title: Principles Governing A-to-I RNA Editing in the Breast Cancer Transcriptome.
abstract: Little is known about how RNA editing operates in cancer. Transcriptome analysis of 68 normal and cancerous breast tissues revealed that the editing enzyme ADAR acts uniformly, on the same loci, across tissues. In controlled ADAR expression experiments, the editing frequency increased at all loci with ADAR expression levels according to the logistic model. Loci-specific "editabilities," i.e., propensities to be edited by ADAR, were quantifiable by fitting the logistic function to dose-response data. The editing frequency was increased in tumor cells in comparison to normal controls. Type I interferon response and ADAR DNA copy number together explained 53% of ADAR expression variance in breast cancers. ADAR silencing using small hairpin RNA lentivirus transduction in breast cancer cell lines led to less cell proliferation and more apoptosis. A-to-I editing is a pervasive, yet reproducible, source of variation that is globally controlled by 1q amplification and inflammation, both of which are highly prevalent among human cancers.
authors.affiliation: Breast Cancer Translational Research Laboratory, Jules Bordet Institute, Université Libre de Bruxelles (ULB), Boulevard de Waterloo, 125-1000 Brussels, Belgium.
authors.forename: Debora
authors.initials: D
authors.lastname: Fumagalli
authors.affiliation: IRIBHM, Université Libre de Bruxelles (ULB), Route de Lennik, 808-1070 Brussels, Belgium.
authors.forename: David
authors.initials: D
authors.lastname: Gacquer
authors.affiliation: Breast Cancer Translational Research Laboratory, Jules Bordet Institute, Université Libre de Bruxelles (ULB), Boulevard de Waterloo, 125-1000 Brussels, Belgium.
authors.forename: Françoise
authors.initials: F
authors.lastname: Rothé
authors.affiliation: IRIBHM, Université Libre de Bruxelles (ULB), Route de Lennik, 808-1070 Brussels, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Lefort
authors.affiliation: IRIBHM, Université Libre de Bruxelles (ULB), Route de Lennik, 808-1070 Brussels, Belgium.
authors.forename: Frederick
authors.initials: F
authors.lastname: Libert
authors.affiliation: Breast Cancer Translational Research Laboratory, Jules Bordet Institute, Université Libre de Bruxelles (ULB), Boulevard de Waterloo, 125-1000 Brussels, Belgium.
authors.forename: David
authors.initials: D
authors.lastname: Brown
authors.affiliation: Breast Cancer Translational Research Laboratory, Jules Bordet Institute, Université Libre de Bruxelles (ULB), Boulevard de Waterloo, 125-1000 Brussels, Belgium.
authors.forename: Naima
authors.initials: N
authors.lastname: Kheddoumi
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
authors.forename: Adam
authors.initials: A
authors.lastname: Shlien
authors.affiliation: IRIBHM, Université Libre de Bruxelles (ULB), Route de Lennik, 808-1070 Brussels, Belgium.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Konopka
authors.affiliation: Breast Cancer Translational Research Laboratory, Jules Bordet Institute, Université Libre de Bruxelles (ULB), Boulevard de Waterloo, 125-1000 Brussels, Belgium.
authors.forename: Roberto
authors.initials: R
authors.lastname: Salgado
authors.affiliation: Department of Pathology, Jules Bordet Institute, Université Libre de Bruxelles (ULB), Boulevard de Waterloo, 125-1000 Brussels, Belgium.
authors.forename: Denis
authors.initials: D
authors.lastname: Larsimont
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Kornelia
authors.initials: K
authors.lastname: Polyak
authors.affiliation: Molecular Immunology Unit, Jules Bordet Institute, Université Libre de Bruxelles (ULB), Boulevard de Waterloo, 125-1000 Brussels, Belgium.
authors.forename: Karen
authors.initials: K
authors.lastname: Willard-Gallo
authors.affiliation: Breast Cancer Translational Research Laboratory, Jules Bordet Institute, Université Libre de Bruxelles (ULB), Boulevard de Waterloo, 125-1000 Brussels, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Desmedt
authors.affiliation: Department of Medicine, Jules Bordet Institute, Université Libre de Bruxelles (ULB), Boulevard de Waterloo, 125-1000 Brussels, Belgium.
authors.forename: Martine
authors.initials: M
authors.lastname: Piccart
authors.affiliation: Department of Genetics, Hôpital Erasme, Route de Lennik, 808-1070 Brussels, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Abramowicz
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Campbell
authors.affiliation: Breast Cancer Translational Research Laboratory, Jules Bordet Institute, Université Libre de Bruxelles (ULB), Boulevard de Waterloo, 125-1000 Brussels, Belgium; Department of Medicine, Jules Bordet Institute, Université Libre de Bruxelles (ULB), Boulevard de Waterloo, 125-1000 Brussels, Belgium. Electronic address: christos.sotiriou@bordet.be.
authors.forename: Christos
authors.initials: C
authors.lastname: Sotiriou
authors.affiliation: IRIBHM, Université Libre de Bruxelles (ULB), Route de Lennik, 808-1070 Brussels, Belgium; WELBIO, Route de Lennik, 808-1070 Brussels, Belgium. Electronic address: vdetours@ulb.ac.be.
authors.forename: Vincent
authors.initials: V
authors.lastname: Detours
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics*; D017209:Apoptosis; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D049109:Cell Proliferation; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism; D061986:MCF-7 Cells; D008969:Molecular Sequence Data; D017393:RNA Editing; D016601:RNA-Binding Proteins / Q000235:genetics*; D059467:Transcriptome
chemical_list: D007370:Interferon Type I; D016601:RNA-Binding Proteins; C000595356:ADAR protein, human; D000243:Adenosine Deaminase