BACKGROUND & AIMS: Fecal DNA testing has shown greater sensitivity than guaiac-based occult blood tests for noninvasive colorectal cancer (CRC) screening. The prototype assay (version 1), which analyzed 22 gene mutations and DNA integrity assay (DIA), showed a sensitivity of 52% for CRC detection and a specificity of 94% in average-risk individuals. The present study was conducted to determine the sensitivity and specificity of a second-generation assay (version 2) that uses improved DNA stabilization/isolation techniques and a new promoter methylation marker. METHODS: Forty patients with CRC and 122 subjects with normal colonoscopy provided stool samples to which DNA preservation buffer was added immediately. DNA was purified using gel-based capture, and analyzed for the original panel of 22 mutations, DIA, and 2 new promoter methylation markers. RESULTS: By using DNA that was optimally preserved and purified from stool, the sensitivity of the prototype version 1 assay increased to 72.5% because of enhanced performance of DIA. Vimentin gene methylation alone provided sensitivity and specificity of 72.5% and 86.9%, respectively. The optimal combination of vimentin methylation plus DIA resulted in 87.5% sensitivity and 82% specificity; cancers were detected regardless of stage or location. False-positive vimentin methylation was associated with older age. CONCLUSIONS: An improved fecal DNA test that incorporates only 2 markers shows much higher sensitivity for CRC. The new assay is easier to perform and should be less costly, thereby facilitating its use for noninvasive CRC screening.
BACKGROUND & AIMS: Fecal DNA testing has shown greater sensitivity than guaiac-based occult blood tests for noninvasive colorectal cancer (CRC) screening. The prototype assay (version 1), which analyzed 22 gene mutations and DNA integrity assay (DIA), showed a sensitivity of 52% for CRC detection and a specificity of 94% in average-risk individuals. The present study was conducted to determine the sensitivity and specificity of a second-generation assay (version 2) that uses improved DNA stabilization/isolation techniques and a new promoter methylation marker. METHODS: Forty patients with CRC and 122 subjects with normal colonoscopy provided stool samples to which DNA preservation buffer was added immediately. DNA was purified using gel-based capture, and analyzed for the original panel of 22 mutations, DIA, and 2 new promoter methylation markers. RESULTS: By using DNA that was optimally preserved and purified from stool, the sensitivity of the prototype version 1 assay increased to 72.5% because of enhanced performance of DIA. Vimentin gene methylation alone provided sensitivity and specificity of 72.5% and 86.9%, respectively. The optimal combination of vimentin methylation plus DIA resulted in 87.5% sensitivity and 82% specificity; cancers were detected regardless of stage or location. False-positive vimentin methylation was associated with older age. CONCLUSIONS: An improved fecal DNA test that incorporates only 2 markers shows much higher sensitivity for CRC. The new assay is easier to perform and should be less costly, thereby facilitating its use for noninvasive CRC screening.
Authors: Yuriko Mori; Alexandru V Olaru; Yulan Cheng; Rachana Agarwal; Jian Yang; Delgermaa Luvsanjav; Wayne Yu; Florin M Selaru; Susan Hutfless; Mark Lazarev; John H Kwon; Steven R Brant; Michael R Marohn; David F Hutcheon; Mark D Duncan; Ajay Goel; Stephen J Meltzer Journal: Endocr Relat Cancer Date: 2011-07-04 Impact factor: 5.678
Authors: David A Ahlquist; Hongzhi Zou; Michael Domanico; Douglas W Mahoney; Tracy C Yab; William R Taylor; Malinda L Butz; Stephen N Thibodeau; Linda Rabeneck; Lawrence F Paszat; Kenneth W Kinzler; Bert Vogelstein; Niels Chr Bjerregaard; Søren Laurberg; Henrik Toft Sørensen; Barry M Berger; Graham P Lidgard Journal: Gastroenterology Date: 2011-11-04 Impact factor: 22.682
Authors: Helen Moinova; Rom S Leidner; Lakshmeswari Ravi; James Lutterbaugh; Jill S Barnholtz-Sloan; Yanwen Chen; Amitabh Chak; Sanford D Markowitz; Joseph E Willis Journal: Cancer Epidemiol Biomarkers Prev Date: 2012-02-07 Impact factor: 4.254