title: Recurrent hormone-binding domain truncated ESR1 amplifications in primary endometrial cancers suggest their implication in hormone independent growth.
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.
authors.affiliation: Centre for Cancer Biomarkers, Department of Clinical Science, The University of Bergen, Norway.|KG Jebsen Center for Precision Medicine in Gynecologic Cancer, Department of Gynecology and Obstetrics, Haukeland University Hospital Bergen, Norway.|Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
authors.forename: Frederik
authors.initials: F
authors.lastname: Holst
authors.affiliation: Centre for Cancer Biomarkers, Department of Clinical Science, The University of Bergen, Norway.|KG Jebsen Center for Precision Medicine in Gynecologic Cancer, Department of Gynecology and Obstetrics, Haukeland University Hospital Bergen, Norway.
authors.forename: Erling A
authors.initials: EA
authors.lastname: Hoivik
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Gibson
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Amaro
authors.initials: A
authors.lastname: Taylor-Weiner
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Schumacher
authors.affiliation: Department of Health Sciences Research, Mayo Clinic Cancer Center, Jacksonville, Florida 32224, USA.
authors.forename: Yan W
authors.initials: YW
authors.lastname: Asmann
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.|Department of Biostatistics &Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Grossmann
authors.affiliation: Centre for Cancer Biomarkers, Department of Clinical Science, The University of Bergen, Norway.|KG Jebsen Center for Precision Medicine in Gynecologic Cancer, Department of Gynecology and Obstetrics, Haukeland University Hospital Bergen, Norway.
authors.forename: Jone
authors.initials: J
authors.lastname: Trovik
authors.affiliation: Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, Florida.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Necela
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: E Aubrey
authors.initials: EA
authors.lastname: Thompson
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Rameen
authors.initials: R
authors.lastname: Beroukhim
authors.affiliation: Centre for Cancer Biomarkers, Department of Clinical Science, The University of Bergen, Norway.|KG Jebsen Center for Precision Medicine in Gynecologic Cancer, Department of Gynecology and Obstetrics, Haukeland University Hospital Bergen, Norway.
authors.forename: Helga B
authors.initials: HB
authors.lastname: Salvesen
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Cherniack