Microsatellite DNA instability and loss of heterozygosity in pulmonary sarcoidosis

In the present study we investigated the incidence of microsatellite instab ility (MI) and loss of heterozygosity (LOH) in sarcoidosis, a multisystem d isease of unknown origin. We examined sputum cytological specimens from 30 patients with sarcoidosis and 30 healthy, matched subjects, using 10 highly polymorphic microsatellite markers located at several chromosomal arms. Th e electrophoretic pattern of each specimen was compared with the correspond ing pattern of peripheral blood and any difference in the mobility of the m icrosatellite alleles was interpreted as Mt-positive. LOH was scored as dec rease in intensity of one allele relative to the other as determined from c omparison of sputum and normal (blood) DNA. We found that 14(47%) sarcoidos is patients showed genetic alterations, either MI or LOH. Six (20%) patient s exhibited MI and nine (30%) exhibited LOH in at least one microsatellite marker. One of the patients exhibited MI in two microsatellite markers and three (10%) showed LOH in more than one marker. One patient showed complete deletion of the chromosomal arm 17q11.2-q21. None of the healthy subjects exhibited any genetic alteration in the studied markers. No correlation was found between the genetic alterations detected and age, disease duration, blood gases, or spirometric parameters of the patients. Our findings sugges t that MI is a detectable phenomenon in sarcoidosis and seems not to be rel ated with the severity of the disease. The detection of LOH indicates the p resence of putative tumor suppressor genes at loci examined, which may play an important role in the etiopathogenesis of sarcoidosis.