TY  - JOUR
A1  - Smid, Marcel
A1  - Wilting, Saskia
A1  - Uhr, Katharina
A1  - Rodriguez-Gonzalez, Germán
A1  - de Weerd, Vanja
A1  - Prager-Van der Smissen, Wendy
A1  - van der Vlugt -Daane, Michelle
A1  - van Galen, Anne
A1  - Nik-Zainal, Serena
A1  - Butler, Adam
A1  - Martin, Sancha
A1  - Davies, Helen
A1  - Staaf, Johan
A1  - van de Vijver, Marc
A1  - Richardson, Andrea
A1  - MacGrogan, Gaeten
A1  - Salgado, Roberto
A1  - van den Eynden, Gert
A1  - Purdie, Colin
A1  - Thompson, Alastair
A1  - Caldas, Carlos
A1  - Span, Paul
A1  - Sweep, Fred
A1  - Simpson, Peter
A1  - Lakhani, Sunil
A1  - van Laere, Steven
A1  - Desmedt, Christine
A1  - Paradiso, Angelo
A1  - Eyfjord, Jorunn
A1  - Broeks, Annegien
A1  - Vincent-Solomon, Anne
A1  - Futreal, Andrew
A1  - Knappskog, Stian
A1  - King, Tara
A1  - Viari, Alain
A1  - Børresen-Dale, Anne-Lise
A1  - Stunnenberg, Hendrik
A1  - Stratton, Mike
A1  - Foekens, John
A1  - Sieuwerts, Anieta
A1  - Martens, John
T1  - The circular RNome of primary breast cancer
Y1  - 2019/01/28 
JF  - Genome Research 
JO  - Genome Research 
DO  - 10.1101/gr.238121.118 
SP  - gr.238121.118 
UR  - http://genome.cshlp.org/content/early/2019/01/28/gr.238121.118.abstract 
N2  - Circular RNAs (circRNAs) are a class of RNA 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 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. 
ER  -