title: Spectral karyotyping detects chromosome damage in bronchial cells of smokers and patients with cancer.
abstract: BACKGROUND
  Lung cancer is a multistep process that is preceded and often accompanied by molecular cytogenetic lesions in benign bronchial epithelium, the precise character, extent and timing of which are not well defined.
  
  
  OBJECTIVE
  In this study we comprehensively defined molecular cytogenetic changes in bronchial cells that may precede lung carcinoma using spectral karyotyping (SKY).
  
  
  METHODS
  SKY was applied to cultured benign bronchial cells from 43 high-risk smokers without carcinoma, 14 patients with concurrent lung carcinoma, and 14 never-smoker healthy volunteers.
  
  
  RESULTS
  The proportion of cells displaying numeric or structural anomalies/total number of metaphase cells was calculated for each case and was referred to as the chromosomal abnormality index. Mean chromosomal abnormality indices were 15.8, 10.1, and 0.7% for patients with cancer, high-risk smokers, and never-smokers, respectively. Clonal abnormalities were found in 17 (40%) of the high-risk smokers without carcinoma and 7 (50%) of the patients with carcinoma, but in none of 14 (0%) never-smokers. Chromosomal gains observed by SKY were confirmed in interphase cultured cells or paraffin sections of biopsy specimens by fluorescence in situ hybridization in 11 of 13 cases for which appropriate probes were available. In 6 of 57 high-risk patients or those with carcinoma, identical clonal abnormalities were dispersed at multiple bronchial sites and were admixed with nonclonal cells.
  
  
  CONCLUSIONS
  Clonal and single-cell chromosomal abnormalities are frequent in benign bronchial epithelium during lung carcinogenesis, indicating that chromosomal missegregation and other chromosomal rearrangements occur before overt malignancy.
authors.affiliation: Department of Medicine, School of Medicine, University of Colorado, Denver Health Sciences Center, Denver, Colorado, USA.
authors.forename: Marileila
authors.initials: M
authors.lastname: Varella-Garcia
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Roger L
authors.initials: RL
authors.lastname: Powell
authors.forename: Fred R
authors.initials: FR
authors.lastname: Hirsch
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Kennedy
authors.forename: Robert
authors.initials: R
authors.lastname: Keith
authors.forename: York E
authors.initials: YE
authors.lastname: Miller
authors.forename: John D
authors.initials: JD
authors.lastname: Mitchell
authors.forename: Wilbur A
authors.initials: WA
authors.lastname: Franklin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D001980:Bronchi / Q000473:pathology; D016022:Case-Control Studies; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D020545:Respiratory Mucosa / Q000473:pathology; D012306:Risk; D012680:Sensitivity and Specificity; D012907:Smoking / Q000009:adverse effects; D032681:Spectral Karyotyping
chemical_list: D014408:Biomarkers, Tumor