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

Kimberly Ostrow, Mohammad Hoque, Myriam Loyo, Mariana Brait Rodrigues De Oliveira, Alissa Greenberg, Jill M. Siegfried, Jennifer R. Grandis, Autumn Gaither Davis, William L. Bigbee, William Rom, David Sidransky

Research output: Contribution to journalArticle

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
StatePublished - Jul 1 2010

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Early Detection of Cancer
Methylation
Lung Neoplasms
Polymerase Chain Reaction
DNA
Tumor Suppressor Genes
Glass
DCC Genes
Neoplasms
Smoking
History
Tomography
Genes
Lung
DNA Methylation
Real-Time Polymerase Chain Reaction
Research Design

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Molecular analysis of plasma DNA for the early detection of lung cancer by quantitative methylation-specific PCR. / Ostrow, Kimberly; Hoque, Mohammad; Loyo, Myriam; Brait Rodrigues De Oliveira, Mariana; Greenberg, Alissa; Siegfried, Jill M.; Grandis, Jennifer R.; Davis, Autumn Gaither; Bigbee, William L.; Rom, William; Sidransky, David.

In: Clinical Cancer Research, Vol. 16, No. 13, 01.07.2010, p. 3463-3472.

Research output: Contribution to journalArticle

Ostrow, Kimberly ; Hoque, Mohammad ; Loyo, Myriam ; Brait Rodrigues De Oliveira, Mariana ; Greenberg, Alissa ; Siegfried, Jill M. ; Grandis, Jennifer R. ; Davis, Autumn Gaither ; Bigbee, William L. ; Rom, William ; Sidransky, David. / Molecular analysis of plasma DNA for the early detection of lung cancer by quantitative methylation-specific PCR. In: Clinical Cancer Research. 2010 ; Vol. 16, No. 13. pp. 3463-3472.
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N2 - 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

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