Project 458969

Atypical Teratoid Rhabdoid Tumors (ATRTs) are rare brain tumors of young children under the age of 3. ATRTs tumours are unique in that they only lose one gene, SMARCB1, and have one of the lowest mutation rates across all cancers. Perplexingly, in spite of this quiet genome , ATRT patients respond differently to therapies, with only 40% of patients surviving after maximum intensity chemo- and radiation therapy. These treatments are often detrimental to the child and survivors often have long term developmental issues. There is a need to better understand the complex biology of this disease to develop more effective targeted therapies. Research from our lab examining large numbers of ATRTs showed they are made up of three different molecular types which correspond to different patient features including age of diagnosis, tumor location and sensitivity to certain drugs. The aim of my project is to understand why ATRT patients have different responses to treatment by applying an exciting new technology called Single Cell RNA Sequencing. This technology allows us to generate signatures from single tumor cells as well as from normal cells, such as immune cells, that infiltrate and make up the environment the tumor grows in. Data generated from these experiments will provide important new information regarding how tumor cells communicate with each other and the surrounding environment, which will help us understand tumor resistance and new ways to overcome it. My project will also apply the same methods to study and compare the features of human ATRT to a mouse model of ATRT in order to determine whether the different types of ATRTs come from different brain cells, and whether they have different growth requirements, which can be exploited for therapy. Work resulting from my project will provide new information about how to disrupt ATRT growth in a highly specific and targeted manner, and inform on development of novel therapies to improve survival of ATRT patients.