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2002 
Of 134 faecal DNA samples analysed, 17 were found to have BAT26 alterations. Examples of the results from this assay are shown in the figure. All 17 faecal DNA samples yielding a positive BAT26 test were subsequently found to have been derived from patients with colorectal cancer (table). Among the cancer patients with proximal lesions, the clinical sensitivity of the BAT26 faecal DNA test was 37% (17 of 46 [95% CI 23–52]), with no positives among 69 individuals with normal colonoscopies or among 19 individuals with adenomas. The specificity was therefore 100% (95% CI 95–100). None of the patients in our cohort had variant BAT26 alleles in their germ line. 4 To determine the concordance of BAT26 alterations between faecal DNA and tumours, we microdissected neoplastic lesions from paraffin-embedded specimens of all 65 tumours (46 cancers plus 19 adenomas). DNA of adequate quality was recovered from 57 lesions, and 18 cases with BAT26 alterations were seen, all among cancers. 17 of these 18 cases corresponded to those with positive faecal tests, and in each of these cases, the size of the BAT26 alteration in tumour and faecal DNA was identical (figure). The results recorded above have several important implications for faecal DNA testing. First, they provide compelling evidence that mutations in faeces can be used to identify patients with cancer. The fact that 17 of the 18 cases with BAT26 mutations in their tumours gave rise to a positive faecal DNA test, coupled with the zero false-positive rate, was of particular note. Second, the results show that proximal cancers do not represent a barrier to faecal DNA analysis. Third, small samples of stool, rather than whole stools, could be analysed effectively, facilitating collection and storage of specimens for analysis. Finally, the proportion of mutant DNA molecules in faecal DNA ranged from 1·1% to 10·6%. Thus, techniques to assess faecal DNA mutations need be no more sensitive than this to detect most mutations. In the one sample that was a false negative, increasing the potential sensitivity five-fold by analysing an additional 2000 BAT26 genes in faecal DNA did not result in detection of the mutation. One practical application of these findings involves combination of BAT26 with sigmoidoscopy. Costeffectiveness modelling has indicated that sigmoidoscopy combined with unhydrated faecal occult blood tests can be more effective than colonoscopy for colorectal cancer screening. 1
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