Microsatellite instability in patients with chronic obstructive pulmonary disease

Spandidos, Demetrios A.; Ergazaki, M.; Hatzistamou, Julia; Kiaris, Hippokratis; Bouros, Demosthenes; Tzortzaki, Eleni G.; Siafakas, Nikolaos M.

doi:10.3892/or.3.3.489

Cited by 15 publications

(17 citation statements)

References 15 publications

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“…The present authors have demonstrated genomic instability in the BL from a number of individuals with no clinical evidence of lung cancer, posing a question about exclusive occurrence of genomic instability in cancer. This observation was also supported by reports of genomic instability in nonmalignant diseases [117][118][119][120][121][122][123].…”

Section: Genomic Instabilitysupporting

confidence: 78%

The Liverpool Lung Project: a molecular epidemiological study of early lung cancer detection

Field¹,

Youngson²

2002

Eur Respir J

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Lung cancer is the major cause of death from neoplastic disease in the world, and even with politically-motivated smoking cessation campaigns throughout Europe, the disease remains the major cause of death. The development of molecular epidemiological population-based research into early lung cancer detection, such as the Liverpool Lung Project (LLP), may provide a way forward. This is the first major molecular epidemiological study of detection of early lung cancer.The use of molecular epidemiological risk assessments prior to clinical diagnosis and markers of preclinical carcinogenesis in patients with a high risk of developing lung cancer will reduce the incidence of clinically-detectable lung cancer, given the appropriate intervention strategies.The aims are as follows: 1) to prepare a molecular genetic and epidemiological risk assessment model based on environmental exposures and genetic predisposition; 2) to develop an archive of specimens relating to at-risk individuals and those with lung cancer; 3) to redefine lung cancer based on molecular pathology using the fields of expression profiling, genetic instability and molecular cytogenetics; 4) to identify and assess novel markers of precarcinogenesis in high-risk populations; and 5) to facilitate the development of new treatment strategies (e.g. chemoprevention programmes and targeted drug therapies).The LLP has two components: 1) a case-controlled study of newly-diagnosed cases of lung cancer that will provide a baseline, risk assessment; and 2) a prospective cohort study to be carried out over a 10-yr period that will identify markers of preclinical carcinogenesis. In-depth interviews are carried out using structured and semi-structured questionnaires. Sputum, blood and tumour specimens are collected and will be assessed for specific molecular markers (e.g. genetic instability, mutation and expression profiling, and methylation status).Conclusions from The Liverpool Lung Project will be based around molecularepidemiological and genotyping risk assessment models, as well as redefining the disease, and ultimately contributing to the development of new early lung cancer detection and treatment strategies.

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Section: Genomic Instabilitysupporting

confidence: 78%

The Liverpool Lung Project: a molecular epidemiological study of early lung cancer detection

Field¹,

Youngson²

2002

Eur Respir J

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“…Microsatellite DNA instability (MSI) has been initially reported in a number of human malignancies (5)(6)(7). During recent years such phenomena have also been detected in sputum cells of COPD patients, as well as in various other benign diseases (8)(9)(10)(11)(12). In addition, the detection of MSI in sputum cells of patients with COPD has been suggested to be disease specific in certain microsatellite markers, and could represent a useful marker of genetic susceptibility indicating destabilization of the genome at various loci (11).…”

Section: Introductionmentioning

confidence: 99%

Microsatellite DNA instability in nasal cytology of COPD patients

Karatzanis¹,

Samara²,

Tzortzaki³

et al. 2007

Oncol Rep

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Genetic alterations in the microsatellite DNA level have been successfully detected in sputum samples of patients with COPD and have been shown to be disease specific. Furthermore, previous studies have shown that inflammation coexists in the nasal mucosa of patients with COPD. The aim of this study was to assess the presence of MSI in nasal cytological samples of patients with COPD comparing the results with sputum samples of the same individuals. Nasal brush samples, sputum samples obtained by induction, and peripheral blood from 20 patients with COPD were analyzed. DNA was extracted and analyzed for MSI using the following microsatellite markers: RH70958, D5S207, D6S344, D6S263, G29802, D13S71, D14S588, D14S292 and D17S250. Microsatellite analysis was also performed in 8 healthy nonsmokers. MSI was detected in the sputum samples of 7 patients with COPD (35%). In contrast, no microsatellite DNA instability was noted in the nasal cytological samples of the same COPD patients. In addition, no genetic alteration was detected in the control group. These results suggest that MSI is a specific finding for the target organ of COPD, i.e. the lungs, despite the fact that inflammation coexists in the nasal mucosa of COPD patients. Our study supports the hypothesis that MSI could be an index of the somaticacquired genetic alterations in the lungs of COPD patients.

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“…Recent studies have shown that there are many genes with moderate effects in the pathogenesis of asthma rather than a few major ones. Chromosomal regions likely to harbour asthma susceptibility genes have been identified [8][9][10].…”

mentioning

confidence: 99%

Differences in microsatellite DNA level between asthma and chronic obstructive pulmonary disease

Zervou

Tzortzaki²,

Makris³

et al. 2006

Eur Respir J

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Previous studies have shown that microsatellite (MS) DNA instability (MSI) is detectable in sputum cells in chronic obstructive pulmonary disease (COPD) and asthma. The aim of the present study was to investigate whether asthma and COPD could be distinguished at the MS DNA level.DNA was extracted from sputum cells and white blood cells from 63 COPD patients, 60 non-COPD smokers, 36 asthmatics and 30 healthy nonsmokers. Ten MS markers located on chromosomes 2p, 5q, 6p, 10q, 13q, 14q and 17q were analysed.No MSI was detected in non-COPD smokers or healthy nonsmokers. A significantly higher proportion of COPD patients exhibited MSI (49.2%) compared to asthmatics (22.2%). MSI was detected even in the mild stages of COPD (33.3%) and asthma (22.2%). No relationship was found between MSI and COPD severity. The most frequently affected marker was D14S588 (17.5% in COPD and 2.7% in asthma). The markers D6S344, G29802 and D13S71 showed alterations only in COPD, and G29802 was associated with a significantly decreased forced expiratory volume in one second FEV1 (% predicted), whereas MSI in D6S344 was associated with a significantly higher FEV1 (% pred).The frequency of microsatellite instability was higher in chronic obstructive pulmonary disease than in asthma, and microsatellite instability in three workers showed chronic obstructive pulmonary disease specificity. However, further studies are needed to verify the differences between chronic obstructive pulmonary disease and asthma at the microsatellite level.

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Microsatellite instability in patients with chronic obstructive pulmonary disease

Cited by 15 publications

References 15 publications

The Liverpool Lung Project: a molecular epidemiological study of early lung cancer detection

The Liverpool Lung Project: a molecular epidemiological study of early lung cancer detection

Microsatellite DNA instability in nasal cytology of COPD patients

Differences in microsatellite DNA level between asthma and chronic obstructive pulmonary disease

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