Unravelling the impact of SMARCB1 loss on the chromatin landscape in malignant rhabdoid tumour to identify novel therapeutic opportunities
Lead investigator: Prof Maureen O'Sullivan, Trinity College Dublin
Funded July 2017 in partnership with the Children's Cancer and Leukaemia Group
Malignant rhabdoid tumour (MRT) is a very aggressive type of cancer and occurs primarily in young children, particularly in the first year of life. Despite being such an aggressive cancer, it is characterised by a single change in the genetic blueprint (DNA) whereby a particular gene is lost. Usually, five or six changes occur before cancer develops. How this single change leads to cancer, and especially such an aggressive cancer, is not understood. This project is designed to take a new approach to understanding what goes wrong in the cell when this gene is lost, leading to MRT developing.
It is known that the change in the DNA in MRT involves a particular gene which has a big role in the organisation of the DNA itself, and thereby acts like a 'master switch' in the cell, having a major impact. This project will study the organisation of the DNA in the cell, which will tell us a huge amount about what is driving the cancer. This will be done using a 'model system' of MRT in which we can selectively replace the genes that are lost to study how this impacts the organisation of the DNA. By comparing MRT lacking this key gene with our model that has the missing gene replaced, we will be able to see where there might be vulnerabilities in the tumour that could be exploited for the development of new drugs. At the same time, we will be examining what cell type MRT arises from, which is currently unknown, but has a real clinical importance as the treatment strategics for cancer must take into account the type of tissue or cell involved to improve outcomes.