Alimentary TractColorectal cancer screening by detection of altered human DNA in stool: Feasibility of a multitarget assay panel☆,☆☆,★
Section snippets
Design and subjects
The investigation was approved by the Mayo Clinic Institutional Review Board and comprised 2 clinical pilot studies. Stools for each were selected from a freezer archive to yield subject groups with verified colorectal adenocarcinoma, colorectal adenomas ≥1.0 cm, and colonoscopically normal colons. Subjects were chosen to provide a balanced age and gender representation across groups and a mixed distribution of neoplasms from both proximal and distal colorectal sites (Table 1).Most patients
Results
Analyzable human DNA was recovered in all subjects. When detected, mutant DNA accounted for 1%–24% of total human DNA recovered in stools from cancer patients and for 1%–7% from those with large adenomas.
Discussion
The rationale and appeal of stool screening for colorectal cancer would be strengthened if markers substantially more accurate than occult blood were used. On the basis of this pilot investigation, the aggregate assay of multiple genetic markers exfoliated into stool represents a promising alternative. The panel of neoplasm-associated DNA alterations targeted in this study highly discriminated patients with colorectal cancer or large adenomas from those with endoscopically normal colons.
The
Acknowledgements
The authors thank Drs. Bert Vogelstein and Kenneth W. Kinzler of Johns Hopkins University Oncology Center and Howard Hughes Medical Institute for helpful comments through the course of this study; Joy Yucaitis for extensive logistical support; Jaci McCormick, Mary Devens, Joel Swenson, and Nancy Diehl for valuable database support; Dr. Lawrence Burgart for pathology review; and Drs. Steven J. Laken and Barry Berger for contributions to technical aspects of assay interpretation and critical
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Address requests for reprints to: David Ahlquist, M.D., Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905. e-mail: [email protected]; fax: (507) 266-0350.
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Supported by grants from the National Cancer Institute of National Institutes of Health (R01 CA 7160), EXACT Laboratories (Maynard, MA), and Mayo Foundation (Rochester, MN) and by the philanthropic support of Charles W. Oswald.
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Mayo Foundation is a minor equity investor in EXACT Laboratories. D. Ahlquist is a member of EXACT Laboratories' Scientific Advisory Board but holds no stock and has received no consulting fees. J. Harrington and D. Mahoney have no affiliation with EXACT Laboratories. A. Shuber, J. Skoletsky, W. Pierceall, and K. Boynton are employees of EXACT Laboratories.