title: Identification of differentially regulated splice variants and novel exons in glial brain tumors using exon expression arrays.
abstract: Aberrant splice variants are involved in the initiation and/or progression of glial brain tumors. We therefore set out to identify splice variants that are differentially expressed between histologic subgroups of gliomas. Splice variants were identified using a novel platform that profiles the expression of virtually all known and predicted exons present in the human genome. Exon-level expression profiling was done on 26 glioblastomas, 22 oligodendrogliomas, and 6 control brain samples. Our results show that Human Exon arrays can identify subgroups of gliomas based on their histologic appearance and genetic aberrations. We next used our expression data to identify differentially expressed splice variants. In two independent approaches, we identified 49 and up to 459 exons that are differentially spliced between glioblastomas and oligodendrogliomas, a subset of which (47% and 33%) were confirmed by reverse transcription-PCR (RT-PCR). In addition, exon level expression profiling also identified >700 novel exons. Expression of approximately 67% of these candidate novel exons was confirmed by RT-PCR. Our results indicate that exon level expression profiling can be used to molecularly classify brain tumor subgroups, can identify differentially regulated splice variants, and can identify novel exons. The splice variants identified by exon level expression profiling may help to detect the genetic changes that cause or maintain gliomas and may serve as novel treatment targets.
authors.affiliation: Department of Neurology, Erasmus MC, Rotterdam, the Netherlands. p.french@erasmusmc.nl
authors.forename: Pim J
authors.initials: PJ
authors.lastname: French
authors.forename: Justine
authors.initials: J
authors.lastname: Peeters
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Horsman
authors.forename: Elza
authors.initials: E
authors.lastname: Duijm
authors.forename: Ivar
authors.initials: I
authors.lastname: Siccama
authors.forename: Martin J
authors.initials: MJ
authors.lastname: van den Bent
authors.forename: Theo M
authors.initials: TM
authors.lastname: Luider
authors.forename: Johan M
authors.initials: JM
authors.lastname: Kros
authors.forename: Peter
authors.initials: P
authors.lastname: van der Spek
authors.forename: Peter A
authors.initials: PA
authors.lastname: Sillevis Smitt
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D005091:Exons; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods*; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017403:In Situ Hybridization; D020033:Protein Isoforms / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020033:Protein Isoforms