Global analysis of aberrant pre-mRNA splicing in glioblastoma using exon expression arraysReportar como inadecuado




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BMC Genomics

, 9:216

First Online: 12 May 2008Received: 19 October 2007Accepted: 12 May 2008

Abstract

BackgroundTumor-predominant splice isoforms were identified during comparative in silico sequence analysis of EST clones, suggesting that global aberrant alternative pre-mRNA splicing may be an epigenetic phenomenon in cancer. We used an exon expression array to perform an objective, genome-wide survey of glioma-specific splicing in 24 GBM and 12 nontumor brain samples. Validation studies were performed using RT-PCR on glioma cell lines, patient tumor and nontumor brain samples.

ResultsIn total, we confirmed 14 genes with glioma-specific splicing; seven were novel events identified by the exon expression array A2BP1, BCAS1, CACNA1G, CLTA, KCNC2, SNCB, and TPD52L2. Our data indicate that large changes > 5-fold in alternative splicing are infrequent in gliomagenesis < 3% of interrogated RefSeq entries. The lack of splicing changes may derive from the small number of splicing factors observed to be aberrantly expressed.

ConclusionWhile we observed some tumor-specific alternative splicing, the number of genes showing exclusive tumor-specific isoforms was on the order of tens, rather than the hundreds suggested previously by in silico mining. Given the important role of alternative splicing in neural differentiation, there may be selective pressure to maintain a majority of splicing events in order to retain glial-like characteristics of the tumor cells.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2164-9-216 contains supplementary material, which is available to authorized users.

Keith A Baggerly, Gilbert J Cote and Ralf Krahe contributed equally to this work.

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Autor: Hannah C Cheung - Keith A Baggerly - Spiridon Tsavachidis - Linda L Bachinski - Valerie L Neubauer - Tamara J Nixon - K

Fuente: https://link.springer.com/article/10.1186/1471-2164-9-216







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