2013-02-19 14:27:00 UTC

Stool DNA Testing for the Detection of Colorectal Neoplasia in IBD

Feb. 21, 2013

Published ahead of print, a study by Kisiel, et. al in Alimentary Pharmacology & Therapeutics demonstrates the feasibility of stool DNA testing for the detection of colorectal neoplasia in patients with inflammatory bowel disease (IBD).

Current approaches to the detection of colorectal neoplasia associated with inflammatory bowel disease (IBD) are suboptimal. Dr. Kisiel and colleagues tested the feasibility of using stool assay of exfoliated DNA markers to detect IBD. The investigation comprised both tissue and stool studies.

In the tissue study, gene sequencing and methylation assays were performed on candidate genes using tissue DNA from 25 IBD and from 25 IBD mucosae without CRN. Mutations on p53, APC, KRAS, BRAF or PIK3CA genes were insufficiently informative, but several aberrantly methylated genes were highly discriminant. The researchers evaluated candidate methylated genes in a prospective blinded study on buffered stools from 19 cases with known IBD, and 35 age- and gender-matched IBD controls without CRN. From stool-extracted DNA, target genes were assayed using quantitative allele-specific real-time target and signal amplification method.

The doctors reported that IBD cases included 17 with ulcerative colitis, and two with Crohn's disease. The researchers found that nine had cancer, and 10 had dysplasia. Controls included 25 with ulcerative colitis, and 10 with Crohn's disease. Individually, BMP3, vimentin, EYA4 and NDRG4 markers showed high discrimination in stools with respective areas under the ROC curve of 0.9, 0.9, 0.85 and 0.84 for total IBD, and of 0.97, 0.97, 0.95 and 0.85 for cancer. The doctors noted that at 89 percent of specificity, the combination of BMP3 and mNDRG4 detected nine out of nine of colorectal cancer, and 80 percent of dysplasia, four out of four of high grade, and four out of six of low grade.

Dr Kisiel's team commented, "These findings demonstrate the feasibility of stool DNA testing for non-invasive detection of colorectal neoplasia associated with inflammatory bowel disease."

Alimentary Pharmacology & Therapeutics 2013: 37(5): 549-554

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