BACKGROUND: Current approaches to the detection of colorectal neoplasia associated with inflammatory bowel disease (IBD-CRN) are suboptimal. AIM: To test the feasibility of using stool assay of exfoliated DNA markers to detect IBD-CRN. METHODS: This 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 IBD-CRNs 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. In the stool study, we evaluated candidate methylated genes (vimentin, EYA4, BMP3, NDRG4) in a prospective blinded study on buffered stools from 19 cases with known IBD-CRN and 35 age- and sex-matched IBD controls without CRN. From stool-extracted DNA, target genes were assayed using quantitative allele-specific real-time target and signal amplification method. RESULTS: IBD-CRN cases included 17 with ulcerative colitis (UC) and two with Crohn's disease (CD); nine had cancer and 10 had dysplasia. Controls included 25 with UC and 10 with CD. 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 IBD-CRN 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 (100%) of CRC and 80% of dysplasia, 4/4 (100%) of high grade and 4/6 (67%) of low grade. CONCLUSION: These findings demonstrate the feasibility of stool DNA testing for non-invasive detection of colorectal neoplasia associated with inflammatory bowel disease.
BACKGROUND: Current approaches to the detection of colorectal neoplasia associated with inflammatory bowel disease (IBD-CRN) are suboptimal. AIM: To test the feasibility of using stool assay of exfoliated DNA markers to detect IBD-CRN. METHODS: This 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 IBD-CRNs 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. In the stool study, we evaluated candidate methylated genes (vimentin, EYA4, BMP3, NDRG4) in a prospective blinded study on buffered stools from 19 cases with known IBD-CRN and 35 age- and sex-matched IBD controls without CRN. From stool-extracted DNA, target genes were assayed using quantitative allele-specific real-time target and signal amplification method. RESULTS: IBD-CRN cases included 17 with ulcerative colitis (UC) and two with Crohn's disease (CD); nine had cancer and 10 had dysplasia. Controls included 25 with UC and 10 with CD. 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 IBD-CRN 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 (100%) of CRC and 80% of dysplasia, 4/4 (100%) of high grade and 4/6 (67%) of low grade. CONCLUSION: These findings demonstrate the feasibility of stool DNA testing for non-invasive detection of colorectal neoplasia associated with inflammatory bowel disease.
Authors: Fumiaki Sato; David Shibata; Noam Harpaz; Yan Xu; Jing Yin; Yuriko Mori; Suna Wang; Andreea Olaru; Elena Deacu; Florin M Selaru; Martha C Kimos; Prodromos Hytiroglou; Joanne Young; Barbara Leggett; Adi F Gazdar; Shinichi Toyooka; John M Abraham; Stephen J Meltzer Journal: Cancer Res Date: 2002-12-01 Impact factor: 12.701
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Authors: Y Hirota; S Tanaka; K Haruma; M Yoshihara; K Sumii; G Kajiyama; F Shimamoto; N Kohno Journal: Oncol Rep Date: 2000 Mar-Apr Impact factor: 3.906
Authors: Fumiaki Sato; Noam Harpaz; David Shibata; Yan Xu; Jing Yin; Yuriko Mori; Tong-Tong Zou; Suna Wang; Kena Desai; Anatoly Leytin; Florin M Selaru; John M Abraham; Stephen J Meltzer Journal: Cancer Res Date: 2002-02-15 Impact factor: 12.701
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Authors: David H Johnson; William R Taylor; Mohammed M Aboelsoud; Patrick H Foote; Tracy C Yab; Xiaoming Cao; Thomas C Smyrk; Edward V Loftus; Douglas W Mahoney; David A Ahlquist; John B Kisiel Journal: Inflamm Bowel Dis Date: 2016-07 Impact factor: 5.325
Authors: John B Kisiel; Gauree G Konijeti; Andrew J Piscitello; Tarun Chandra; Thomas F Goss; David A Ahlquist; Francis A Farraye; Ashwin N Ananthakrishnan Journal: Clin Gastroenterol Hepatol Date: 2016-07-25 Impact factor: 11.382