title: Identification of recurrent regulated alternative splicing events across human solid tumors.
abstract: Cancer is a complex disease that involves aberrant gene expression regulation. Discriminating the modified expression patterns driving tumor biology from the many that have no or little contribution is important for understanding cancer molecular basis. Recurrent deregulation patterns observed in multiple cancer types are enriched for such driver events. Here, we studied splicing alterations in hundreds of matched tumor and normal RNA-seq samples of eight solid cancer types. We found hundreds of cassette exons for which splicing was altered in multiple cancer types and identified a set of highly frequent altered splicing events. Specific splicing regulators, including RBFOX2, MBNL1/2 and QKI, appear to account for many splicing alteration events in multiple cancer types. Together, our results provide a first global analysis of regulated splicing alterations in cancer and identify common events with a potential causative role in solid tumor development.
authors.affiliation: Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.
authors.forename: Miri
authors.initials: M
authors.lastname: Danan-Gotthold
authors.affiliation: Department of Biochemistry and Molecular Biology, the Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Ein Karem, 91120 Jerusalem, Israel.
authors.forename: Regina
authors.initials: R
authors.lastname: Golan-Gerstl
authors.affiliation: Raymond and Beverly Sackler School of Physics and Astronomy and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Eli
authors.initials: E
authors.lastname: Eisenberg
authors.affiliation: Department of Pathology, Hadassah Medical Center, Hebrew University, Jerusalem, Israel.
authors.forename: Keren
authors.initials: K
authors.lastname: Meir
authors.affiliation: Department of Biochemistry and Molecular Biology, the Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Ein Karem, 91120 Jerusalem, Israel erez.levanon@biu.ac.il.
authors.forename: Rotem
authors.initials: R
authors.lastname: Karni
authors.affiliation: Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel erez.levanon@biu.ac.il.
authors.forename: Erez Y
authors.initials: EY
authors.lastname: Levanon
mesh_terms: D017398:Alternative Splicing; D005091:Exons; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D038621:Regulatory Sequences, Ribonucleic Acid; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: C490832:QKI protein, human; C454924:RBFOX2 protein, human; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D038621:Regulatory Sequences, Ribonucleic Acid; D012097:Repressor Proteins