


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    20 schema:description The estrogen receptor alpha (ERα) is highly expressed in both endometrial and breast cancers, and represents the most prevalent therapeutic target in breast cancer. However, anti-estrogen therapy has not been shown to be effective in endometrial cancer. Recently it has been shown that hormone-binding domain alterations of ERα in breast cancer contribute to acquired resistance to anti-estrogen therapy. In analyses of genomic data from The Cancer Genome Atlas (TCGA), we observe that endometrial carcinomas manifest recurrent ESR1 gene amplifications that truncate the hormone-binding domain encoding region of ESR1 and are associated with reduced mRNA expression of exons encoding the hormone-binding domain. These findings support a role for hormone-binding alterations of ERα in primary endometrial cancer, with potentially important therapeutic implications.
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