title: Genomic instability on hMSH2, hMLH1, CD48 and IRF4 loci in pulmonary sarcoidosis.
abstract: Pulmonary sarcoidosis shares certain features with immune disease and neoplasia, and microsatellite DNA alterations are detectable in sputum specimens of pulmonary sarcoidosis patients. The biological basis and significance of these findings remain obscure, while information regarding the genetic basis of the disease is limited. Using multiplex PCR-based microsatellite analysis, we investigated 40 markers located on 1p, 1q, 2p, 2q, 3p, 5q, 6p, 7p, 9p, 11q, 14q and 17p in 38 sputum specimens of pulmonary sarcoidosis patients. Loss of heterozygosity (LOH) was found in 13 of 38 (34.2%) patients in at least one locus. These alterations occurred in the subset of markers located in or close to DNA mismatch repair (MMR) genes, hMSH2 (2p22.3-p16.1) and hMLH1 (3p2l.32-p21.1), as well as in CD48 (1q21-q23) and IRF4 (6p23-p25), genes associated with lymphocyte activation. Microsatellite instability (MIN) was observed in five cases (13.2%) in at least one locus. Our data suggest that genomic instability in pulmonary sarcoidosis could be due to MMR defects, while alterations of lymphocyte-specific agents could account for granuloma formation.
authors.affiliation: Department of Virology, Medical School, University of Crete, University Hospital, Heraklion, Crete, Greece.
authors.forename: K
authors.initials: K
authors.lastname: Demopoulos
authors.forename: D A
authors.initials: DA
authors.lastname: Arvanitis
authors.forename: D A
authors.initials: DA
authors.lastname: Vassilakis
authors.forename: N M
authors.initials: NM
authors.lastname: Siafakas
authors.forename: D A
authors.initials: DA
authors.lastname: Spandidos
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD / Q000235:genetics*; D000071178:CD48 Antigen; D002352:Carrier Proteins; D000090266:Chromobox Protein Homolog 5; D002874:Chromosome Mapping; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D050835:Interferon Regulatory Factors; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D017565:Sarcoidosis, Pulmonary / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D000099218:Interferon Regulatory Factor-4
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D000071178:CD48 Antigen; D002352:Carrier Proteins; D000090266:Chromobox Protein Homolog 5; D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D000099218:Interferon Regulatory Factor-4; C000715594:CBX5 protein, human; C000604065:CD48 protein, human; C501486:MLH1 protein, human; C497172:MSH2 protein, human