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| Status |
Public on Oct 27, 2020 |
| Title |
The effects of H3.3K27M mutation on developing mouse brain and cooperation with Trp53 on enhancing tumorigenesis in the genetic model of H3.3K27M [RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Diffuse intrinsic pontine gliomas (DIPG) are devastating pediatric brain tumors for which there is no effective therapy. A lack of pre-clinical genetic models has affected efforts to develop therapies targeted to DIPG. Over 60% of DIPG patients carry a mutation in the histone H3F3A gene (H3.3K27M) that is often accompanied by a mutation in the TP53 gene. Here we created a genetic model in which H3.3K27M is expressed under the mouse Fabp7 promoter. These mice have disrupted embryonic development and increased susceptibility to development of lymphomas. Crosses to Trp53 knockout mice further accelerated lymphomagenesis and led to brain tumour development. Some but not all tumours acquired additional oncogenic alterations. The brain tumours faithfully recapitulate the expression profiles of DIPG patients, and brain tumours and lymphomas share significant similarities in pathway alterations, pointing to a core H3.3K27M transcriptome. Overall, this mouse model provides key insights into how H3.3K27M mutations regulate DIPG at the cellular and tumour level.
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| Overall design |
H3.3K27M mice were generated by microinjection. We performed genome-wide RNA-Seq on mid/hind-brains isolated from WT (n=3) and H3.3K27M (n=3) E14.5 embryos, on brains of adult H3.3K27M mice (n=3) and tumours isolated from H3.3K27M mice (brain tumours, n=2; lymphomas, n=3) for a total of 14 samples.
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| Contributor(s) |
Hawkins C, Siddaway R, Pajovic S |
| Citation(s) |
33277484, 35102191 |
| Submission date |
Oct 05, 2018 |
| Last update date |
Feb 18, 2022 |
| Contact name |
Cynthia Hawkins |
| Organization name |
Hospital for Sick Children
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| Street address |
686 Bay Street
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| City |
Toronto |
| State/province |
Ontario |
| ZIP/Postal code |
M6G 0A4 |
| Country |
Canada |
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| Platforms (2) |
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| Samples (14)
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| This SubSeries is part of SuperSeries: |
| GSE120884 |
The effects of H3.3K27M mutation on developing mouse brain and cooperation with Trp53 on enhancing tumorigenesis in the genetic model of H3.3K27M |
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| Relations |
| BioProject |
PRJNA494821 |
| SRA |
SRP163633 |
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