Molecular Characterisation of Craniopharyngioma
Research type
Research Study
Full title
Molecular Characterisation of Human Craniopharyngioma
IRAS ID
169807
Contact name
Juan-Pedro Martinez-Barbera
Contact email
Sponsor organisation
University College London
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
Research Summary
Craniopharyngioma is a tumour of the pituitary gland and can affect children and adults. It often invades local structures leading to blindness, loss of critical hormones and severe obesity and early death. Current treatment is limited to surgery or radiotherapy, both of which also have severe side effects. There is an urgent need to better understand the biology of these tumours, so that new more specific treatments can be developed. This study will characterize the changes to DNA, mRNA and proteins within human craniopharyngioma specimens. This will be used to identify and characterize what molecular pathways are behind the tumours growth. This information will be used to correlate findings in and support and develop testing of novel therapies in a mouse model of craniopharyngioma and as a basis of studies of new treatments in human patients.
This broad project will involve contribute to the PhDs of several students within the host laboratory and be performed in collaboration with core facilities and established leaders in these techniques at UCL.Summary of Results
: In this project we studied the biology of craniopharyngioma, a challenging brain tumour which affects children, and also adults. In this project we characterised the DNA, RNA and Protein changes in tissue samples from solid and fluid (cystic) areas of tumour, to address controversies in the scientific literature and identify potential new treatments for patients. This data has also been analysed along side data from mouse models of the tumour and data from other groups of scientists working on this tumour type.
In this project we have:
1) Confirmed the presence of mutations in the gene CTNNB1 in all cases of adamantinomatous craniopharyngioma, and that the mutation is present in all the tumour epithelia (a type of cell)
2) Identified and characterised a close relationship between this tumour type and the developing tooth
3) Identified and characterised pathways activated in tumours including the MAPK pathway, Sonic Hedgehog pathway and inflammation
4) Characterised the presence of senescence in a group of tumour cells. These cells appear to drive tumour growth, and helped understand a process with relevance to other tumour types
5) Presented and published these results widely within the brain tumour community
6) Generated and deposited datasets useful to the community.
7) Developed a successor project to continue to develop and refine the findings of this project.REC name
London - Westminster Research Ethics Committee
REC reference
14/LO/2265
Date of REC Opinion
22 Dec 2014
REC opinion
Further Information Favourable Opinion