- Author
-
A. Bongaarts
- Title
- Molecular features of low-grade developmental brain tumours
- Subtitle
- Focusing on subependymal giant cell astrocytomas in tuberous sclerosis complex
- Supervisors
- Co-supervisors
-
A. Mühlebner-Fahrngruber
A.Y.N. Schouten-van Meeteren - Award date
- 30 April 2021
- Number of pages
- 223
- ISBN
- 9789463327527
- Document type
- PhD thesis
- Faculty
- Faculty of Medicine (AMC-UvA)
- Abstract
-
Although it is not unusual for brain tumours to clinically manifest with seizures, slowly growing low grade tumours tend to be especially epileptogenic. Low-grade epilepsy-associated tumours, including glioneuronal tumours (GNTs), are characterized by a history of 2 or more years of drug-resistant chronic epilepsy and often arise in younger age groups. Paediatric low grade gliomas (pLGGs) account for ~30% of brain tumours in children and can have a hereditary component. Subependymal giant cell astrocytomas (SEGAs) are low grade brain tumours that occur almost exclusively in patients with tuberous sclerosis complex (TSC), a monogenic disease caused by a mutations in either the TSC1 or TSC2 gene, resulting in constitutive activation of the mechanistic target of rapamycin complex (mTOR) pathway. SEGAs are not the direct cause of epilepsy in patients with TSC, but can effect seizure burden. The aim was to investigate the molecular mechanisms involved in SEGA development and growth on a (epi)genomic, transcriptomic and proteomic level and to investigate molecular features of several GNTs. Overall, this thesis provided novel insights into the molecular pathways involved in SEGA pathology, including the MAPK pathway and the extracellular matrix organization. Overexpression of LAMTOR1-5 in SEGAs provides a new link between the MAPK and mTOR pathway in SEGAs and could therefore also play an interesting role in other tumours where both pathways are effected. Furthermore, we show how miRNAs can be used to distinguish between tumour entities and how they can target important pathways in both SEGAs and GNTs.
- Persistent Identifier
- https://hdl.handle.net/11245.1/92f389f2-4d14-4cca-a9a8-467e911176e2
- Downloads
-
Thesis (complete)
Front matter
Chapter 1: General introduction & outline of the thesis
Chapter 2: Subependymal giant cell astrocytomas in tuberous sclerosis complex have consistent TSC1/TSC2 biallelic inactivation, and no BRAF mutations
Chapter 3: Distinct DNA methylation patterns of subependymal giant cell astrocytomas in tuberous sclerosis complex
Chapter 4: The coding and non-coding transcriptional landscape of subependymal giant cell astrocytomas
Chapter 5: Dysregulation of the MMP/TIMP proteolytic system in subependymal giant cell astrocytomas in patients with tuberous sclerosis complex: Modulation of MMP by microRNA-320d in vitro
Chapter 6: MicroRNA519d and microRNA4758 can identify gangliogliomas from dysembryoplastic neuroepithelial tumours and astrocytomas
Chapter 7: General discussion
Summary; Nederlandse samenvatting; List of publications; Portfolio; Curriculum vitae; Acknowledgements
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