Detection in fecal DNA of colon cancer-specific methylation of the nonexpressed vimentin gene

Wei Dong Chen, Z. James Han, Joel Skoletsky, Jeff Olson, Jerome Sah, Lois Myeroff, Petra Platzer, Shilong Lu, Dawn Dawson, Joseph Willis, Theresa P. Pretlow, James Lutterbaugh, Lakshmi Kasturi, James K.V. Willson, J. Sunil Rao, Anthony Shuber, Sanford D. Markowitz

Research output: Contribution to journalArticlepeer-review

296 Scopus citations

Abstract

Background: Increased DNA methylation is an epigenetic alteration that is common in human cancers and is often associated with transcriptional silencing. Aberrantly methylated DNA has also been proposed as a potential tumor marker. However, genes such as vimentin, which are transcriptionally silent in normal epithelium, have not until now been considered as targets for cancer-associated aberrant methylation and for use as cancer markers. Methods: We applied methylation-specific polymer ase chain reaction to the vimentin gene, which is transcriptionally silent in normal colonocytes, and compared methylation of vimentin exon 1 in cancer tissues and in fecal DNA from colon cancer patients versus control samples from healthy subjects. Results: Vimentin exon-1 sequences were unmethylated in 45 of 46 normal colon tissues. In contrast, vimentin exon-1 sequences were methylated in 83% (38 of 46) and 53% (57 of 107) of tumors from two independently collected groups of colon cancer patients. When evaluated as a marker for colon cancer detection in fecal DNA from another set of colon cancer patients, aberrant vimentin methylation was detected in fecal DNA from 43 of 94 patients, for a sensitivity of 46% (95% confidence interval [CI] = 35% to 56%). The sensitivity for detecting stage I and II cancers was 43% (26 of 60 case patients) (95% CI = 31% to 57%). Only 10% (20 of 198 case patients) of control fecal DNA samples from cancer-free individuals tested positive for vimentin methylation, for a specificity of 90% (95% CI = 85% to 94%). Conclusions: Aberrant methylation of exon-1 sequences within the nontranscribed vimentin gene is a novel molecular biomarker of colon cancer and can be successfully detected in fecal DNA to identify nearly half of individuals with colon cancer.

Original languageEnglish (US)
Pages (from-to)1124-1132
Number of pages9
JournalJournal of the National Cancer Institute
Volume97
Issue number15
DOIs
StatePublished - Aug 3 2005
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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