Lymphangioleiomyomatosis (LAM) is a progressive and often fatal interstitial 
lung disease characterized by a diffuse proliferation of abnormal smooth muscle 
cells in the lungs. LAM is of unusual interest biologically because it affects 
almost exclusively young women. LAM can occur as an isolated disorder (sporadic 
LAM) or in association with tuberous sclerosis complex. Renal angiomyolipomas, 
which are found in most tuberous sclerosis patients, also occur in 60% of 
sporadic LAM patients. We previously found TSC2 loss of heterozygosity in 7 of 
13 (54%) of angiomyolipomas from sporadic LAM patients, suggesting that LAM and 
TSC could have a common genetic basis. In this study, we report the 
identification of somatic TSC2 mutations in five of seven angiomyolipomas from 
sporadic LAM patients. In all four patients from whom lung tissue was available, 
the same mutation found in the angiomyolipoma was present in the abnormal 
pulmonary smooth muscle cells. In no case was the mutation present in normal 
kidney, morphologically normal lung, or lymphoblastoid cells. Our data 
demonstrate that somatic mutations in the TSC2 gene occur in the angiomyolipomas 
and pulmonary LAM cells of women with sporadic LAM, strongly supporting a direct 
role of TSC2 in the pathogenesis of this disease.