Dissecting the Role of MYCN in Neuroepithelial Stem Cells towards the Pathogenesis of Embryonal Brain Tumours
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Embargo End Date
2025-11-29
ICR Authors
Authors
Shrestha, S
Document Type
Thesis or Dissertation
Date
2025-05-29
Date Accepted
Abstract
This thesis investigates the roles of neuroepithelial stem (NES) cells and the transcription factor MYCN in embryonal brain tumours, specifically embryonal tumour with multilayered rosettes (ETMR) and medulloblastoma (MB). It aims to elucidate how MYCN overexpression in NES cells contributes to the development of these tumours, addressing a gap in our understanding of the connection between early neural development and oncogenesis. NES cells, essential for neural development, differentiate into various neural cell types. The dysregulation of crucial genes that govern the state of NES cells can lead to abnormal development, such as tumorigenesis. This research underscores the importance of NES cells as a potential origin of these tumours and examines the role of MYCN, a gene pivotal for cell cycle regulation and neurogenesis, which is pathologically overexpressed in several paediatric brain tumours. The study emphasises the critical early signalling pathways, such as Sonic hedgehog (Shh) and Wnt, that regulate neural development. MYCN, a downstream target of these pathways, is frequently deregulated in ETMR and MB, implicating it in the pathology of these diseases. Through exploring the interplay between MYCN function, NES cell biology, and tumourigenesis, this thesis provides insights into the molecular mechanisms driving these cancers. Utilising in vitro and in vivo models to replicate the disease processes, this work not only clarifies the oncogenic role of MYCN and NES cells in embryonal brain tumours but also pioneers the identification of the cell of origin for ETMR. This achievement introduces a robust humanised model, addressing a significant gap in the field. It paves the way for further exploration into tumourigenesis and the development of targeted therapies, promising to enhance our understanding and management of these devastating rare childhood brain tumours.
Citation
2025
DOI
Source Title
Publisher
Institute of Cancer Research (University Of London)
ISSN
eISSN
Collections
Research Team
Paediatric Tumour Biology