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Published on: September 25, 2011
Colorectal cancer screening by detection of altered human DNA in stool: feasibility of a multitarget assay panel
D A Ahlquist1, J E Skoletsky, K A Boynton
1Division of Gastroenterology and Hepatology, Department of Biostatistics, and Division of Molecular Genetics, Mayo Clinic, Rochester, Minnesota 55905, USA. ahlquist.david@mayo.edu
Background & Aims:
Assay of altered DNA exfoliated into stool represents an intriguing approach to screen for colorectal neoplasia, but multiple markers must be targeted because of genetic heterogeneity. We explored the feasibility of a stool assay panel of selected DNA alterations in discriminating subjects with colorectal neoplasia from those without.
Methods:
Freezer-archived stools were analyzed in blinded fashion from 22 patients with colorectal cancer, 11 with adenomas > or =1 cm, and 28 with endoscopically normal colons. After isolation of human DNA from stool by sequence-specific hybrid capture, assay targets included point mutations at any of 15 sites on K-ras, p53, and APC genes; Bat-26, a microsatellite instability marker; and highly amplifiable DNA.
Results:
Analyzable human DNA was recovered from all stools. Sensitivity was 91% (95% confidence interval, 71%-99%) for cancer and 82% (48%-98%) for adenomas > or =1 cm with a specificity of 93% (76%-99%). Excluding K-ras from the panel, sensitivities for cancer were unchanged but decreased slightly for adenomas to 73% (39%-94%), while specificity increased to 100% (88%-100%).
Conclusions:
Assay of altered DNA holds promise as a stool screening approach for colorectal neoplasia. Larger clinical investigations are indicated.
