Hereditary predisposition in pediatric brain cancer

• Applicant: Lena Kutscher, Ph.D.
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Developmental Neurobiology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 497317859

Pediatric cancer is the leading cause of disease-related death in children, and solid tumors of the central nervous system account for approximately 20% of all pediatric cancer. In SHH-medulloblastoma, a childhood tumor arising from the developing cerebellum, hereditary predisposition genes accounts for near 40% of all cases. This proposal investigates the function of ELP1, a novel hereditary predisposition gene in SHH-medulloblastoma. ELP1 encodes the scaffolding member of the Elongator complex, which is involved in tRNA modification and efficient translation, but its role in tumorigenesis and cerebellum development is unknown. In this proposal, we will investigate the role of ELP1 in normal cerebellum development and determine how ELP1 loss predisposes patients to medulloblastoma. We will use a combination of mouse models, human induced pluripotent stem cell models, and molecular and cellular biology to uncover the conserved functions of ELP1, which may influence future patient treatment. Given its prevalence in SHH-medulloblastoma cases, our results may have the possibility to help many patients.

• DFG Programme: Research Grants