Chromosome 16 loss of heterozygosity in tuberous sclerosis and sporadic lymphangiomyomatosis

In previous work we found loss of heterozygosity (LOH) of the wild-type TSC 2 allele in the abnormal pulmonary smooth muscle cells and renal angiomyoli poma cells from patients with sporadic pulmonary lymphangiomyomatosis (LAM) . Here we report TSC2 LOH in microdissected pulmonary LAM cells from a pati ent with tuberous sclerosis complex (TSC), demonstrating for the first time that the two-hit tumor suppressor gene model applies to the TSC-associated , as well as sporadic LAM. We also compared the chromosome 16 LOH region be tween angiomyolipoma and pulmonary LAM from two patients with sporadic LAM. Previously we found that these patients had TSC2 mutations and TSC2 LOH in their angiomyolipomas and pulmonary LAM cells but not in normal lung or ki dney cells. This suggests that pulmonary LAM may result from the migration of smooth muscle cells from renal angiomyolipomas to the lung. In this case , one would predict that the angiomyolipoma and LAM cells would have identi cal LOH patterns. We found that at each chromosome 16 marker, the results w ere concordant between angiomyolipoma and LAM. This is consistent with a mo del in which pulmonary LAM cells and angiomyolipoma cells have a common gen etic origin.