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| Status |
Public on Apr 24, 2024 |
| Title |
Screen for genes showing synthetic lethality with NF2 in Schwannoma [RNA-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Neurofibromatosis Type II is a genetic condition caused by loss of the NF2 gene, resulting in activation of the YAP/TAZ pathway and recurrent growth of benign tumors from Schwann cells, the glia of the peripheral nervous system. Unfortunately, no pharmacological therapy is currently available for NFII. Here, we undertake a genome-wide CRISPR/cas9 screen to search for synthetic-lethal genes that, when inhibited, cause death of NF2 mutant cells but not NF2 wildtype cells. We thereby identify ACSL3 and G6PD as two synthetic-lethal partners for NF2. We find that NF2 mutant Schwann cells are vulnerable to G6PD inhibition because they have low levels of ME1. G6PD and ME1 redundantly generate cytosolic NADPH needed by cells to fight oxidative stress. Lack of either one of the two is compatible with cell viability, but down-regulation of both leads to Schwann cell death. Since genetic deficiency for G6PD is tolerated in the human population, this raises the possibility that G6PD could be a pharmacological target for NFII.
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| Overall design |
RNA-Seq Schwann Cells, NF2-WT, Schwann Cells, NF2-KO, Schwann Cells, NF2-WT + Cas9, Schwann Cells, NF2-KO + Cas9
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| Contributor(s) |
Athena K, Aurelio T |
| Citation missing |
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| Submission date |
Dec 01, 2022 |
| Last update date |
Apr 24, 2024 |
| Contact name |
Aurelio A Teleman |
| Organization name |
German Cancer Research Center (DKFZ)
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| Street address |
Im Neuenheimer Feld 580
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| City |
Heidelberg |
| ZIP/Postal code |
69120 |
| Country |
Germany |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE219141 |
Screen for genes showing synthetic lethality with NF2 in Schwannoma |
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| Relations |
| BioProject |
PRJNA907235 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE219135_NF2_RNA-seq.txt.gz |
482.3 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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