[HTML][HTML] Global analysis of aberrant pre-mRNA splicing in glioblastoma using exon expression arrays
HC Cheung, KA Baggerly, S Tsavachidis, LL Bachinski… - BMC genomics, 2008 - Springer
HC Cheung, KA Baggerly, S Tsavachidis, LL Bachinski, VL Neubauer, TJ Nixon, KD Aldape…
BMC genomics, 2008•SpringerBackground 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 …
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 …
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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