Activation of mTORC1 in hamartoma syndromes and spontaneous tumors

In tumor cells of patients with congenital hamartoma syndromes such as Cowden syndrome (CS), tuberous sclerosis complex (TSC) syndrome and Peutz-Jeghers syndrome, the phosphatidylinositol 3-kinase (PI3K) and the mammalian target of rapamycin complex 1 (mTORC1) are overactivated. Major reasons for their dysregulation are inactivating mutations in tumor suppressor genes that code for PTEN, TSC1/TSC2 or LKB1, which are negative regulators of PI3K/mTORC1 signaling.