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Identification of novel fusion genes in lung cancer using breakpoint assembly of transcriptome sequencing data

Fernandez-Cuesta, Lynnette; Sun, Ruping; Menon, Roopika; George, Julie; Lorenz, Susanne; Meza-Zepeda, Leonardo; Peifer, Martin; Plenker, Dennis; Heuckmann, Johannes; Leenders, Frauke; Zander, Thomas; Dahmen, Ilona; Koker, Mirjam; Schöttle, Jakob; Ullrich, Roland; Altmüller, Janine; Becker, Christian; Nürnberg, Peter; Seidel, Henrik; Böhm, Diana; Göke, Friederike; Ansén, Sascha; Russell, Prudence; Wright, Gavin; Wainer, Zoe; Solomon, Benjamin; Petersen, Iver; Clement, Joachim; Sänger, Jörg; Brustugun, Odd-Terje; Helland, Åslaug; Solberg, Steinar; Lund-Iversen, Marius; Buettner, Reinhard; Wolf, Jürgen; Brambilla, Elisabeth; Vingron, Martin; Perner, Sven; Haas, Stefan; Thomas, Roman

Genomic translocation events frequently underlie cancer development through generation of gene fusions with oncogenic properties. Identification of such fusion transcripts by transcriptome sequencing might help to discover new potential therapeutic targets. We developed TRUP (Tumor-specimen suited RNA-seq Unified Pipeline) (https://github.com/ruping/TRUP), a computational approach that combines split-read and read-pair analysis with de novo assembly for the identification of chimeric transcripts in cancer specimens. We apply TRUP to RNA-seq data of different tumor types, and find it to be more sensitive than alternative tools in detecting chimeric transcripts, such as secondary rearrangements in EML4-ALK-positive lung tumors, or recurrent inactivating rearrangements affecting RASSF8.

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Academic Units
Systems Biology
Publisher
BioMed Central
Published Here
January 21, 2015