Journal article
RNA sequencing of Sleeping Beauty transposon-induced tumors detects transposon-RNA fusions in forward genetic cancer screens
Genome research, Vol.26(1), pp.119-129
01/2016
DOI: 10.1101/gr.188649.114
PMCID: PMC4691744
PMID: 26553456
Abstract
Forward genetic screens using Sleeping Beauty (SB)-mobilized T2/Onc transposons have been used to identify common insertion sites (CISs) associated with tumor formation. Recurrent sites of transposon insertion are commonly identified using ligation-mediated PCR (LM-PCR). Here, we use RNA sequencing (RNA-seq) data to directly identify transcriptional events mediated by T2/Onc. Surprisingly, the majority (∼80%) of LM-PCR identified junction fragments do not lead to observable changes in RNA transcripts. However, in CIS regions, direct transcriptional effects of transposon insertions are observed. We developed an automated method to systematically identify T2/Onc-genome RNA fusion sequences in RNA-seq data. RNA fusion-based CISs were identified corresponding to both DNA-based CISs (Cdkn2a, Mycl1, Nf2, Pten, Sema6d, and Rere) and additional regions strongly associated with cancer that were not observed by LM-PCR (Myc, Akt1, Pth, Csf1r, Fgfr2, Wisp1, Map3k5, and Map4k3). In addition to calculating recurrent CISs, we also present complementary methods to identify potential driver events via determination of strongly supported fusions and fusions with large transcript level changes in the absence of multitumor recurrence. These methods independently identify CIS regions and also point to cancer-associated genes like Braf. We anticipate RNA-seq analyses of tumors from forward genetic screens will become an efficient tool to identify causal events.
Details
- Title: Subtitle
- RNA sequencing of Sleeping Beauty transposon-induced tumors detects transposon-RNA fusions in forward genetic cancer screens
- Creators
- Nuri A Temiz - Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USABranden S Moriarity - Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA; Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455, USA; Brain Tumor Program, University of Minnesota, Minneapolis, Minnesota 55455, USA; Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, USANatalie K Wolf - Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA; Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455, USA; Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, USAJesse D Riordan - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa 52242, USAAdam J Dupuy - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa 52242, USADavid A Largaespada - Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA; Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455, USA; Brain Tumor Program, University of Minnesota, Minneapolis, Minnesota 55455, USA; Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota 55455, USAAaron L Sarver - Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA
- Resource Type
- Journal article
- Publication Details
- Genome research, Vol.26(1), pp.119-129
- Publisher
- United States
- DOI
- 10.1101/gr.188649.114
- PMID
- 26553456
- PMCID
- PMC4691744
- ISSN
- 1088-9051
- eISSN
- 1549-5469
- Grant note
- P30 CA077598 / NCI NIH HHS P30 CA086862 / NCI NIH HHS R01 CA113636 / NCI NIH HHS
- Language
- English
- Date published
- 01/2016
- Academic Unit
- Anatomy and Cell Biology; Pathology
- Record Identifier
- 9984025371802771
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