Chromosome 16 Loss of Heterozygosity in Tuberous Sclerosis and Sporadic Lymphangiomyomatosis

• Published in: American journal of respiratory and critical care medicine Vol. 164; no. 8; pp. 1537 - 1540
• Main Authors: YU, JANE, ASTRINIDIS, ARISTOTELIS, HENSKE, ELIZABETH PETRI
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 15.10.2001; American Lung Association
• Subjects: Biological and medical sciences; Chromosomes, Human, Pair 16 - genetics; Humans; Loss of Heterozygosity; Lymphangioleiomyomatosis - genetics; Medical sciences; Pneumology; Repressor Proteins - genetics; Respiratory system : syndromes and miscellaneous diseases; Tuberous Sclerosis - genetics; Tumor Suppressor Proteins; Human; Lung disease; Lymphangiomatosis; Nervous system diseases; Respiratory disease; Lung; Cardiovascular disease; Genetic determinism; Lymphatic vessel disease; Genetic disease; Tumor; Mutation; Bourneville syndrome; Chromosome 16
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/ajrccm.164.8.2104095

In previous work we found loss of heterozygosity (LOH) of the wild-type TSC2 allele in the abnormal pulmonary smooth muscle cells and renal angiomyolipoma cells from patients with sporadic pulmonary lymphangiomyomatosis (LAM). Here we report TSC2 LOH in microdissected pulmonary LAM cells from a patient 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 between 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 kidney 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 identical LOH patterns. We found that at each chromosome 16 marker, the results were concordant between angiomyolipoma and LAM. This is consistent with a model in which pulmonary LAM cells and angiomyolipoma cells have a common genetic origin.