title: Detection of loss of heterozygosity by high-resolution fluorescent system in non-small cell lung cancer: association of loss of heterozygosity with smoking and tumor progression.
abstract: BACKGROUND
  We recently developed a novel system for detecting microsatellite alteration, which is an important process in carcinogenesis. In patients with non-small cell lung cancer (NSCLC), loss of heterozygosity (LOH) is frequently observed and causes functional disorders of tumor suppressor genes.
  
  
  METHODS
  In a consecutive series of 51 patients with NSCLC who had undergone a surgical resection, microsatellite instability (MSI) and LOH in tumors were analyzed by polymerase chain reaction using five fluorescence-labeled dinucleotide markers (D2S123, D5S107, D10S197, D11SS904, and D13S175) and an autosequencer.
  
  
  RESULTS
  MSI was detected in only one patient (2.0%) with only one marker. LOH was detected in at least one chromosomal region that was tested in 39 patients (76%). The mean (+/- SD) number of LOHs detected by each marker was 1.74 +/- 1.40, with 1 LOH detected in 10 patients, 2 LOHs detected in 15 patients, 10 LOHs detected in 3 patients, 1 LOH detected in 4 patients, and 3 LOHs detected in 5 patients. The number of LOHs detected in each patient was significantly associated with the pack-year index (rho = 0.501; p = 0.0004), although there was no relationship with having a history of multiple cancers and familial cancer. Patients with stage IA disease showed a significantly lower number of LOHs than did patients with other stages of disease (1.15 vs 2.38, respectively; p = 0.0013).
  
  
  CONCLUSIONS
  LOH is very common in patients with NSCLC, and the number of LOHs increases with increases in smoking, suggesting the presence of an important event in lung carcinogenesis.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. iyoshino@surg2.med.kyushu-u.ac.jp
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yoshino
authors.forename: Seiichi
authors.initials: S
authors.lastname: Fukuyama
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Kameyama
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Shikada
authors.forename: Shinya
authors.initials: S
authors.lastname: Oda
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
authors.forename: Keizo
authors.initials: K
authors.lastname: Sugimachi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D005260:Female; D016153:Genes, Suppressor; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects