title: Analysis of aberrant methylation on promoter sequences of tumor suppressor genes and total DNA in sputum samples: a promising tool for early detection of COPD and lung cancer in smokers.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) is a disorder associated to cigarette smoke and lung cancer (LC). Since epigenetic changes in oncogenes and tumor suppressor genes (TSGs) are clearly important in the development of LC. In this study, we hypothesize that tobacco smokers are susceptible for methylation in the promoter region of TSGs in airway epithelial cells when compared with non-smoker subjects. The purpose of this study was to investigate the usefulness of detection of genes promoter methylation in sputum specimens, as a complementary tool to identify LC biomarkers among smokers with early COPD.
  
  
  METHODS
  We determined the amount of DNA in induced sputum from patients with COPD (n = 23), LC (n = 26), as well as in healthy subjects (CTR) (n = 33), using a commercial kit for DNA purification, followed by absorbance measurement at 260 nm. The frequency of CDKN2A, CDH1 and MGMT promoter methylation in the same groups was determined by methylation-specific polymerase chain reaction (MSP). The Fisher's exact test was employed to compare frequency of results between different groups.
  
  
  RESULTS
  DNA concentration was 7.4 and 5.8 times higher in LC and COPD compared to the (CTR) (p < 0.0001), respectively. Methylation status of CDKN2A and MGMT was significantly higher in COPD and LC patients compared with CTR group (p < 0.0001). Frequency of CDH1 methylation only showed a statistically significant difference between LC patients and CTR group (p < 0.05).
  
  
  CONCLUSIONS
  We provide evidence that aberrant methylation of TSGs in samples of induced sputum is a useful tool for early diagnostic of lung diseases (LC and COPD) in smoker subjects.
  The abstract MUST finish with the following text: Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1127865005664160.
authors: Departamento de Bioquímica, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile. leda.guzman@ucv.cl
authors: Leda
authors: L
authors: Guzmán
authors: María Soledad
authors: MS
authors: Depix
authors: Ana María
authors: AM
authors: Salinas
authors: Rosa
authors: R
authors: Roldán
authors: Francisco
authors: F
authors: Aguayo
authors: Alejandra
authors: A
authors: Silva
authors: Raul
authors: R
authors: Vinet
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D004247:DNA / Q000032:analysis*; D019175:DNA Methylation / Q000235:genetics; D055088:Early Detection of Cancer / Q000379:methods*; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000235:genetics; D012907:Smoking / Q000009:adverse effects; D013183:Sputum / Q000737:chemistry*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004247:DNA