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.
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 cancerpatients 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 cancerpatients 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.
Authors: Henning Usadel; Jan Brabender; Kathy D Danenberg; Carmen Jerónimo; Susan Harden; James Engles; Peter V Danenberg; Stephen Yang; David Sidransky Journal: Cancer Res Date: 2002-01-15 Impact factor: 12.701
Authors: M Esteller; A Sparks; M Toyota; M Sanchez-Cespedes; G Capella; M A Peinado; S Gonzalez; G Tarafa; D Sidransky; S J Meltzer; S B Baylin; J G Herman Journal: Cancer Res Date: 2000-08-15 Impact factor: 12.701
Authors: Shahnaz Begum; Mariana Brait; Santanu Dasgupta; Kimberly L Ostrow; Marianna Zahurak; André L Carvalho; Joseph A Califano; Steven N Goodman; William H Westra; Mohammad Obaidul Hoque; David Sidransky Journal: Clin Cancer Res Date: 2011-05-24 Impact factor: 12.531