Detection in fecal DNA of colon cancer-specific methylation of the nonexpressed vimentin gene.
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.
Chen
Wei-Dong
WD
Department of Medicine, Ireland Comprehensive Cancer Center, Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH, USA.
Han
Z James
ZJ
Skoletsky
Joel
J
Olson
Jeff
J
Sah
Jerome
J
Myeroff
Lois
L
Platzer
Petra
P
Lu
Shilong
S
Dawson
Dawn
D
Willis
Joseph
J
Pretlow
Theresa P
TP
Lutterbaugh
James
J
Kasturi
Lakshmi
L
Willson
James K V
JK
Rao
J Sunil
JS
Shuber
Anthony
A
Markowitz
Sanford D
SD
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*
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D014746:Vimentin