Abstract

We report on a 12-year-old female who developed osteosarcoma with tuberous sclerosis. Clinical sequencing of osteosarcoma tissues identified a somatic mutation in the TP53 gene and a novel germline mutation in the TSC2 gene. Pathological analysis of osteosarcoma tissue revealed increased phosphorylation of S6, a downstream target in the mTOR pathway. This is the first reported detection of a germline TSC2 mutation and somatic TP53 mutation in osteosarcoma with tuberous sclerosis. This case is unique and suggestive of a TSC2-dependent genetic pathway through mTOR signaling and a second-hit model for oncogenesis.