title: Detection in fecal DNA of colon cancer-specific methylation of the nonexpressed vimentin gene.
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 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.
authors.affiliation: Department of Medicine, Ireland Comprehensive Cancer Center, Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH, USA.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Chen
authors.forename: Z James
authors.initials: ZJ
authors.lastname: Han
authors.forename: Joel
authors.initials: J
authors.lastname: Skoletsky
authors.forename: Jeff
authors.initials: J
authors.lastname: Olson
authors.forename: Jerome
authors.initials: J
authors.lastname: Sah
authors.forename: Lois
authors.initials: L
authors.lastname: Myeroff
authors.forename: Petra
authors.initials: P
authors.lastname: Platzer
authors.forename: Shilong
authors.initials: S
authors.lastname: Lu
authors.forename: Dawn
authors.initials: D
authors.lastname: Dawson
authors.forename: Joseph
authors.initials: J
authors.lastname: Willis
authors.forename: Theresa P
authors.initials: TP
authors.lastname: Pretlow
authors.forename: James
authors.initials: J
authors.lastname: Lutterbaugh
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Kasturi
authors.forename: James K V
authors.initials: JK
authors.lastname: Willson
authors.forename: J Sunil
authors.initials: JS
authors.lastname: Rao
authors.forename: Anthony
authors.initials: A
authors.lastname: Shuber
authors.forename: Sanford D
authors.initials: SD
authors.lastname: Markowitz
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics; D000236:Adenoma / Q000175:diagnosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000032:analysis*; D005243:Feces / Q000737:chemistry*; D006801:Humans; D009780:Occult Blood; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014746:Vimentin / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D014746:Vimentin