Molecular analysis of plasma DNA for the early detection of lung cancer by quantitative methylation-specific PCR

Kimberly Laskie Ostrow, Mohammad O. Hoque, Myriam Loyo, Marianna Brait, Alissa Greenberg, Jill M. Siegfried, Jennifer R. Grandis, Autumn Gaither Davis, William L. Bigbee, William Rom, David Sidransky

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69 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)3463-3472
Number of pages10
JournalClinical Cancer Research
Volume16
Issue number13
DOIs
Publication statusPublished - Jul 1 2010
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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