TY - JOUR
T1 - Global analysis of aberrant pre-mRNA splicing in glioblastoma using exon expression arrays
AU - Cheung, Hannah C.
AU - Baggerly, Keith A.
AU - Tsavachidis, Spiridon
AU - Bachinski, Linda L.
AU - Neubauer, Valerie L.
AU - Nixon, Tamara J.
AU - Aldape, Kenneth D.
AU - Cote, Gilbert J.
AU - Krahe, Ralf
N1 - Funding Information:
HCC was supported by the Rosalie B. Hite Fellowship. This study was supported in part by NIH R01 CA67946 and The John K. Funk Endowment (GJC) and the Kleberg Foundation (RK). We are grateful to T. Hai for technical support. This study was part of the Affymetrix (Santa Clara, CA) Technology Access/Early Access (TA/EA) program for the Human Exon Array 1.0 ST.
PY - 2008/5/12
Y1 - 2008/5/12
N2 - 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.
AB - 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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U2 - 10.1186/1471-2164-9-216
DO - 10.1186/1471-2164-9-216
M3 - Article
C2 - 18474104
AN - SCOPUS:44649126097
SN - 1471-2164
VL - 9
JO - BMC genomics
JF - BMC genomics
M1 - 216
ER -