Cancer-specific genomic instability in bronchial lavage: a molecular tool for lung cancer detection.
We examined genomic instability in DNA from 80 bronchial lavage samples from patients with lung cancer and individuals with no malignant lung disease. We used a multiplex assay of eight fluorescent-tagged microsatellite markers that have a very high incidence of allelic imbalance in lung tumors. When genomic instability at individual loci was analyzed statistically against diagnosis, markers D3S1289 (P = 0.033), D3S1300 (P = 0.001), D13S171 (P = 0.009), and D17S2179E (P = 0.017) demonstrated significantly higher frequency of instability in bronchial lavage specimens from lung cancer cases than those with nonmalignant conditions. In contrast, markers D9S157, D9S161, D13S153, and D5S644 demonstrated lower specificity (P > 0.05) for lung tumors. These results suggest that genomic instability in some loci may be related to high proliferation rates but not necessarily to cell commitment to malignancy. When genomic instability was scored with only the four cancer-specific markers, the assay produced a sensitivity of 73.9% and a specificity of 76.5%. On combining the results from the cytological examination and the molecular assay, the sensitivity reached 82.6%. These results indicate that in our efforts to investigate genomic instability as a potential marker for the early detection of lung cancer, we need to identify cancer-specific genomic instability markers. This paper has shown that these first four markers may be considered to form an individual set of cancer-specific genomic instability markers.
Roy Castle International Centre for Lung Cancer Research, Molecular Oncology Unit, Liverpool, United Kingdom.
T
T
Liloglou
P
P
Maloney
G
G
Xinarianos
M
M
Hulbert
M J
MJ
Walshaw
J R
JR
Gosney
L
L
Turnbull
J K
JK
Field
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D005260:Female; D005453:Fluorescence; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D004273:DNA, Neoplasm