TSC1 and neoplasm: Conversely, upstream components of the mTOR pathway are frequently altered in human tumours (8,15), and UBC is not an exception, with reported mutations of phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha, AKT1 and tuberous sclerosis protein 1, hamartin, and loss of heterozygosity, homozygous deletion and inactivating mutations of phosphatase and tensin homologue deleted on chromosome 10 (39,40).