TY - JOUR T1 - Principles governing A-to-I RNA editing in the breast cancer transcriptome JF - bioRxiv DO - 10.1101/012849 SP - 012849 AU - Debora Fumagalli AU - David Gacquer AU - Françoise Rothé AU - Anne Lefort AU - Frederick Libert AU - David Brown AU - Naima Kheddoumi AU - Adam Shlien AU - Tomasz Konopka AU - Roberto Salgado AU - Denis Larsimont AU - Kornelia Polyak AU - karen Willard-Gallo AU - Christine Desmedt AU - Martine Piccart AU - Marc Abramowicz AU - Peter J Campbell AU - Christos Sotiriou AU - Vincent Detours Y1 - 2014/01/01 UR - http://biorxiv.org/content/early/2014/12/16/012849.abstract N2 - A-to-I editing substitutes inosines for adenosines at specific positions in mRNAs and can substantially alter a cell’s transcriptome. Currently, little is known about how this type of editing functions in cancer. This study demonstrates that A-to-I edited mRNA loci are conserved not only across matched normal and tumor breast tissues but also between patients; however, the editing frequency is higher in tumor compared to normal breast tissue. We developed a model that shows the editing enzyme ADAR uniformly controls the editing frequency across all loci, proportional to each individual locus’ editability, which is a property of its surrounding nucleotide sequence. We also demonstrate that the type I interferon response and ADAR DNA copy number together determine ADAR expression in breast and potentially the vast majority of human cancers. ADAR silencing using shRNA lentivirus transduction in breast cancer cell lines led to a decrease in cell proliferation and an increase in apoptosis. Our results reveal that A-to-I editing is a pervasive but well controlled phenomenon in cancer that can profoundly influence the transcriptome and cellular functions in breast cancer. ER -