title: Novel fusion genes and chimeric transcripts in ependymal tumors.
abstract: We have previously identified two ALK rearrangements in a subset of ependymal tumors using a combination of cytogenetic data and RNA sequencing. The aim of this study was to perform an unbiased search for fusion transcripts in our entire series of ependymal tumors. Fusion analysis was performed using the FusionCatcher algorithm on 12 RNA-sequenced ependymal tumors. Candidate transcripts were prioritized based on the software's filtering and manual visualization using the BLAST (Basic Local Alignment Search Tool) and BLAT (BLAST-like alignment tool) tools. Genomic and reverse transcriptase PCR with subsequent Sanger sequencing was used to validate the potential fusions. Fluorescent in situ hybridization (FISH) using locus-specific probes was also performed. A total of 841 candidate chimeric transcripts were identified in the 12 tumors, with an average of 49 unique candidate fusions per tumor. After algorithmic and manual filtering, the final list consisted of 24 potential fusion events. Raw RNA-seq read sequences and PCR validation supports two novel fusion genes: a reciprocal fusion gene involving UQCR10 and C1orf194 in an adult spinal ependymoma and a TSPAN4-CD151 fusion gene in a pediatric infratentorial anaplastic ependymoma. Our previously reported ALK rearrangements and the RELA and YAP1 fusions found in supratentorial ependymomas were until now the only known fusion genes present in ependymal tumors. The chimeric transcripts presented here are the first to be reported in infratentorial or spinal ependymomas. Further studies are required to characterize the genomic rearrangements causing these fusion genes, as well as the frequency and functional importance of the fusions. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, Oslo University Hospital, Norway. thaleko@gmail.com.|Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Norway. thaleko@gmail.com.|Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway. thaleko@gmail.com.
authors.forename: Thale Kristin
authors.initials: TK
authors.lastname: Olsen
authors.affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, Oslo University Hospital, Norway.|Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Norway.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Panagopoulos
authors.affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, Oslo University Hospital, Norway.|Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Norway.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Gorunova
authors.affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, Oslo University Hospital, Norway.|Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Norway.
authors.forename: Francesca
authors.initials: F
authors.lastname: Micci
authors.affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, Oslo University Hospital, Norway.
authors.forename: Kristin
authors.initials: K
authors.lastname: Andersen
authors.affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, Oslo University Hospital, Norway.
authors.forename: Hege
authors.initials: H
authors.lastname: Kilen Andersen
authors.affiliation: Department of Neurosurgery, Oslo University Hospital, Norway.
authors.forename: Torstein R
authors.initials: TR
authors.lastname: Meling
authors.affiliation: Department of Neurosurgery, Oslo University Hospital, Norway.
authors.forename: Bernt
authors.initials: B
authors.lastname: Due-Tønnessen
authors.affiliation: Department of Pathology, Rigshospitalet, Copenhagen, Denmark.|Department of Pathology, Oslo University Hospital, Norway.
authors.forename: David
authors.initials: D
authors.lastname: Scheie
authors.affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, Oslo University Hospital, Norway.|Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Norway.|Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway.
authors.forename: Sverre
authors.initials: S
authors.lastname: Heim
authors.affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, Oslo University Hospital, Norway.|Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Norway.|Department of Oncology, Oslo University Hospital-The Norwegian Radium Hospital, Norway.
authors.forename: Petter
authors.initials: P
authors.lastname: Brandal
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D004806:Ependymoma / Q000145:classification / Q000235:genetics* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011379:Prognosis; D012984:Software; D015996:Survival Rate; D060185:Tetraspanin 24 / Q000235:genetics; D059470:Tetraspanins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C554715:CD151 protein, human; D015514:Oncogene Proteins, Fusion; C109139:TSPAN4 protein, human; D060185:Tetraspanin 24; D059470:Tetraspanins