By taking advantage of subgroup-specific SHH, WNT, and Group 3 mouse cancer stem cell (CSC) lines that others and we isolated by the NeuroSphere assay from different subtypes of mouse MB (17, 18, 25, 26), we report for the first time to our knowledge that mTOR hyperactivation in MB is causally and specifically involved in the acquisition of LC/A histology and in increased malignancy in a specific subset of human SHH MB; we also note that addiction to this pathway in these patients may represent a cancer-specific vulnerability to be taken advantage of therapeutically. This evidence concerns the gene SHH and cancer.