Ferreira, Andreia Liliana;
(2025)
The role of isocitrate dehydrogenase mutations in experimental tumourigenesis of the central nervous system.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Aims: This study investigates the impact of mutant isocitrate dehydrogenase (IDH) 1 or 2 on tumourigenesis, tumour phenotype, growth dynamics, survival, and latency in a glioma mouse model. / Methods: Using a mouse model, we employed several experimental approaches: (1) Adenovirus expressing Cre recombinase in the subventricular zone (SVZ) of mice with conditional alleles for p53, Pten and Rb (2) IC transplantation of recombined cells, and (3) administration of tamoxifen-derived metabolites targeting type B cells of the CNS SVZ. Tumours were generated by inactivating p53, Pten and Rb in forebrain progenitors and compared with tumours expressing the IDH1 R132H mutation. / Results: The IDH1 R132H mutation alone did not induce tumours in CNS stem and progenitor cells. Additionally, when combined with p53, Pten and Rb loss, it did not significantly affect tumour phenotype, growth dynamics, survival, or latency. / Conclusion: Further studies are needed to understand the role of mutant IDH1 (R132H) in tumourigenesis, potentially by introducing mutations such as ATRX and CDKN2A/B inactivation, which have been identified in human astrocytomas.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | The role of isocitrate dehydrogenase mutations in experimental tumourigenesis of the central nervous system |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2025. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10209065 |
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