Metabolite profiles in the investigation of childhood brain tumours

Bennett, Christopher Daniel (2019). Metabolite profiles in the investigation of childhood brain tumours. University of Birmingham. Ph.D.

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Abstract

Paediatric brain tumours are the leading cause of cancer mortality in 0-14 year olds. New diagnostic and prognostic tools are required, as are new therapeutic targets to improve survival. Metabolism is a powerful characterising feature of tumours, with potential to aid the management of these diseases.

This thesis acquires metabolite profiles from paediatric brain tumour tissue, primarily by High Resolution Magic Angle Spinning NMR (HR-MAS), which are statistically analysed.

Firstly, metabolite profiles obtained by HR-MAS were shown to accurately and robustly classify tissue from the three main cerebellar tumours. When compared to current histological intraoperative testing, metabolites profiles correctly diagnosed histologically ambiguous tumours.

Secondly, survival analysis identified markers of prognosis. High glutamine concentration was associated with better clinical outcome both in terms of overall survival in a mixed tumour cohort and progression-free survival in a cohort of pilocytic astrocytomas.

Finally, metabolic pathway analysis identified pathways altered by cerebellar tumours relative to each other, supported with mass spectrometry and independent gene expression data. Pathways identified include alanine, aspartate and glutamate metabolism, taurine and hypotaurine metabolism and glycine, serine and threonine metabolism.

Considered together, this work provides strong reasoning for incorporating tissue metabolite profiles into clinical workflows for paediatric brain tumours.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):