Molecular analysis of plasma DNA for the early detection of lung cancer by quantitative methylation-specific PCR.
OBJECTIVE
Aberrant promoter hypermethylation of tumor suppressor genes is a promising marker for lung cancer detection. We investigated the likelihood of detecting aberrant DNA methylation of tumor suppressor genes in plasma samples of patients with abnormalities of the lung detected upon computed tomography (CT) scan.


METHODS
In a small evaluation cohort, four gene promoters (DCC, Kif1a, NISCH, and Rarb) were found to be methylated with increased frequency in samples from cancer patients specifically. We then examined DNA from 93 plasma samples from patients with abnormal findings in the lung detected upon CT scan for aberrant methylation of these four gene promoters by quantitative fluorogenic real-time PCR. The patients were divided into two groups, ground glass opacity (n = 23) and cancerous tumors (n = 70). Plasma DNA from age-matched nodule-free individuals were used as controls (n = 80).


RESULTS
In plasma, 73% of patients with cancerous tumors showed methylation of at least one gene with a specificity of 71% (P = 0.0001). Only 22% patients with ground glass opacity exhibited methylation of at least one gene. When smoking history was taken into account, 72% of cancer patients with no smoking history or those who smoked <20 pack-years showed methylation of at least one gene with 100% specificity (P = 0.05) when compared with matched controls. Among heavy smokers with 20+ pack-years of smoking history, 30% of the control group and 73% of the patients with cancerous tumors showed methylation (P = 0.0001).


CONCLUSIONS
These biomarkers can distinguish between cancerous and noncancerous abnormal CT findings.
Ostrow
Kimberly Laskie
KL
Department of Otolaryngology-Head and Neck Cancer Research Division, Johns Hopkins School of Medicine, Baltimore, Maryland 21231, USA.
Hoque
Mohammad O
MO
Loyo
Myriam
M
Brait
Marianna
M
Greenberg
Alissa
A
Siegfried
Jill M
JM
Grandis
Jennifer R
JR
Gaither Davis
Autumn
A
Bigbee
William L
WL
Rom
William
W
Sidransky
David
D
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood*; D055088:Early Detection of Cancer; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D016133:Polymerase Chain Reaction / Q000379:methods*; D011401:Promoter Regions, Genetic; D012680:Sensitivity and Specificity; D012907:Smoking
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm