Methylated vimentin in fecal DNA: a potential colon cancer biomarker
Last Updated: August 02, 2005



NEW YORK (Reuters Health) - Increased methylation of the vimentin
gene is a potential biomarker of colon cancer that can be detected in
fecal DNA to identify nearly half of adults with colon cancer,
researchers report.


The vimentin gene, which is transcriptionally silent in normal
colorectal epithelial cells, becomes methylated in colorectal
cancers, Dr. Sanford D. Markowitz from Case Western Reserve
University in Cleveland, Ohio, and colleagues explain in the in the
August 3rd issue of the Journal of the National Cancer Institute.

To see whether methylation of the vimentin gene could serve as a
biomarker for colon cancer, they compared methylation of this gene in
cancer tissues and in fecal DNA from colon cancer patients and normal
colon tissue samples from healthy subjects.

They detected aberrant vimentin methylation in 83% (38 of 46) and 53%
(57 of 107) of tumors from two independent groups of colon cancer
patients and in 46% (43 of 94) of fecal DNA from a third set of colon
cancer patients. In contrast, vimentin was unmethylated in 45 of 46
normal colon tissue samples.

When evaluated as a marker for colon cancer detection in fecal DNA
from another set of colon cancer patients, aberrant vimentin
methylation had a sensitivity of 46% and a specificity of 90% for
colon cancer.

It appears to be equally sensitive for detecting late stage and early
stage colorectal adenomas as well as proximal and distal cancers.

In comments to Reuters Health, Dr. Markowitz said: "This study shows
the potential for early detection of colon cancer by detecting
abnormally methylated DNAs in the feces of cancer patients. The
nearly 50% detection rate that we find with this first-generation
fecal DNA test is much superior to the 15% rate for detection of
colon cancer that is achieved by the classic test for detection of
occult blood in the stool," the researcher added.

"We believe that fecal DNA testing can achieve 90% or better rates of
colon cancer detection by combining our methylated DNA marker with
other colon cancer markers that are also detectable in stool," Dr.
Markowitz said. "A prospective clinical trial of such a fecal DNA
test panel is currently underway."

The co-authors of an editorial note that "the impact of adding
methylation biomarkers to mutation-based fecal DNA biomarkers remains
unknown."

"Nevertheless, we believe that a genetic methylation-based biomarker
panel should be pursued as part of a fecal DNA screening test for
colorectal neoplasia screening," write Drs. Dean E. Brenner from the
University of Michigan Cancer Center in Ann Arbor and Gad Rennert
from the Clalit Health Service National Israeli Cancer Control Center
in Haifa.