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| Status |
Public on Sep 01, 2016 |
| Title |
Splicing in gliomas |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The objective of our study was to determine whether aberrant alternative splicing could play a role in the malignant phenotype of GBM. Patients with GBM were operated with 5-aminolevulinic fluorescence guided surgery. The fluorescent was used to take biopsies from the tumor center, and from adjacent normal-looking tissue. Three paired normal/GBM samples were analyzed in a HJAY J array. We validated our results with conventional PCR and qRT-PCR in those tumor samples and in ten additional GBMs. We performed functional studies using MTT assays (proliferation) and IF qRT-PCR (differentiation). We generated a list of seven genes with differential alternative splicing between central tumor samples and the adjacent normal-looking tissue. DPF-2(BAF45d) was one of our top candidates. Interestingly, DPF-2 is known as a tumor suppressor gene in the context of the SWI/SNF complex and plays a key role in the development of the central nervous system. The inhibition of our DPF-2 isoform resulted in a significative reduction in proliferation and in a morphology changes towards a more differentiated phenotype in GBM cell lines. Interestingly, our DPF2 tumoral isoform was the predominant transcript in early postnatal murine neural precursors and its expression disappeared as these cells were instructed towards neurons. Our results suggest that the alternative splicing of DPF-2 in GBM could participate in the maintenance of an undifferentiated cellular state. In addition, our data suggest that alternative splicing is a mechanism that could be central to GBM development
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| Overall design |
We compared three paired samples of tumor (glioma)/normal like and 1 sample of pooled brain RNA from healthy donors
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| Contributor(s) |
Aldave G, Gonzalez-Huarriz M, Rubio A, Romero JP, Ravi D, Valcárcel J, Miñana B, Cuadrado-Tejedor M, García-Osta A, Verhaak R, Xipell E, Martínez-Vélez N, Acanda de la Rocha A, Marigil M, Gállego J, Marín-Béjar O, Carro MS, Ferrarese R, Belda C, Ayudos A, Pastor F, Díez-Valle R, Tejada S, Alonso MM |
| Citation(s) |
29373718 |
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| Submission date |
Dec 16, 2015 |
| Last update date |
Oct 15, 2018 |
| Contact name |
Juan Pablo Romero |
| E-mail(s) |
juanpablo.romerorioj@10xgenomics.com
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| Organization name |
10x Genomics
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| Department |
Computational Biology
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| Street address |
6230 Stoneridge Mall Rd
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| City |
Pleasanton |
| State/province |
CA |
| ZIP/Postal code |
94588 |
| Country |
USA |
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| Platforms (1) |
| GPL21251 |
[hjay.1sq ] Affymetrix GeneChip Human HJAY Array |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA306150 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE76070_RAW.tar |
370.3 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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