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  • Smid, MarcelErasmus University Medical Center (author)

The circular RNome of primary breast cancer

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • 2019-01-28
  • Cold Spring Harbor Laboratory,2019
  • 11 s.

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:4e293ab2-6cbb-44a8-ba36-2e6258491a84
  • https://lup.lub.lu.se/record/4e293ab2-6cbb-44a8-ba36-2e6258491a84URI
  • https://doi.org/10.1101/gr.238121.118DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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.

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Wilting, Saskia M.Erasmus University Medical Center (author)
  • Uhr, KatharinaErasmus University Medical Center (author)
  • Rodríguez-González, F. GermánErasmus University Medical Center (author)
  • De Weerd, VanjaErasmus University Medical Center (author)
  • Prager-Van Der Smissen, Wendy J.C.Erasmus University Medical Center (author)
  • Van Der Vlugt-Daane, MichelleErasmus University Medical Center (author)
  • Van Galen, AnneErasmus University Medical Center (author)
  • Nik-Zainal, SerenaCambridge University Hospitals NHS Foundation Trust,Wellcome Trust Sanger Institute (author)
  • Butler, AdamWellcome Trust Sanger Institute (author)
  • Martin, SanchaWellcome Trust Sanger Institute (author)
  • Davies, Helen R.Wellcome Trust Sanger Institute (author)
  • Staaf, JohanLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Research Group Lung Cancer,Lund University Research Groups(Swepub:lu)onk-jst (author)
  • Van De Vijver, Marc J.Academic Medical Center of University of Amsterdam (AMC) (author)
  • Richardson, Andrea L.Brigham and Women's Hospital / Harvard Medical School,Dana-Farber Cancer Institute (author)
  • MacGrogan, GaëtenInstitut Bergoníe (author)
  • Salgado, RobertoUniversity of Antwerp,Institut Jules Bordet (author)
  • Van Den Eynden, Gert G.G.M.University of Antwerp,Institut Jules Bordet (author)
  • Purdie, Colin A.Ninewells Hospital and Medical School (author)
  • Thompson, Alastair M.Ninewells Hospital and Medical School (author)
  • Caldas, CarlosUniversity of Cambridge (author)
  • Span, Paul N.Radboud University Nijmegen (author)
  • Sweep, Fred C.G.J.Radboud University Nijmegen (author)
  • Simpson, Peter T.University of Queensland (author)
  • Lakhani, Sunil R.Royal Brisbane and Women's Hospital,University of Queensland (author)
  • Van Laere, StevenUniversity of Antwerp (author)
  • Desmedt, ChristineInstitut Jules Bordet (author)
  • Paradiso, AngeloIstituto Tumori 'Giovanni Paolo II' (author)
  • Eyfjord, JorunnUniversity of Iceland (author)
  • Broeks, AnnegienNetherlands Cancer Institute (author)
  • Vincent-Salomon, AnneCurie Institute, Paris (author)
  • Futreal, Andrew P.University of Texas (author)
  • Knappskog, StianHaukeland University Hospital,University of Bergen (author)
  • King, TariMemorial Sloan-Kettering Cancer Center (author)
  • Viari, AlainNational Institute for Research in Computer Science and Control (INIRA),Centre Léon Bérard (author)
  • Børresen-Dale, Anne LiseOslo university hospital,University of Oslo (author)
  • Stunnenberg, Hendrik G.Radboud University Nijmegen (author)
  • Stratton, MikeWellcome Trust Sanger Institute (author)
  • Foekens, John A.Erasmus University Medical Center (author)
  • Sieuwerts, Anieta M.Erasmus University Medical Center (author)
  • Martens, John W.M.Erasmus University Medical Center (author)
  • Erasmus University Medical CenterCambridge University Hospitals NHS Foundation Trust (creator_code:org_t)

Related titles

  • In:Genome Research: Cold Spring Harbor Laboratory29:3, s. 356-3661088-90511549-5469

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