Dr Nick Henriquez tells us about his research project on brain tumours.
Dr Nick Henriquez, working in the Division of Neuropathology at UCL Institute of Neurology, speaks of his teams’ research project on brain tumours:
“The research team have developed a model to test whether neural stem cells can cause brain cancer. These stem cells can self-renew: even in adults, they stay in the brain, divide and produce neurons. We have investigated the possibility that such stem cells can also turn rogue and form a brain tumour. We have tested that possibility experimentally, by turning on growth genes in these stem cells. We found that indeed stem cells can cause brain cancer.
Most strikingly, we found that we can predict the type of cancer depending on the type of growth signal we activate. A certain combination of genes (Rb and p53 gene loss) causes PNET, malignant brain tumours similar to medulloblastoma. Another combination (PTEN and p53 loss) induces gliomas, which are similar to the human glioblastoma, a malignant brain tumour in adults with poor prognosis.
The research focused on two aspects of the development of these experimental brain tumours:
- Is there a genetic and molecular “fingerprint” that defines a certain type of tumour? Because we can generate two types of tumour in the same model system, we are now interested in finding out what actually makes them so different. We have used special chips on which thousands of different genes can be examined in a single experiment (so called expression microarrays) to analyse these brain tumours. We found that there are genes that are unique to one or the other form of brain of cancer. We will now deepen our analysis to identify which of the changes are most relevant to the cancer. This will give us a "short list" of potential new therapeutic, prognostic or diagnostic markers. These can and will be used to help future cancer research in humans.
- Can we establish a test system which can also be used for human brain tumours? One of the greatest challenges in the treatment of brain tumours is to identify effective treatment with drugs. Using a mouse model, we have now found a method to analyse the response of tumours to treatment. We have compared the primary tumours that develop in the model (similar to human brain tumours) and tumours derived from mouse stem cells (similar to human tumour cell lines). Using the microchips mentioned above, we found a very similar expression profile.
The similarity of the grafted and primary tumours is very encouraging to extend this approach to study human brain tumours. We will derive primary cells and cell lines from patient tumours (e.g. malignant gliomas) at the National Hospital of Neurology and Neurosurgery, and graft them on to special (immunosuppressed) mice which will not reject the human cells. If the human primary and transplanted tumours show the same similarity as the re-implanted mouse cells, this may significantly improve our ability to test cancer treatments in model systems”.