Detection in Fecal DNA of Colon Cancer–Specific Methylation of the Nonexpressed Vimentin Gene

• Published in: JNCI : Journal of the National Cancer Institute Vol. 97; no. 15; pp. 1124 - 1132
• Main Authors: Chen, Wei-Dong, Han, Z. James, Skoletsky, Joel, Olson, Jeff, Sah, Jerome, Myeroff, Lois, Platzer, Petra, Lu, Shilong, Dawson, Dawn, Willis, Joseph, Pretlow, Theresa P., Lutterbaugh, James, Kasturi, Lakshmi, Willson, James K. V., Rao, J. Sunil, Shuber, Anthony, Markowitz, Sanford D.
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 03.08.2005; Oxford Publishing Limited (England)
• Subjects: Adenocarcinoma - diagnosis; Adenocarcinoma - genetics; Adenoma - diagnosis; Adenoma - genetics; Biological and medical sciences; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Case-Control Studies; Cell Transformation, Neoplastic; Colorectal cancer; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - genetics; Deoxyribonucleic acid; Diagnostic tests; DNA; DNA Methylation; DNA, Neoplasm - analysis; Feces; Feces - chemistry; Gastroenterology. Liver. Pancreas. Abdomen; Genes; Genetic markers; Humans; Medical sciences; Occult Blood; Polymerase Chain Reaction; Reproducibility of Results; Sensitivity and Specificity; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Vimentin - genetics; Human; Vimentin; Biological marker; Malignant tumor; Molecular marker; Colonic disease; Colon cancer; Cancerology; Gene; DNA; Digestive diseases; Genetics; Intestinal disease; Diagnosis; Feces; Methylation
• ISSN: 0027-8874; 1460-2105; 1460-2105
• DOI: 10.1093/jnci/dji204

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.