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Dr Kisiel and colleagues tested the feasibility of using stool assay of exfoliated DNA markers to detect colorectal neoplasia associated with inflammatory bowel disease.
This investigation comprised tissue and stool studies.
The team performed gene sequencing and methylation assays on candidate genes using tissue DNA from 25 colorectal neoplasia associated with inflammatory bowel disease, and from 25 IBD mucosae without colorectal neoplasia.
Mutations on p53, APC, KRAS, BRAF or PIK3CA genes were insufficiently informative, but several aberrantly methylated genes were highly discriminant.
The research team evaluated candidate methylated genes in a prospective blinded study on buffered stools from 19 cases with known colorectal neoplasia associated with inflammatory bowel disease, and 35 age- and sex-matched IBD controls without colorectal neoplasia.
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| The combination of BMP3 and mNDRG4 detected 80% of dysplasia |
| Alimentary Pharmacology & Therapeutics |
From stool-extracted DNA, target genes were assayed using quantitative allele-specific real-time target and signal amplification method.
The doctors examined that IBD-CRN cases included 17 with ulcerative colitis, and 2 with Crohn's disease.
The team found that 9 had cancer, and 10 had dysplasia.
Controls included 25 with ulcerative colitis, and 10 with Crohn's disease.
The team of doctors found that individually, BMP3, vimentin, EYA4 and NDRG4 markers showed high discrimination in stools with respective areas under the ROC curve of 0.91, 0.91, 0.85 and 0.84 for total colorectal neoplasia associated with inflammatory bowel disease, and of 0.97, 0.97, 0.95 and 0.85 for cancer.
At 89% specificity, the combination of BMP3 and mNDRG4 detected 9/9 of colorectal neoplasia and 80% of dysplasia, 4/4 of high grade and 4/6 of low grade.
Dr Kisiel's team concludes, "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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