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Title:
Global analysis of aberrant pre-mRNA splicing in glioblastoma using exon expression arrays | BMC Genomics
Description:
Background Tumor-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. Results In 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. Conclusion While 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.
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Keywords {π}
splicing, exon, genes, min, expression, pubmed, article, alternative, samples, google, scholar, additional, figure, file, rna, refseq, cas, gene, array, cancer, entries, data, gbm, events, analysis, psr, brain, rtpcr, values, cell, affymetrix, pvalues, nontumor, differential, total, hybridization, cdna, incubated, aberrant, identified, gliomaspecific, performed, significant, sample, buffer, splice, tumor, factors, reactions, change,
Topics {βοΈ}
semi-quantitative rt-pcr technology access/early access aberrant pre-mrna splicing open access article alternative pre-mrna splicing neuronal-specific splicing regulator glioma-predominant splice isoforms glioma-specific splicing events glioma-specific splicing event cancer-predominant splicing patterns splice regulatory cis-elements generate gbm-specific bands gbm-specific splicing events article download pdf confirmed glioma-specific splicing tissue-specific alternative splicing gbm-specific isoforms varied detectable gbm-specific splicing showed glioma-specific splicing cancer-specific alternative splicing fgfr1 glioma-specific splicing tumor-specific alternative splicing fgfr1-specific splicing switch significant glioma-specific splicing tumour-specific expressed sequences rt-pcr validations shown full size image rt-pcr analysis failed silico genome-wide assessments splicing factor sf2/asf genome-wide ests alignment central nervous system single-stranded target preparation pre-mrna splicing pre-mrna processing rt-pcr-tested genes identify cassette exon rt-pcr validation suggest gene-level rma quantifications large-scale aberrant splicing single cancer-enhancing isoform rt-pcr validations multidrug-resistant phenotype psr specific t-tests global aberrant splicing 14 gbm-specific events aberrant alternative splicing glioma-specific splicing intronic splicing silencer rt-pcr data suggested
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headline:Global analysis of aberrant pre-mRNA splicing in glioblastoma using exon expression arrays
description:Tumor-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. In 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. While 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.
datePublished:2008-05-12T00:00:00Z
dateModified:2008-05-12T00:00:00Z
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keywords:
Alternative Splice
Splice Event
Exon Array
Cassette Exon
Exon Inclusion
Life Sciences
general
Microarrays
Proteomics
Animal Genetics and Genomics
Microbial Genetics and Genomics
Plant Genetics and Genomics
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headline:Global analysis of aberrant pre-mRNA splicing in glioblastoma using exon expression arrays
description:Tumor-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. In 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. While 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.
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Alternative Splice
Splice Event
Exon Array
Cassette Exon
Exon Inclusion
Life Sciences
general
Microarrays
Proteomics
Animal Genetics and Genomics
Microbial Genetics and Genomics
Plant Genetics and Genomics
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