Germ line mutations of mutations in either TSC1 or TSC2 are found in 75-90% of cases of tuberous sclerosis complex (TSC), an autosomal dominant tumor syndrome associated with variable clinical phenotype including several hamrtomas and benign tumors. In addition, somatic alterations in these genes may occur in some tumor types. TSC1 and TSC2 both are tumor suppressor genes and their inactivation occurs by a classical two-hit mechanism. TSC1 is located on chromosome 9q34 and encodes hamartin. TSC2 is located on chromosome 16p13 and encodes tuberin. Hamartin and tuberin interact with and regulate a variety of proteins. These are negative regulators of the mTOR pathway, which is important for cell proliferation and frequently found activated in tumors. Mutation or deletion of TSC1 or TSC2 is found in 9-16 % of urothelial bladder tumors and up to 3% of clear cell renal cell carcinomas. More than 50% of bladder tumors of all grades and stages show LOH for markers on chromosome 9 and the TSC1 locus at 9q34 is a common critical region of deletion. Therefore, mTOR inhibitors have been identified as potential therapies for TSC1-mutated bladder cancers in some studies. LOH for the TSC1 or TSC2 locus has been described in 22% of 86 human lung cancer specimens. However, TSC1/2 sequence alterations are infrequent in lung and other epithelial malignancies.

This gene is a known cancer gene.

This gene is a known cancer gene.