The circular RNome of primary breast cancer
| Autor: | Steven Van Laere, Colin A. Purdie, John A. Foekens, Gaëten MacGrogan, Marcel Smid, Andrew Futreal, Vanja de Weerd, Paul N. Span, Marc J. van de Vijver, Jorunn E. Eyfjord, Serena Nik-Zainal, F. Germán Rodríguez-González, Roberto Salgado, Peter T. Simpson, Christine Desmedt, Wendy J. C. Prager-van der Smissen, Fred C.G.J. Sweep, Tari A. King, Adam Butler, Michael R. Stratton, Carlos Caldas, Gert Van den Eynden, Sunil R. Lakhani, Saskia M. Wilting, Alastair M. Thompson, Angelo Paradiso, John W.M. Martens, Anne Vincent-Salomon, Johan Staaf, Anne van Galen, Sancha Martin, Hendrik G. Stunnenberg, Annegien Broeks, Andrea L. Richardson, Anne Lise Børresen-Dale, Helen Davies, Michelle van der Vlugt-Daane, Katharina Uhr, Stian Knappskog, Alain Viari, Anieta M. Sieuwerts |
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| Přispěvatelé: | Medical Oncology, Smid, Marcel [0000-0003-0605-1901], Apollo - University of Cambridge Repository, Pathology, CCA - Cancer biology and immunology, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Cambridge University Hospitals - NHS (CUH), University of Cambridge [UK] (CAM), The Wellcome Trust Sanger Institute [Cambridge], Lund University [Lund], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Dana-Farber Cancer Institute [Boston], Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Institut Bergonié [Bordeaux], UNICANCER, Breast Cancer Translational Research Laboratory, Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Translational Cancer Research Unit [Antwerp], Department of Pathology [Dundee], Ninewells Hospital and Medical School [Dundee], Radboud University Medical Center [Nijmegen], University of Southern Queensland (USQ), University of Antwerp (UA), Istituto Tumori 'Giovanni Paolo II' [Bari], University of Iceland [Reykjavik], Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Génétique et Biologie du Développement, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), The University of Texas M.D. Anderson Cancer Center [Houston], University of Bergen (UiB), Haukeland University Hospital, Memorial Sloane Kettering Cancer Center [New York], Synergie Lyon Cancer [Lyon], Centre Léon Bérard [Lyon], Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Institute for Cancer Research [Oslo], Oslo University Hospital [Oslo], Fondation Synergie Lyon Cancer [Lyon], Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Génétique clinique
Proliferation index [SDV]Life Sciences [q-bio] Transcriptome Exon Breast cancer 0302 clinical medicine Brjóstakrabbamein MUTATIONAL PROCESSES Genetics (clinical) Genetics & Heredity 0303 health sciences Gene knockdown Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17] ABUNDANT CREB-Binding Protein Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] 3. Good health GENOME Chemistry Lymphatic Metastasis RNA splicing MCF-7 Cells Female Engineering sciences. Technology Biologie Life Sciences & Biomedicine Biochemistry & Molecular Biology Breast Neoplasms Biology 03 medical and health sciences All institutes and research themes of the Radboud University Medical Center SDG 3 - Good Health and Well-being REVEALS Biomarkers Tumor Genetics medicine Erfðafræði Humans TAMOXIFEN Molecular Biology Gene SIGNATURES 030304 developmental biology Science & Technology LANDSCAPE Research MICRORNA Cancer RNA Circular medicine.disease DNA-rannsóknir GENE RNAs Repressor Proteins Biotechnology & Applied Microbiology Cancer research RNA Human medicine Carrier Proteins 030217 neurology & neurosurgery |
| Zdroj: | Genome Research Genome Research, 29(3), 356-366. Cold Spring Harbor Laboratory Press Genome research, 29(3), 356-366. Cold Spring Harbor Laboratory Press Genome Research, Cold Spring Harbor Laboratory Press, 2019, 29 (3), pp.356-366. ⟨10.1101/gr.238121.118⟩ Genome Research, 29, 356-366 Genome research, 29 (3 Genome research Genome Research, 29, 3, pp. 356-366 Genome Research, 2019, 29 (3), pp.356-366. ⟨10.1101/gr.238121.118⟩ |
| ISSN: | 1088-9051 1549-5469 |
