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Previous Volume 346:311-320 January 31, 2002 Number 5 Next

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ABSTRACT

Background Noninvasive methods for detecting colorectal tumors have the potential to reduce morbidity and mortality from this disease. The mutations in the adenomatous polyposis coli (APC) gene that initiate colorectal tumors theoretically provide an optimal marker for detecting colorectal tumors. The purpose of our study was to determine the feasibility of detecting APC mutations in fecal DNA with the use of newly developed methods.

Methods We purified DNA from routinely collected stool samples and screened for APC mutations with the use of a novel approach called digital protein truncation. Many different mutations could potentially be identified in a sensitive and specific manner with this technique.

Results Stool samples from 28 patients with nonmetastatic colorectal cancers, 18 patients with adenomas that were at least 1 cm in diameter, and 28 control patients without neoplastic disease were studied. APC mutations were identified in 26 of the 46 patients with neoplasia (57 percent; 95 percent confidence interval, 41 to 71 percent) and in none of the 28 control patients (0 percent; 95 percent confidence interval, 0 to 12 percent; P<0.001). In the patients with positive tests, mutant APC genes made up 0.4 to 14.1 percent of all APC genes in the stool.

Conclusions APC mutations can be detected in fecal DNA from patients with relatively early colorectal tumors. This feasibility study suggests a new approach for the early detection of colorectal neoplasms.

Source Information

From the Graduate Program in Human Genetics (G.T.), Howard Hughes Medical Institute (B.V.), and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (G.T., K.W.K., B.V.), Johns Hopkins School of Medicine, Baltimore; Exact Sciences, Maynard, Mass. (A.S., K.B.); the Division of Cancer Prevention (B.L.), the Department of Epidemiology (C.J.), and the Division of Pathology and Laboratory Medicine (S.R.H.), University of Texas M.D. Anderson Cancer Center, Houston; the Department of Surgery, Central Hospital, Västerås, Center for Clinical Research, Uppsala University, Uppsala, Sweden (L.O.); and the Department of Colon-Rectal Surgery, Lahey Clinic, Burlington, Mass. (D.J.S.).

Address reprint requests to Dr. Vogelstein at the Sidney Kimmel Comprehensive Cancer Center, 1650 Orleans St., Baltimore, MD 21231, or at vogelbe{at}welch.jhu.edu.

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Fecal DNA Tests for Colorectal Cancer
Ransohoff D. F., Traverso G., Kinzler K. W., Vogelstein B.
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N Engl J Med 2002; 346:1912-1913, Jun 13, 2002. Correspondence

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