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Differential localization of hamartin and tuberin and increased S6 phosphorylation in a tuber

In a tuberous sclerosis patient with a mutation in the TSC1 tumor suppressor gene, no second-hit mutation was found in a resected cortical tuber. Tuber giant cells showed predominantly nuclear hamartin, cytosolic tuberin, and hyperphosphorylation of S6. Differential accumulation of hamartin and tuberin in separate cellular compartments of giant cells may prevent formation of the hamartin–tuberin complex, resulting in increased S6 phosphorylation. These data provide an alternative mechanism for tuberogenesis.