Colorectal cancer screening by detection of altered human DNA in stool: Feasibility of a multitarget assay panel

Background & Aims: Assay of altered DNA exfoliated into stool represents an intriguing approach to screen for colorectal neoplasia, but multiple marke rs must be targeted because of genetic heterogeneity. We explored the feasi bility of a stool assay panel of selected DNA alterations in discriminating subjects with colorectal neoplasia from those without. Methods: Freezer-ar chived stools were analyzed in blinded fashion from 22 patients with colore ctal cancer, 11 with adenomas greater than or equal to1 cm, and 28 with end oscopically normal colons. After isolation of human DNA from stool by seque nce-specific hybrid capture, assay targets included point mutations at any of 15 sites on K-ras, p53, and APC genes; Bat-26, a microsatellite instabil ity marker; and highly amplifiable DNA. Results: Analyzable human DNA was r ecovered from all stools. Sensitivity was 91% (95% confidence interval, 71% -99%) for cancer and 82% (48%-98%) for adenomas greater than or equal to1 c m with a specificity of 93% (76%-99%), Excluding K-ras from the panel, sens itivities 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 color ectal neoplasia. Larger clinical investigations are indicated.