| DOI: | 10.1101/gr.238121.118⟩ |
| Popis: | Publisher's version (útgefin grein) Circular RNAs (circRNAs) are a class of RNAs that is under increasing scrutiny, although their functional roles are debated. We analyzed RNA-seq data of 348 primary breast cancers and developed a method to identify circRNAs that does not rely on unmapped reads or known splice junctions. We identified 95,843 circRNAs, of which 20,441 were found recurrently. Of the circRNAs that match exon boundaries of the same gene, 668 showed a poor or even negative (R < 0.2) correlation with the expression level of the linear gene. In silico analysis showed only a minority (8.5%) of circRNAs could be explained by known splicing events. Both these observations suggest that specific regulatory processes for circRNAs exist. We confirmed the presence of circRNAs of CNOT2, CREBBP, and RERE in an independent pool of primary breast cancers. We identified circRNA profiles associated with subgroups of breast cancers and with biological and clinical features, such as amount of tumor lymphocytic infiltrate and proliferation index. siRNA-mediated knockdown of circCNOT2 was shown to significantly reduce viability of the breast cancer cell lines MCF-7 and BT-474, further underlining the biological relevance of circRNAs. Furthermore, we found that circular, and not linear, CNOT2 levels are predictive for progression-free survival time to aromatase inhibitor (AI) therapy in advanced breast cancer patients, and found that circCNOT2 is detectable in cell-free RNA from plasma. We showed that circRNAs are abundantly present, show characteristics of being specifically regulated, are associated with clinical and biological properties, and thus are relevant in breast cancer. We thank the Erasmus MC Cancer Computational Biology Center for giving access to their IT infrastructure and the software that was used for the computations and data analysis in this study. We thank Sandra Albassam for her help with the first versions of the script to identify circular regions. We thank Maurice P.H.M. Jansen, Jean C. Helmijr, Inge de Kruijff, and Manouk K. Bos for their help in evaluating plasma samples that were gathered in the EU-FP7 CareMore (nr 601760) project. We thank for technical support Miriam Ragle Aure and Anita Langerød of the Oslo University Hospital, Norway; Ewan Birney of the European Bioinformatics Institute, UK; and Stefania Tommasi of the IRCCS Istituto Tumori “Giovanni Paolo II,” Bari, Italy. We thank the Oslo Breast Cancer Research Consortium (OSBREAC), Norway (https://www.ous-research.no/home/kgjebsen/home/14105) for contributing patient samples and Sabine Linn and Marleen Kok of The Netherlands Cancer Institute for contributing samples for the AI cohort. Finally, we thank all members of the ICGC Breast Cancer Working Group. This work has been funded through the ICGC Breast Cancer Working group by the Breast Cancer Somatic Genetics Study (a European research project funded by the European Community’s Seventh Framework Programme (FP7/2010-2014) under the grant agreement number 242006) and the Triple Negative project funded by the Wellcome Trust (grant reference 077012/Z/05/Z). F.G.R.-G. and S.M. were funded by BASIS. J.A.F. was funded through an ERC Advanced Grant (ERC-2012-AdG-322737) and ERC Proof-of-Concept Grant (ERC-2017-PoC-767854). K.U. was funded by the Daniel den Hoed Foundation. S.N.-Z. is a Wellcome Beit Fellow and personally funded by a Wellcome Trust Intermediate Fellowship (WT100183MA). A.L.R. is partially supported by the Dana-Farber/Harvard Cancer Center SPORE in Breast Cancer (NIH/NCI 5 P50 CA16 8504-02). A.M.S. was supported by Cancer Genomics Netherlands (CGC.nl) through a grant from the Netherlands Organization of Scientific research (NWO). M. Smid was supported by the EU-FP7-DDR response project. C.D. was supported by a grant from the Breast Cancer Research Foundation. J.E. was funded by The Icelandic Centre for Research (RANNIS). |
| Databáze: | OpenAIRE |
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