The importance of this question is underscored by the fact that activation of PI3K–Akt signalling (in PI3K catalytic subunit alpha [PIK3CA] constitutively active mutant or in PTEN inactivating mutant tumours) is a widespread cause of malignant human cancer, while activation of TORC1 (in TSC1 or TSC2 mutant tumours) causes benign hamartomas [75, 81]. This evidence concerns the gene TSC2 and neoplasm.