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Current approaches to the detection of colorectal neoplasia associated with inflammatory bowel disease are suboptimal. Dr Kisiel and colleagues tested the feasibility of using stool assay of exfoliated DNA markers to detect inflammatory bowel disease. The investigation comprised tissue and stool studies. In the tissue study, gene sequencing and methylation assays were performed on candidate genes using tissue DNA from 25 inflammatory bowel disease and from 25 inflammatory bowel disease 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 inflammatory bowel disease, and 35 age- and sex-matched inflammatory bowel disease controls without CRN. From stool-extracted DNA, target genes were assayed using quantitative allele-specific real-time target and signal amplification method.  | | The combination of BMP3 and mNDRG4 detected 9 out of 9 of colorectal cancer | | Alimentary Pharmacology & Therapeutics |
The doctors reported that inflammatory bowel disease cases included 17 with ulcerative colitis, and 2 with Crohn's disease. The researchers found that 9 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 inflammatory bowel disease, and of 0.97, 0.97, 0.95 and 0.85 for cancer. The doctors noted that at 89% of specificity, the combination of BMP3 and mNDRG4 detected 9 out of 9 of colorectal cancer, and 80% of dysplasia, 4 out of 4 of high grade, and 4 out of 6 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."
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