Promising Biomarker, Candidate Tumour Suppressor Gene Identified For Colorectal Cancer
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Promising Biomarker, Candidate Tumour Suppressor Gene Identified For Colorectal Cancer

BETHESDA, Md -- June 18, 2009 -- Researchers have identified a new candidate tumour suppressor gene in colorectal cancer and examined its use as a potential biomarker in stool samples, according to a study published online in the June 17 issue of the Journal of the National Cancer Institute.

Manon van Engeland, PhD, Department of Pathology, Maastricht University Medical Center, Maastricht, the Netherlands, and colleagues examined N-Myc downstream-regulated gene 4 (NDRG4) as a novel tumour suppressor and biomarker.

The researchers analyzed NDRG4 promoter methylation and expression in human colorectal cancer cell lines, noncancerous colon mucosa, and colorectal cancer tissue. Quantitative methylation-specific polymerase chain reaction was used to examine NDRG4 promoter methylation as a biomarker in fecal DNA from 75 patients with colorectal cancer and 75 control subjects.

The researchers found that NDRG4 promoter methylation was more prevalent in colorectal cancers than in noncancerous colon mucosa. Its mRNA and protein expression were decreased in colorectal cancer tissue compared with noncancerous colon mucosa. A methylation-specific polymerase chain reaction assay for NDRG4 promoter methylation in stool identified the presence of colorectal cancer in 53% of colorectal cancer cases and correctly categorized a subject as cancer free 100% of the time.

"In conclusion, to our knowledge, this is the first study to describe a tumour suppressor role for NDRG4 in cancer," the authors wrote. "Our data indicate that NDRG4 promoter methylation is potentially useful as a sensitive and specific noninvasive pre-selection modality for identifying individuals at risk for colorectal cancer for whom colonoscopy is recommended."

In an accompanying editorial, Gad Rennert, MD, Carmel Medical Center and Technion, Haifa, Israel, discusses the concept of molecular testing of stool for early detection of colorectal cancer and where such testing stands today.

"Genetic diagnosis of colorectal cancers and meaningful adenomas has now reached a new phase that, when further fine-tuned, may carry the promise of becoming a suitable and affordable means of prevention and early detection of colorectal cancer in the general population," he wrote.

SOURCE: Journal of the National Cancer Institute

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