Both patients carried mutations involving the PI3K/mTOR pathway; genetic analysis of the exceptional responder's tumor revealed a truncating TSC2 mutation, resulting in loss of negative regulation of mTOR signaling (25), and the other patient had a mutation in NF1, a regulator of TSC2 and mTOR, and in PIK3CA and mTOR (9). The gene discussed is NF1; the disease is neoplasm.