RT Journal Article
SR Electronic
T1 Molecular Analysis of Plasma DNA for the Early Detection of Lung Cancer by Quantitative Methylation-Specific PCR
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 3463
OP 3472
DO 10.1158/1078-0432.CCR-09-3304
VO 16
IS 13
A1 Ostrow, Kimberly Laskie
A1 Hoque, Mohammad O.
A1 Loyo, Myriam
A1 Brait, Marianna
A1 Greenberg, Alissa
A1 Siegfried, Jill M.
A1 Grandis, Jennifer R.
A1 Gaither Davis, Autumn
A1 Bigbee, William L.
A1 Rom, William
A1 Sidransky, David
YR 2010
UL http://clincancerres.aacrjournals.org/content/16/13/3463.abstract
AB Purpose: 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.Experimental Design: 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. Clin Cancer Res; 16(13); 3463–72. ©2010 AACR.