© 2005 Oxford University Press
ARTICLE |
Detection in Fecal DNA of Colon Cancer–Specific Methylation of the Nonexpressed Vimentin Gene
Affiliations of authors: Department of Medicine and Ireland Comprehensive Cancer Center, Case Western Reserve University, and University Hospitals of Cleveland, Cleveland, OH (W-DC, JS, LM, PP, SL, JKVW); Exact Sciences, Marlborough, MA (JS, ZJH, JO, AS); Department of Pathology and Ireland Comprehensive Cancer Center, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH (DD, JW, TPP); Department of Epidemiology and Biostatistics and Ireland Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH (JSR); Department of Medicine and Ireland Comprehensive Cancer Center, Case Western Reserve University and University Hospitals of Cleveland, and Howard Hughes Medical Institute, Cleveland, OH (JL, LK, SDM)
Correspondence to: Sanford Markowitz, MD, PhD, Case Western Reserve University, WRB 3-127, 10900 Euclid Ave., Cleveland, OH 44106-7285 (e-mail: sxm10{at}cwru.edu).
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 polymerase 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.
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- Fecal DNA Biomarkers for the Detection of Colorectal Neoplasia: Attractive, but Is It Feasible?
- Dean E. Brenner and Gad Rennert
J Natl Cancer Inst 2005 97: 1107-1109.[Extract] [Full Text] [PDF]
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