Medulloblastoma is the most common malignant brain tumor in children. Its rapid growth and tendency to spread through the nervous system make it difficult to treat, and many of the children who develop the disease die from it. In addition, patients who survive medulloblastoma treatment often suffer cognitive deficits and have a tendency to develop other cancers later in life. Improved treatment of medulloblastoma is likely to come from a deeper understanding of the signals that control normal cerebellar development, and an appreciation of how these signals are dysregulated in tumors.

To identify such signals, we have studied an animal model of medulloblastoma -- the patched mutant mouse -- and screened for genes whose expression is altered in tumor cells compared to granule cell precursors, the cells from which the tumor is believed to arise (see Oliver et al., 2005). The genes whose expression changed most significantly included regulators of migration, apoptosis and differentiation, processes crucial for normal development but previously unrecognized for their role in medulloblastoma. Current studies in our lab are using retroviral gene transduction, cell transplantation and transgenic mice to elucidate the role of these genes in tumor initiation and progression.