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Supervisor: Thomas Jacques, Darren Hargrave
Project Description:
Background:
Brain tumours are the most common cancer-related cause of death in children, and amongst survivors, there is a high risk of disability later in life. In many cases, the primary tumour can be treated, but if it recurs, there are few effective treatments and the outcomes are poor in many cases. We understand relatively little about the biology of late-stage disease, and what biological factors prevent effective treatment of recurrent disease.
One way to address this question is to understand the biological changes present as the disease progresses, particularly the biology of disease in fatal cases by studying tissue taken at autopsy. We have previously developed a set of samples from nearly 200 children who died of a brain tumour and have been able to undertake histological and genomic analysis of a high proportion of these tumours. In a separate study, we have analysed the changes in one particular tumour type over time in longitudinal samples. We found that over time, there was a change in the inflammatory tumour microenvironment.
Aims/Objectives:
In this project, the student will describe the changes in the tumour microenvironment over time and in different regions of the tumour at post-mortem. Specifically, they will test the hypothesis that late-stage disease is associated with a significant change in the tumour microenvironment.
Methods:
The student will build on the analysis we have undertaken on longitudinal samples (which uses a combination of histological and genomic techniques) to describe the tumour microenvironment over time and in different spatial locations in the autopsy cohort.
Timeline
Year 1: Training in the use of post-mortem tissue, immunohistochemistry and informatics. Immunohistochemical analysis of the tumour microenvironment in the autopsy cases.
Year 2: Further histological and genomic analysis of subsets of cases based on the preliminary data from year 1.
Year 3: Validation of findings and writing up.
References:
1. Stone T.J., …, Hargrave, D., Jacques, T.S. (2023) DNA methylation‐based classification of glioneuronal tumours synergises with histology and radiology to refine accurate molecular stratification Neuropathology and Applied Neurobiology 49(2):e12894. doi: 10.1111/nan.12894.
2. Stefan M … Alaggio, R. (2022) A Summary of the Inaugural WHO Classification of Pediatric Tumors: Transitioning from the Optical into the Molecular Era Cancer Discovery 2(2):331-355 doi: 10.1158/2159-8290.CD-21-1094.
3. Pickles, J.C., …, Jacques, T.S. (2020) The impact of molecular profiling on CNS tumour diagnosis and treatment: A paediatric population-based study The Lancet Child and Adolescent Health 4(2):121-130
4. 15. Stone T.J., … Hargrave, D., Jacques, T.S. (2023) DNA methylation‐based classification of glioneuronal tumours synergises with histology and radiology to refine accurate molecular stratification Neuropathology and Applied Neurobiology 49(2):e12894. doi: 10.1111/nan.12894
5. Stone, T.J., …, Jacques, T.S. (2018). Comprehensive molecular characterisation of epilepsy-associated glioneuronal tumours. Acta Neuropathologica, 135(1):115-129
Contact Information:
Tom Jacques