Original articlesAnalysis of promoter methylation in stool: A novel method for the detection of colorectal cancer
Section snippets
Patients and stool samples
The investigation was approved by the ethical committee of the Medical Faculty of the University of Munich. Stool samples were collected preoperatively from patients with verified CRCs (Table 1), and before endoscopy from patients with adenomas ≥1 cm (Table 2), endoscopically normal colons, hyperplastic polyps, and chronic inflammatory bowel disease (Table 3). Most patients with CRCs had been referred with a known diagnosis, all persons with adenomas and normal colons were asymptomatic and
Establishment of hypermethylated in cancer 1 promoter methylation analysis and determination of the sensitivity of the assay
DNA was extracted from microdissected tissues from primary CRCs, microdissected samples from normal colonic epithelium from individual patients, and peripheral blood leukocytes from healthy individuals. A nested MSP amplifying a CpG island within the HIC1 promoter 1b was established (Figure 1A). We found 7 of 9 cancers (78%) to contain both methylated and unmethylated and 2 cancers to contain unmethylated HIC1 DNA only (Figure 1B and data not shown). Furthermore, none of 8 samples from normal
Discussion
Highly sensitive, specific, and easily analyzable markers are required for noninvasive stool-based CRC screening. We show here that DNA methylation can be detected in stool of CRC patients with high specificity. The use of the DNA methylation marker, HIC1 promoter methylation, allowed for the highly specific detection of CRCs in 42% and of adenomas ≥1cm in 31% of cases. Interestingly, sensitivity was quite high for early cancers and higher for adenoma than FOBT. The combination of HIC1 MSP with
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Supported by the Sturm-Stiftung and the Bohnewand-Stiftung (to F.T.K.).
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K.L. and G.T.B. contributed equally to this work.